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2013-12-07T00:11:02Z

Yi11: /* Transition state properties of epoxidation */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Please note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|right|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

[[File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG|right|thumb|Jacobsen catalyst]]

The adjacent t-butyl group on the Jacobsen catalyst are arranged in a staggered manner to minimise steric repulsion as they are so close. Its crystal structure suggests a through space separation of 2.421 Â at the shortest contact and 2.975 Â for the longest. The steric bulk not only helps to stabilise the catalyst but increases the enantioselectivity of epoxidation as discovered by Palucki et al<ref>Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. "The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn-Catalyzed Epoxidation Reaction," ''J. Am. Chem. Soc.'' '''1998''', 120, 948–954.</ref>

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ Table 7. 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ Table 8. 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ Table 9. 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ Table 10. 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1
|}

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Chiroptical properties of the product epoxides====

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

The calculated ORD of this enantiomer is very close to that of the literature where 5 have been reported but give different values. Other solvents were used which will affect the rotatory power as the light can be diffracted differently depending on the solvent.

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform || 152.5 || 589 || chloroform
|}

The S,R ORD of was calculated to give the opposite rotation of the same magnitude however upon calculation of the R,S, a positive rotation matched that in literature.

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide {{DOI|10042/26685}}: [[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

1,2-dihydronapthalene oxide {{DOI|10042/26672}}: [[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || -3343.962162 || -3343.969197
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || -3383.251060 || -3383.259559
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

==Conclusion==

It was found that many programs can be used to predict properties of compounds using computer modelling to further understand reactions that we may not have otherwise been able to using other methods. Some still have drawbacks such as the QTAIM analysis only providing quantitative visual analysis however it will be exciting to see future developments leading it to perhaps widespread use.

==References==

<references />

Rep:Mod:yi111c

2013-12-07T00:06:38Z

Yi11: /* Conclusion */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Please note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|right|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

[[File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG|right|thumb|Jacobsen catalyst]]

The adjacent t-butyl group on the Jacobsen catalyst are arranged in a staggered manner to minimise steric repulsion as they are so close. Its crystal structure suggests a through space separation of 2.421 Â at the shortest contact and 2.975 Â for the longest. The steric bulk not only helps to stabilise the catalyst but increases the enantioselectivity of epoxidation as discovered by Palucki et al<ref>Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. "The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn-Catalyzed Epoxidation Reaction," ''J. Am. Chem. Soc.'' '''1998''', 120, 948–954.</ref>

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ Table 7. 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ Table 8. 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ Table 9. 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ Table 10. 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1
|}

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Chiroptical properties of the product epoxides====

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

The calculated ORD of this enantiomer is very close to that of the literature where 5 have been reported but give different values. Other solvents were used which will affect the rotatory power as the light can be diffracted differently depending on the solvent.

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform || 152.5 || 589 || chloroform
|}

The S,R ORD of was calculated to give the opposite rotation of the same magnitude however upon calculation of the R,S, a positive rotation matched that in literature.

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide {{DOI|10042/26685}}: [[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

1,2-dihydronapthalene oxide {{DOI|10042/26672}}: [[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

==Conclusion==

It was found that many programs can be used to predict properties of compounds using computer modelling to further understand reactions that we may not have otherwise been able to using other methods. Some still have drawbacks such as the QTAIM analysis only providing quantitative visual analysis however it will be exciting to see future developments leading it to perhaps widespread use.

==References==

<references />

Rep:Mod:yi111c

2013-12-07T00:00:35Z

Yi11: /* Assigning the absolute configuration of two epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Please note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|right|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

[[File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG|right|thumb|Jacobsen catalyst]]

The adjacent t-butyl group on the Jacobsen catalyst are arranged in a staggered manner to minimise steric repulsion as they are so close. Its crystal structure suggests a through space separation of 2.421 Â at the shortest contact and 2.975 Â for the longest. The steric bulk not only helps to stabilise the catalyst but increases the enantioselectivity of epoxidation as discovered by Palucki et al<ref>Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. "The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn-Catalyzed Epoxidation Reaction," ''J. Am. Chem. Soc.'' '''1998''', 120, 948–954.</ref>

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ Table 7. 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ Table 8. 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ Table 9. 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ Table 10. 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1
|}

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Chiroptical properties of the product epoxides====

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

The calculated ORD of this enantiomer is very close to that of the literature where 5 have been reported but give different values. Other solvents were used which will affect the rotatory power as the light can be diffracted differently depending on the solvent.

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform || 152.5 || 589 || chloroform
|}

The S,R ORD of was calculated to give the opposite rotation of the same magnitude however upon calculation of the R,S, a positive rotation matched that in literature.

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide {{DOI|10042/26685}}: [[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

1,2-dihydronapthalene oxide {{DOI|10042/26672}}: [[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T23:59:22Z

Yi11:

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Please note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|right|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

[[File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG|right|thumb|Jacobsen catalyst]]

The adjacent t-butyl group on the Jacobsen catalyst are arranged in a staggered manner to minimise steric repulsion as they are so close. Its crystal structure suggests a through space separation of 2.421 Â at the shortest contact and 2.975 Â for the longest. The steric bulk not only helps to stabilise the catalyst but increases the enantioselectivity of epoxidation as discovered by Palucki et al<ref>Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. "The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn-Catalyzed Epoxidation Reaction," ''J. Am. Chem. Soc.'' '''1998''', 120, 948–954.</ref>

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ Table 7. 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ Table 8. 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ Table 9. 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ Table 10. 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1
|}

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Chiroptical properties of the product epoxides====

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

The calculated ORD of this enantiomer is very close to that of the literature where 5 have been reported but give different values. Other solvents were used which will affect the rotatory power as the light can be diffracted differently depending on the solvent.

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform || 152.5 || 589 || chloroform
|}

The S,R ORD of was calculated to give the opposite rotation of the same magnitude however upon calculation of the R,S, a positive rotation matched that in literature.

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide {{DOI|10042/26685}}: [[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

1,2-dihydronapthalene oxide {{DOI|10042/26672}}: [[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T23:56:35Z

Yi11: /* Analysis of the Properties of Synthesised Alkene Epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|right|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

[[File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG|right|thumb|Jacobsen catalyst]]

The adjacent t-butyl group on the Jacobsen catalyst are arranged in a staggered manner to minimise steric repulsion as they are so close. Its crystal structure suggests a through space separation of 2.421 Â at the shortest contact and 2.975 Â for the longest. The steric bulk not only helps to stabilise the catalyst but increases the enantioselectivity of epoxidation as discovered by Palucki et al<ref>Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. "The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn-Catalyzed Epoxidation Reaction," ''J. Am. Chem. Soc.'' '''1998''', 120, 948–954.</ref>

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ Table 7. 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ Table 8. 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ Table 9. 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ Table 10. 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1
|}

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Chiroptical properties of the product epoxides====

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

The calculated ORD of this enantiomer is very close to that of the literature where 5 have been reported but give different values. Other solvents were used which will affect the rotatory power as the light can be diffracted differently depending on the solvent.

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform || 152.5 || 589 || chloroform
|}

The S,R ORD of was calculated to give the opposite rotation of the same magnitude however upon calculation of the R,S, a positive rotation matched that in literature.

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide {{DOI|10042/26685}}: [[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

1,2-dihydronapthalene oxide {{DOI|10042/26672}}: [[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

==Conclusion==

==References==

<references />

File:Yi11Jacobsen cat crystal tBu labelsinteractions.PNG

2013-12-06T23:07:15Z

Yi11:

File:Yi11Shi cat crystal labels.PNG

2013-12-06T23:06:58Z

Yi11: uploaded a new version of "File:Yi11Shi cat crystal labels.PNG": Reverted to version as of 22:35, 6 December 2013

File:Yi11Shi cat crystal labels.PNG

2013-12-06T23:06:41Z

Yi11: uploaded a new version of "File:Yi11Shi cat crystal labels.PNG"

Rep:Mod:yi111c

2013-12-06T23:04:45Z

Yi11: /* Analysis of the properties of synthesised alkene epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

==Analysis of the Properties of Synthesised Alkene Epoxides==

===Crystal structures of the Shi and Jacobsen catalysts ===

[[File:Yi11Shi cat crystal labels.PNG|thumb|Shi catalyst]]

The Shi catalyst has three anomeric centres. The C-O bond lengths come in pairs of one short, one longer as shown in Table 6. Taking C(10) as an example, C(10)-O(5) bond is shorter than the C(10)-O(4) as the O(5) acts as the electron donating group by lone pair donation into the empty σ* orbital of C(10)-O(4), increasing the bond length. it is most interesting to see O(2) acting as both the electron donating and accepting counterparts of two anomeric centres without much differentiation particularly to C(9). C-O bond lengths at C(2) anomeric centre are much shorter due to the favoured anti-periplanar arrangement of the lone pair and σ* creating a stronger interacting and shorter bond.

{| class="wikitable" border="1"
|+ Table 6. C-O bond lengths
! Anomeric centre !! Bond length A !! Bond length B
|-
| C(9) || 1.423 || 1.454
|-
| C(2) || 1.415 || 1.423
|-
| C(10) || 1.428 || 1.456
|}

m Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T22:46:44Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ Table 5. 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

File:Yi11Shi cat crystal labels.PNG

2013-12-06T22:35:48Z

Yi11:

Rep:Mod:yi111c

2013-12-06T22:25:57Z

Yi11: /* Spectroscopic Simulation using Quantum Mechanics */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm. The experimental value of δ = 74.61 ppm at Carbon-3 is much lower than predicted, caused by the spin-orbit coupling of sulfur to which it is adjacent. No correction value is available at present however considering that for C-Cl it is -3 ppm and -12 ppm for C-Br a value theoretically between the two will not make up for the -18.66 ppm discrepancy.

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T22:16:58Z

Yi11: /* Spectroscopic Simulation using Quantum Mechanics */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>. Paquette has noted that the methyl substituent α to the C=O carbonly group is brought closer to the bridgehead methyl groups in this conformation which opposes what is expected in terms of a steric argument. The vdW energy is lower still due to the overiding factor of the C=O being tucked under the main ring.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

(Note that the literature values do not correspond to the hydrogen number.) The 1H NMR data shows that the assignments by Paquette are consistent at higher chemical shifts in terms upon inspection of the range covered and the number of atoms they have been assigned to. At the lower end, greater deviations are seen perhaps to the dimethyl protons on the methyl bridge. More information of splitting and spin-spin coupling constants is required to conclude whether the literature has correctly assigned the peaks.

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 12 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The deviation plot of the 13C NMR data shows that the chemical shifts have been assigned relatively closely to those calculated with a mean deviation of around -3 ppm, with The experimental value of δ = 74.61 ppm is much lower than predicted, either caused by an error in the computation/optimisation of the initial structure or the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

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</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG

2013-12-06T22:15:38Z

Yi11: uploaded a new version of "File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG"

Rep:Mod:yi111c

2013-12-06T21:39:10Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Model values - Lit. values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 12 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 17 || 24.17 || 21.39 || -2.78
|-
| 18 || 24.57 || 22.21 || -2.36
|-
| 3 || 26.51 || 25.35 || -1.16
|-
| 2 || 28.42 || 25.56 || -2.85
|-
| 14,1 || 32.58 || 30.00 || -2.58
|-
| 19 || 33.72 || 35.47 || 1.75
|-
| 4 || 38.73 || 36.78 || -1.95
|-
| 9 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 6 || 45.80 || 43.28 || -2.52
|-
| 13 || 48.11 || 45.53 || -2.58
|-
| 22 || 49.67 || 50.94 || 1.27
|-
| 11 || 55.03 || 51.30 || -3.73
|-
| 16 || 65.94 || 60.53 || -5.41
|-
| 24 || 93.27 || 74.61 || -18.66
|-
| 15 || 120.22 || 120.90 || 0.68
|-
| 5 || 148.01 || 148.72 || 0.71
|-
| 25 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the One must be aware that chemical shifts for

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T21:12:32Z

Yi11: /* Spectroscopic Simulation using Quantum Mechanics */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="wikitable" border="1"
|+ Table 4. Energies of Isomers 17 and 18 (MMFF94s)
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 || 100.46580
|}

Isomer 18 is the thermodynamic product of the two conformers, being lower in energy by 4.3 kcalmol-1 than Isomer 17 which is consistent with reports in literature<ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ Table 5. 1H NMR of Isomer 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum (Click to enlarge)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || 2.70-2.35 || m || 4
|-
| 33, 37 || 2.93 || 2.20-1.70 || m || 6
|-
| 43 || 2.81 || 1.58 || t, J = 5.4 Hz || 1
|-
| 23 || 2.55 || 1.50-2.00 || m || 3
|-
| 41 || 2.47 || 1.10 || s || 3
|-
| 28, 46 || 2.34 || 1.07 || s || 3
|-
| 26 || 2.28 || 1.03 || s || 3
|-
| 44, 40 || 2.00
|-
| 27, 42 || 1.85
|-
| 51 || 1.65
|-
| 38 || 1.58
|-
| 48, 30 || 1.51
|-
| 29 || 1.36
|-
| 47 || 1.30
|-
| 31, 52 || 1.22
|-
| 53, 50, 49 || 0.95
|-
| 45 || 0.62
|-
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the calculated 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18 (TMS B3LYP/6-31(d,p) Chloroform)<ref>Y.Ichinose|{{DOI|10042/26671}}</ref>
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 12 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 17 || 24.17 || 21.39 || -2.78
|-
| 18 || 24.57 || 22.21 || -2.36
|-
| 3 || 26.51 || 25.35 || -1.16
|-
| 2 || 28.42 || 25.56 || -2.85
|-
| 14,1 || 32.58 || 30.00 || -2.58
|-
| 19 || 33.72 || 35.47 || 1.75
|-
| 4 || 38.73 || 36.78 || -1.95
|-
| 9 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 6 || 45.80 || 43.28 || -2.52
|-
| 13 || 48.11 || 45.53 || -2.58
|-
| 22 || 49.67 || 50.94 || 1.27
|-
| 11 || 55.03 || 51.30 || -3.73
|-
| 16 || 65.94 || 60.53 || -5.41
|-
| 24 || 93.27 || 74.61 || -18.66
|-
| 15 || 120.22 || 120.90 || 0.68
|-
| 5 || 148.01 || 148.72 || 0.71
|-
| 25 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T20:48:21Z

Yi11: /* Atropisomerism in an Intermediate related to the Synthesis of Taxol */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="wikitable" border="1"
|+ Table 3. Atropisomers of Taxol (MMFF94s)
! Optimised Energies !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 || 60.55202
|}

Isomer 10 is lower in energy by ～10　kcalmol-1 than Isomer 9. Initial examination of the structure may lead to attributing that to the decrease in transannular strain by orientation of the C=O carbonyl pointing down on the opposite face of the methyl bridge. However investigation into "hyperstable" alkenes<ref name="Hyperstable">W. F. Maier, P. von Rague Schleyer, "Evaluation and Prediction of the Stability of Bridgehead Olefins", ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref> by Maier has revealed such olefins containing less strain compared to their parent hydrocarbon are slow to react due to the twisted cage-like structure. From a molecular orbital point of view, this reduces the π overlap i.e. the HOMO-LUMO.

''only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.
Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>''

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T19:37:07Z

Yi11: /* Cyclopentadiene dimer */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

''Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.''

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained conformer. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also interesting to see that the ring junction C-C bond (joining the 6- and 5- membered rings) is 1.563 Â in Isomer 3 and 1.549 Â in Isomer 4, highlighting the relaxation of ring strain upon hydrogenation of the cyclopentene ring. Whilst the electrostatic energies are similar as the composition of both molecules are the same, the aforementioned differences allow Isomer 4 to be lower in energy, therefore the thermodynamic product.

As for the kinetic product, one must examine more transition states of this reaction and to determine which conformer proceeds via the lower.

''The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours''

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T19:14:40Z

Yi11: /* Cyclopentadiene dimer */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1." border="1"
|+ Table 1. Optimisation Energies of Cyclopentadiene dimers (MMFF94s)
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

As discovered by _____ [Ref], and as Table 1 shows, the lower energy exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap. As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the transition state of the endo form. This could also explain the lower bnd energy of the endo product being the greatest contributor to its lower total energy.

[[File:Yi11Cyclopentadiene2 orbitals.png|right|thumb|Stabilising orbital interaction in the endo diastereomer of dicyclopentadiene.]]

Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of dicyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Table 2." border="1"
|+ Table 2. Optimisation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring which does not possess a double bond in addition to a methyl bridge. The difference in bond angles at the unhydrogenated C=C double bond (Isomer 3) and the hydrogenated C-C bond (Isomer 4) can be seen [[Media:Yi11Cyclopentadiene3 4 bondlengthsangles.png|here]] where it is 103 °as opposed to 107 °in the less strained. The major contribution maybe the torsional energy difference where the -CH2 hydrogens on the cyclopentane ring in Isomer 4 are gauche but are eclipsed in Isomer 3 which contributes again to the lowering of the total energy. It is also noting that the ring junction C-C (joining the 6- and 5- membered rings) is 1.563

Note that bond lengths are different at ring junction

The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

File:Yi11Cyclopentadiene3 4 bondlengthsangles.png

2013-12-06T19:00:50Z

Yi11:

File:Yi11Cyclopentadiene2 orbitals.png

2013-12-06T18:41:28Z

Yi11:

Rep:Mod:yi111c

2013-12-06T18:19:49Z

Yi11: /* Determination of the more stable atropisomer of taxol */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1. Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

As discovered by _____ [Ref], the exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the the transition state of the endo form. This could also explain the lower angle bending energy of the endo product being the greatest contributor to its lower total energy. ORBITAL ALIGN.

http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html

Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="table 2. Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)"
|-
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring whcih does not possess a double bond as well as a methyl bridge this

Note that bond lengths are different at ring junction

The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Atropisomerism===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|150px]] || [[File:Yi11taxol10.png|150px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T16:09:16Z

Yi11: /* Electronic topology (QTAIM) in the active-site of the reaction transition state */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1. Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

As discovered by _____ [Ref], the exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the the transition state of the endo form. This could also explain the lower angle bending energy of the endo product being the greatest contributor to its lower total energy. ORBITAL ALIGN.

http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html

Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="table 2. Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)"
|-
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring whcih does not possess a double bond as well as a methyl bridge this

Note that bond lengths are different at ring junction

The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

===Suggestion of an Epoxide to Investigate===

1-desoxyhypnophilin can be synthesised

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T15:50:14Z

Yi11: /* Cyclopentadiene dimer */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Table 1. Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

As discovered by _____ [Ref], the exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the the transition state of the endo form. This could also explain the lower angle bending energy of the endo product being the greatest contributor to its lower total energy. ORBITAL ALIGN.

http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html

Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="table 2. Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers (MMF94s)"
|-
! Optimised Energies!! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

All the relative contributions to the total energy are lower in Isomer 4 which is ~9kcalmol-1 lower in energy than Isomer 3. The str energy is lower due to the lower ring strain on the 6-membered ring whcih does not possess a double bond as well as a methyl bridge this

Note that bond lengths are different at ring junction

The objective of this part of the module is to establish on the basis of the results obtained from the molecular mechanics technique whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T14:56:55Z

Yi11: /* Isomers of dicyclopentadiene */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Energies !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

As discovered by _____ [Ref], the exo-diastreomer is the more thermodynamically stable product however the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction where the endo form has a lower transition state according to Hammonds Postulate, otherwise the more thermodynamically favourable exo conformer would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, which leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of the p-orbitals to align and interact with the empty p-orbitals at the "back" of the dieneophile. This through-space interaction stabilises the the transition state of the endo form. ORBITAL ALIGN.

http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T13:23:16Z

Yi11: /* Chiroptical properties of the product epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. Kiskis, "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || 35.86<ref>Y. Ichinose {{DOI|10042/26689}}</ref> || 589 || chloroform || 155.82<ref>Y. Ichinose {{DOI|10042/26760}}</ref> || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T11:58:37Z

Yi11: /* Hydrogenation of di-cyclopentadiene */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|right|thumb|Cyclopentadiene hydrogenation scheme]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl( pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide {{DOI|10042/26689}}
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent

|-
| Mechanistic Model || 35.86 || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T11:52:28Z

Yi11: /* Chiroptical properties of the product epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''a) Optical Rotatory Dispersion, ORD'''

{| class="wikitable" border="1"
|+ ORD of styrene epoxide {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl( pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat
|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

{| class="wikitable" border="1"
|+ ORD of 1,2-dihydronapthalene oxide {{DOI|10042/26689}}
! rowspan="2"|Method !! colspan="3"|(1S,2R) !! colspan="3"| (1R,2S)
|-
! [a]25D /° !! Wave length /nm || Solvent|| [a]25D /° !! Wave length /nm || Solvent

|-
| Mechanistic Model || 35.86 || 589 || chloroform
|-
| Experimental<ref name="ORD DHNO">L. Hui, L. Yan, Q. Jing, W. Zhong-Liu, L. Hui, Q. Jing, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B: Enzym.'','''2010''', ''67 (3-4)'', 236-241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref> || -38.8 || 589 || chloroform
|}

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
REF 10.1016/j.molcatb.2010.08.012 -38.8 deg Hui, Yan

(1R,2S) [Hs down]
energy 30.683kcal 128.468 kJ

'''c) Vibrational Circular Dichroism, VCD'''

styrene epoxide
VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

DHNO
VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T11:20:27Z

Yi11: /* Chiroptical properties of the product epoxides */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ ORD (589 nm) {{DOI|10042/26689}}
! Method !! [a]25D /° !! Wave length /nm || Solvent
|-
| Mechanistic Model || -30.40 || 589 || chloroform
|-
| Experimental<ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl( pyridine)cobaloximesl", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref> || -33.3 || 589 || neat

|}

http://pubs.acs.org/doi/abs/10.1021/ja00853a029 <ref name="ORD sty epox">F. R. Jensen , R. C. KiskisJ., "Study of the N-H···H-B Dihydrogen Bond Including the Crystal Structure of BH3NH3 by Neutron Diffraction", ''J. Am. Chem. Soc.'', '''1975''', ''97 (20)'', 5825-5831.{{DOI|10.1021/ja00853a029}}</ref>

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}} (1S,2R
[Alpha] ( 5890.0 A) = 35.86 deg °
-38.8 Lin, Hui; Liu, Yan; Qiao, Jing; Wu, Zhong-Liu; Lin, Hui; Qiao, Jing

Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes

J. Mol. Catal. B: Enzym., 2010 , vol. 67, # 3-4 p. 236 - 241

[Hs down] (1R,2S) energy 30.683kcal 128.468 kJ

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

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</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T10:38:10Z

Yi11: /* (1S,2R)-1,2-dihydronapthalene oxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

{| class="wikitable" border="1"
|+ 13C NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 4 || 135.39 || 137.1 || 1.71 || 1 || rowspan="4"| [[File:Yi11DHNO optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 5 || 130.37 || 132.9 || 2.53 || 1
|-
| 6 || 126.67 || 129.9 || 3.23 || 1
|-
| 2 || 123.79 || 128.8 || 5.01 || 1
|-
| 3 || 123.53 || 128.8 || 5.27 || 1 || '''Deviation of literature values from those calculated'''
|-
| 1 || 121.74 || 126.5 || 4.76 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 9 || 52.82 || 55.5 || 2.68 || 1
|-
| 10 || 52.19 || 53.2 || 1.01 || 1
|-
| 7 || 30.18 || 24.8 || -5.38 || 1
|-
| 8 || 29.06 || 22.2 || -6.86 || 1

|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T10:28:59Z

Yi11: /* (1S,2R)-1,2-dihydronapthalene oxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

{| class="wikitable" border="1"
|+ 1H NMR of 1,2-dihydronapthalene oxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count ||rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="DHNO NMR"/> !! Literature !! Calculated !! Literature
|-
| 15 || 7.62 || 7.44 || -0.18　|| d, ''J'' = 7 Hz || 1 || 1 || rowspan="3"| [[File:Yi11DHNO optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 12,13 || 7.39 || 7.33-7.21 || -0.12 || m || 2 || 2
|-
| 14 || 7.25 || 7.13 || -0.12 || d, ''J'' = 7 Hz || 1 || 1
|-
| 21 || 3.56 || 3.89 || 0.33 || d, ''J'' = 4 Hz || 1 || 1 || '''Deviation of literature values from those calculated'''
|-
| 20 || 3.48 || 3.77 || 0.29 || t, ''J'' = 4 Hz || 1 || 1 || rowspan="5"| [[File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 16 || 2.95 || 2.83-2.79 || -0.18 ||m || 1 || 1
|-
| 17 || 2.27 || 2.59-2.55 || 0.30 || m || 1 || 1
|-
| 18 || 2.21 || 2.49-2.41 || 0.24 || m || 1 || 1
|-
| 19 || 1.87 || 1.18-1.76 || -0.09 || m || 1 || 1
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

<ref name="DHNO NMR">M. W. C. Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham*, "Epoxide ring-opening and Meinwald rearrangement reactions of epoxides
catalyzed by mesoporous aluminosilicates", ''Org. Biomol. Chem.'', '''2009''', ''7'', 2559-2564. {{DOI|10.1039/B900719A}</ref>1HNMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:59:57Z

Yi11: /* (1S,2R)-1,2-dihydronapthalene oxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[File:Yi11DHNO optimised NMR 2 atom labels.PNG|thumb|Numbered atoms of 1,2-dihydronapthalene oxide for NMR discussion.]]

{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:56:20Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|right|thumb|Numbered atoms of Isomer 18 for NMR discussion.]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:55:09Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|thumb|Numbered atoms of styrene epoxide corresponding to NMR dicussion]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:50:20Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[image:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|right|200px|Numbered atoms of styrene epoxide corresponding to NMR sicussion | ]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="3" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10 || '''Deviation of literature values from those calculated'''
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|150px]]
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|200px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2 || '''Deviation of literature values from those calculated'''
|-
| 2 || 122.95 || 125.65 || 2.70 || 2 || rowspan="4"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG|150px]]
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:43:19Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum (Click to enlarge)
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="4" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|200px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1 || Deviation of experimental values from those calculated
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1 || rowspan="3"| [[File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG|200px]]
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Calculated
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="8"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|300px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2
|-
| 2 || 122.95 || 125.65 || 2.70 || 2
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:39:33Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="8" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="8" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="8"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|300px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2
|-
| 2 || 122.95 || 125.65 || 2.70 || 2
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:38:53Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="8" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature
|-
| 5 || 135.13 || 137.75 || 2.62 || 1 || rowspan="8"| [[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg|300px]]
|-
| 1 || 124.13 || rowspan="2" | 128.65 || 4.521 || 1
|-
| 3 || 123.41 || 5.24 || 1
|-
| 4 || 122.96 || 128.33 || 5.37 || 2
|-
| 2 || 122.95 || 125.65 || 2.70 || 2
|-
| 6 || 118.27 || 128.33 || 10.06 || 1
|-
| 7 || 54.06 || 52.51 || -1.55 || 1
|-
| 8 || 53.47 || 51.33 || -2.14 || 1
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG

2013-12-06T09:29:38Z

Yi11: uploaded a new version of "File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG"

File:Yi11DHNO optimised NMR 2 13CNMR deviation.PNG

2013-12-06T09:13:14Z

Yi11:

File:Yi11DHNO optimised NMR 2 1HNMR deviation.PNG

2013-12-06T09:13:13Z

Yi11:

File:Yi11styreneepoxide optimised NMR 2 13CNMR deviation.PNG

2013-12-06T09:13:13Z

Yi11:

File:Yi11styreneepoxide optimised NMR 2 1HNMR deviation.PNG

2013-12-06T09:13:12Z

Yi11:

Rep:Mod:yi111c

2013-12-06T09:10:33Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="6" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Calculated !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:05:37Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="4" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Calculated !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T09:05:11Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="10" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="4" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Calculated !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T01:55:08Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Calculated !! Literature<ref name="sty epox NMR" /> !! Literature !! Calculated !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="4" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Calculated !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T01:54:07Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count || rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="sty epox NMR" /> !! Literature !! Molecular Model !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5 || rowspan="4" | [[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|300px]]
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

<jmol>
<jmolApplet>
<title>Transition state in R,R Jacobsen epoxidation of styrene</title><color>white</color><size>200</size>
<script>isosurface color orange purple "images/b/bb/Yi11styrene_RR_Jacobsen_TS_NCI.cub.jvxl" translucent;</script>
<uploadedFileContents>Yi11styrene RR Jacobsen TS NCI.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T01:52:15Z

Yi11: /* (R)-Styrene epoxide */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

[[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|400px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! Splitting !! colspan="2" | Proton count
|-
! Molecular model !! Literature<ref name="sty epox NMR" /> !! Literature !! Molecular Model !! Literature
|-
| 13 || 7.51 || rowspan="4" | 7.35 || rowspan="2" | -0.16　|| rowspan="4" | m || rowspan="4" | 4 || rowspan="5"| 5
|-
| 10 || 7.51
|-
| 12 || 7.48 || -0.13
|-
| 11 || 7.45 || -0.10
|-
| 14 || 7.30 || 7.35 || -0.05 || rowspan="4" | NA || rowspan="4" | 1
|-
| 15 || 3.66 || 3.87 || -0.21 || rowspan="3" | 1
|-
| 17 || 2.54 || 3.16 || 0.04
|-
| 16 || 2.34 || 2.81 || 0.27
|-
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

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</jmolApplet>
</jmol>

Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />

Rep:Mod:yi111c

2013-12-06T01:29:44Z

Yi11: /* 13C NMR calculation of Isomer 18 */

==Cyclopentadiene dimer ==

Cyclopentadiene dimerises to afford two isomers; exo- and endo-dimer as shown in Isomer 1 and Isomer 2 respectively below.

===Isomers of dicyclopentadiene ===

{| class="Optimsation Energies of Cyclopentadiene dimers (MMFF94s)"
|-
! Optimised Values !! Isomer 1 (exo) !! Isomer 2 (endo)
|-
| || <jmol><jmolApplet><title>Isomer 1</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene1.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 2</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene2.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.54301 || 3.46743
|-
| Total angle bending energy /kcalmol-1 || 30.77268 || 33.19131
|-
| Total torsional energy /kcalmol-1 || -2.73103 || -2.94945
|-
| Total van der Waals energy /kcalmol-1 || 12.80164 || 12.35726
|-
| Total electrostatic energy /kcalmol-1 || 13.01367 || 14.18431
|-
| Total Energy /kcalmol-1 || 55.37344 || 58.19070
|}

Cyclopentadiene undergoes a Diel-Alder cycloaddition reaction in order to dimerise with itself. It is particularly famous for the fact that it exists as the dimer at room temperature and must be heated to obtain the monomer. DISCUSS values

As discovered by _____ [Ref], it is commonly known that even though the exo diastreomer is the more thermodynamically stable product, the kinetic endo-diastereomer is formed. This is due to kinetic control of the reaction otherwise the more thermodynamically favourable exo product would be seen. One can explain this phenomenon by considering frontier orbital theory. The HOMO of the cyclopentadiene acting as a the diene (Ψ2) is electron rich and the LUMO of the other acting as the dienophile (π* of one C=C double bond) is electron deficient, with leads to a smaller difference in energy and better overlap - unlike the alternative combination of the diene LUMO (Ψ3) with the dienophile HOMO (π) as shown in the DIAGRAM.

As the two molecules approach each other, one can see that the "spare" double bond dienophile has the correct symmetry of orbitals to align and interact with the orbitals at the "back" of the dieneophile. This through space interaction stabilises the endo form. ORBITAL ALIGN & MO DIAGRAM.

According to ___ rules, the kinetic form must have a lower transition state. This even though the Isomer 1 is the endo-cyclopentadine dimer. http://www.chemtube3d.com/Cycloaddition1.html http://www.chemtube3d.com/Diels-Alder%20-%20Endo%20and%20Exo.html
Using Avogadro or ChemBio3D, define the two products 1 and 2 and optimise their geometries using the MMFF94(s) force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

===Hydrogenation of di-cyclopentadiene ===

Mono-hydrogenation of the endo dimer (Isomer 2) gives Isomer 3 and Isomer 4 as shown below.

[[File:Yi11Cyclopentadiene hydrogenation scheme.png|400px]]

{| class="Optimsation Energies of Mono-hydrogenated Cyclopentadiene dimers"
|-
! Optimised Values !! Isomer 3 !! Isomer 4
|-
| || <jmol><jmolApplet><title>Isomer 3</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene3.cml</uploadedFileContents>
</jmolApplet></jmol> || <jmol><jmolApplet><title>Isomer 4</title><color>white</color>
<size>200</size><script>zoom 4;moveto 4 0 2 0 90 120;spin 2;</script>
<uploadedFileContents>Yi11Cyclopentadiene4.cml</uploadedFileContents>
</jmolApplet></jmol>
|-
| Total bond stretching energy /kcalmol-1 || 3.31190 || 2.82311
|-
| Total angle bending energy /kcalmol-1 || 31.93610 || 24.68539
|-
| Total torsional energy /kcalmol-1 || -1.46985 || -0.37833
|-
| Total van der Waals energy /kcalmol-1 || 13.63724 || 10.63721
|-
| Total electrostatic energy /kcalmol-1 || 5.11949 || 5.14702
|-
| Total Energy /kcalmol-1 || 50.44573 = 211.206 kJ/mol || 41.25749 = 172.737 kJ/mol
|}

The two products of hydrogenation 3 and 4 can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in 2 can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and electrostatic energy terms in terms of the relative stability of 3 and 4.

Estimated time for completion: < 2 hours

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==

===Determination of the more stable atropisomer of taxol===

{| class="Atropisomers of Taxol"
|-
! Optimised Values !! Isomer 9 !! Isomer 10
|-
| || [[File:Yi11taxol9.png|200px]] || [[File:Yi11taxol10.png|200px]]

|-
| Total bond stretching energy /kcalmol-1 || 7.67191 || 7.58759
|-
| Total angle bending energy /kcalmol-1 || 28.27862 || 18.80989
|-
| Total torsional energy /kcalmol-1 || 0.24018 || 0.21960
|-
| Total van der Waals energy /kcalmol-1 || 33.15286 || 33.28941
|-
| Total electrostatic energy /kcalmol-1 || 0.30130|| -0.05491
|-
| Total Energy /kcalmol-1 || 70.53753 = 295.327 kJ/mol || 60.55202 = 253.519 kJ/mol
|}

Using MMFF94s force-field to determine the most stable isomer 9 or 10, and to rationalise why the alkene reacts slowly (hint: read the literature on hyperstable alkenes![6].
Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations).

A key intermediate 9 or 10 in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette: <ref name="Isomer 9 and 10 in Taxol synthesis">S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', ''1991'' 319.{{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}</ref>

Hyperstable alkenes <ref name="Hyperstable alkenes">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''' ''103'' 1891.{{DOI|10.1021/ja00398a003}}</ref>

==Spectroscopic Simulation using Quantum Mechanics==

1H and 13C NMR of one of the two isomers of an intermediate related to the synthesis of taxol; Isomer 17 and Isomer 18 were calculated. The energies were calculated first and the more stable form used to obtain spectroscopic values as the lower is more stable and observable to give experimental values in literature for comparison.

{| class="Energies of Isomers 17 and 18"
|-
! Optimised Values !! Isomer 17 !! Isomer 18
|-
| || [[File:Yi11taxol17 .png|150px]] || [[File:Yi11taxol18 .png|150px]]
|-
| Total bond stretching energy /kcalmol-1 || 15.87430 || 15.01619
|-
| Total angle bending energy /kcalmol-1 || 31.46355 || 30.82548
|-
| Total torsional energy /kcalmol-1 || 11.24601 || 9.73773
|-
| Total van der Waals energy /kcalmol-1 || 51.96730 || 49.37303
|-
| Total electrostatic energy /kcalmol-1 || -7.29917 || -6.02965
|-
| Total Energy /kcalmol-1 || 104.75446 = 438.586 || 100.46580 = 420.63
|}

Isomer 18 is lower in energy by 4.3 kcalmol-1 than Isomer 17. The only structural difference is in the orientation of the C=O carbonyl pointing down on the opposite face of the bridge. This favourable arrangement is shown in the difference in torsional energy, being the greatest contributor to the overall lowering of energy.

The NMR spectrum was predicted with the B3LYP method, 6-31(d,p) basis set, chloroform solvation model and published here {{DOI|10042/26671}}.

===1H NMR calculation of Isomer 18===

{| class="wikitable" border="1"
|+ 1H NMR of Isomer 18
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count !! rowspan="2" | Spectrum
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" /> !! Literature !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 1HNMR spectrum small.svg| 300px]]
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

===13C NMR calculation of Isomer 18===

The technique for comparing the modeled 13C chemical shifts to those in the literature was taken from Braddock and Rzepa's<ref name="chemical shift comparison">C. Braddock and H. S. Rzepa, ''J. Nat. Prod.'', '''2008''', ''71'', 728-730.{{DOI|10.1021/np0705918}}</ref> investigation.

[[File:Yi11taxol18 numbered C.png|200px]]

{| class="wikitable" border="1"
|+ 13C NMR of Molecule 18
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm !! rowspan="2" | Δδ /ppm !! rowspan="2" | Spectrum

(Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="Spectroscopic data for Isomer 18" />
|-
| 25 || 22.59 || 19.83 || -2.76 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR spectrum.svg| 300px]]
|-
| 5 || 24.17 || 21.39 || -2.78
|-
| 15 || 24.57 || 22.21 || -2.36
|-
| 24 || 26.51 || 25.35 || -1.16
|-
| 16 || 28.42 || 25.56 || -2.85
|-
| 11 || 32.58 || 30.00 || -2.58
|-
| 22 || 33.72 || 35.47 || 1.75
|-
| 13 || 38.73 || 36.78 || -1.95
|-
| 6 || 41.35 || 38.73 || -2.62 || '''Deviation of literature values from those calculated'''

|-
| 8 || 44.16 || 40.82 || -3.34 || rowspan="7" | [[File:Yi11taxol18 optimised NMR 2 13CNMR deviation.PNG|300px]]
|-
| 9 || 45.80 || 43.28 || -2.52
|-
| 4 || 48.11 || 45.53 || -2.58
|-
| 19 || 49.67 || 50.94 || 1.27
|-
| 14,1 || 55.03 || 51.30 || -3.73
|-
| 2 || 65.94 || 60.53 || -5.41
|-
| 3 || 93.27 || 74.61 || -18.66
|-
| 18 || 120.22 || 120.90 || 0.68
|-
| 17 || 148.01 || 148.72 || 0.71
|-
| 12 || 213.05 || 211.49 || -1.56
|}

The 13C NMR data shows that the

Spectroscopic data for Isomer 18 <ref name="Spectroscopic data for Isomer 18">L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers, ''J. Am. Chem. Soc.'', '''1990''', ''112'', 277-283. {{DOI|10.1021/ja00157a043}}</ref>

===Comparison of the relative energies of the Isomer 17 and Isomer 18 ===

The NMR calculations report a free energy, G for which Isomer 17 is -1651.460770 kJmol-1 and Isomer 18 is -1651.464194 kJmol-1. The difference in energy of the two isomeric configurations, ΔG is -0.003424 kJmol-1 upon isomerisation from Isomer 17 to Isomer 18; Isomer 18 is the more stable configuration. This is consistent with the energies manifested from the optimisation of the structures using Avogadro, shown in the table above. Using the equation Δ<math>G = -RTlnK</math>, the equilibrium constant K = 1.00. (K=0.0265 if ΔG in Hartree)

==Analysis of the properties of synthesised alkene epoxides==

The Shi asymmetric Fructose catalyst : Conquest [NELQEA01]

The Jacobsen asymmetric catalyst [TOVNIB01]

===Crystal structures of the Shi and Jacobsen catalysts ===

Shi catalyst: Molecule 21

C-O bond lengths for anomeric centres (O-C-O motif)

For 21 analyse and discuss the C-O bond lengths for any anomeric centres (i.e. those with O-C-O substructures) using the Mercury program and any other interesting features you might discover.
For 23 analyse and discuss the close approach of the two adjacent t-butyl groups on the rings and any other interesting features you might discover.

===NMR properties of two synthesised epoxides===

You can compute the expected 13C and 1H spectra (chemical shifts and coupling constants) of your epoxides to check the integrity of what you have made. The technique for doing this was illustrated for taxol above. This on its own however will not identify the absolute configuration of your product.

====(R)-Styrene epoxide====

NMR chemical shifts {{DOI|10042/26679}} Spin-spin coupling {{DOI|10042/26680}} gNMR http://books.google.co.uk/books?id=-pn8K53IUqgC&printsec=frontcover#v=onepage&q=gnmr&f=false

[[File:Yi11styreneepoxide optimised NMR 2 atom labels.PNG|200px]]

[[File:Yi11styreneepoxide optimised NMR 2 1HNMR spectrum.svg|400px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! colspan="2" | Splitting !! colspan="2" | Proton count
|-
! Molecular model !! Literature<ref name="sty epox NMR" /> !! Molecular model !! Literature !! Molecular model !! Literature
|-
| || || || || ||
|-
| 35, 32 || 3.13 || || ||
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || ||
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 ||
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|}

[[File:Yi11styreneepoxide optimised NMR 2 13CNMR spectrum.svg| 400px]]

{| class="wikitable" border="1"
|+ 13C NMR of (R)-Styrene epoxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Lit. values - Model values)
|-
! Molecular model !! Literature<ref name="sty epox NMR" />
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
|}

https://www.thieme-connect.de/ejournals/html/10.1055/s-2007-965877 <ref name="sty epox NMR">Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN., ''J. Am. Chem. Soc.'', '''2002''', ''124'', 1307.{{DOI|10.1055/s-2007-965877}}</ref>
( R )-Styrene Oxide [( R )-7]

Colorless liquid; yield: 44 mg (37%); 87% ee [chiral GC analysis, chiral capillary column β-Hydrodex PM, 100 °C, isothermal, t R = 14.45 min (major), 15.13 min (minor)].

[α]D 20 +20.3 (c 0.3, CH2Cl2) {Lit. [8b] [α]D 23 +28.6 (neat)}. Schaus SE. Brandes BD. Larrow JF. Tokunada M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc. 2002, 124: 1307

1H NMR (400 MHz, CDCl3): δ = 2.81 (dd, J = 5.4, 2.5 Hz, 1 H, PhCHCHH), 3.16 (dd, J = 5.4, 4.0 Hz, 1 H, PhCHCHH), 3.87 (dd, J = 4.0, 2.5 Hz, 1 H, PhCHCH2), 7.30-7.40 (m, 5 H, Ph).

13C NMR (100 MHz, CDCl3): δ = 51.33, 52.51, 125.65, 128.33, 128.65, 137.75.

====(1S,2R)-1,2-dihydronapthalene oxide====

[[Mod:numbered structure of dhno ox| 500px]]
{{DOI|10042/26641}} TMS B3LYP/6-31G(d,p) Chloroform

[[File:1H NMMR spec dhno ox|500px]]

{| class="wikitable" border="1"
|+ 1H NMR of (R)-Styrene epoxide
! rowspan="2" | Hydrogen number !! colspan="2" | Chemical shift /ppm !! Splitting !! Proton count
|-
! Molecular model !! Literature [Ref] !! Literature [Ref] !! Literature
|-
| 20 || 5.99 || 5.21 || m || 1　|| 1
|-
| 35, 32 || 3.13 || 3.00-2.00 || m || 6
|-
| 34 || 3.00 || || ||
|-
| 33, 37 || 2.93 || || m || 4
|-
| 43 || 2.81 || || ||
|-
| 23 || 2.55 || || ||
|-
| 41 || 2.47 || || ||
|-
| 28, 46 || 2.34 || ||
|-
| 26 || 2.28 || || ||
|-
| 44, 40 || 2.00 || ||
|-
| 27, 42 || 1.85 || ||
|-
| 51 || 1.65 || ||
|-
| 38 || 1.58 || 1.58 || t, J = 5.4 Hz || 1
|-
| 48, 30 || 1.51 || ||
|-
| 29 || 1.36 || || ||
|-
| 47 || 1.30 || || ||
|-
| 31, 52 || 1.22 || ||
|-
| 53, 50, 49 || 0.95 || || ||
|-
| 45 || 0.62 || || ||
|-
| || || 2.20-1.70 || m || 6
|-
| || || 1.50-2.00 || m || 3
|-
| || || 1.10 || s || 3
|-
| || || 1.07 || s || 3
|-
| || || 1.03 | s | 3
|}

[[File:13C nmr spec dhno ox| 500px]]

{| class="wikitable" border="1"
|+ 13C NMR of (1S,2R)-1,2-dihydronapthalene oxide
! rowspan="2" | Carbon number !! colspan="2" | δ /ppm || rowspan="2" | Δδ /ppm (Model values - Lit. values)
|-
! Molecular model !! Literature [Ref]
|-
| 25 || 22.59 || 19.83 !!
|-
| 5 || 24.17 || 21.39
|-
| 15 || 24.57 || 22.21
|-
| 24 || 26.51 || 25.35
|-
| 16 || 28.42 || 25.56
|-
| 11 || 32.58 || 30.00
|-
| 22 || 33.72 || 35.47
|-
| 13 || 38.73 || 36.78
|-
| 6 || 41.35 || 38.73
|-
| 8 || 44.16 || 40.82
|-
| 9 || 45.80 || 43.28
|-
| 4 || 48.11 || 45.53
|-
| 19 || 49.67 || 50.94
|-
| 14,1 || 55.03 || 51.30
|-
| 2 || 65.94 || 60.53
|-
| 3 || 93.27 || 74.61
|-
| 18 || 120.22 || 120.90
|-
| 17 || 148.01 || 148.72
|-
| 12 || 213.05 || 211.49
|}

http://pubs.rsc.org/en/content/articlepdf/2009/ob/b900719a {{DOI| 10.1039/B900719A}}

1
H
NMR (400 MHz; CDCl3) d = 7.44 (1H, d, J = 7 Hz), 7.33–7.21
(2H, m), 7.13 (1H, d, J =7 Hz), 3.89 (1H, d, J =4 Hz), 3.77 (1H,
t, J =4 Hz), 2.83–2.79 (1H, m), 2.59–2.55 (1H, m), 2.49–2.41 (1H,
m), 1.80–1.76 (1H, m);

13C NMR (100 MHz; CDCl3) d = 137.1,
132.9, 129.9, 129.8, 128.8, 126.5, 55.5, 53.2, 24.8 and 22.2;

===Assigning the absolute configuration of two epoxides===

Assignment of the absolute configuration of the styrene epoxide and 1,2-dihydronapthalene oxide can be achieved in three different ways:

* investigation of literature

* calculation of chiroptical properties including

:a) Optical Rotatory Dispersion, ORD

:b) Electronic Circular Dichroism, ERD

:c) Vibrational Circular Dichroism, VCD

* calculation of properties of the transition state for the reaction

====Reported literature====

====Chiroptical properties of the product epoxides====

Your task in the computational part of the experiment is to calculate what the expected chiroptical properties of this epoxide should be for a specified enantiomer and by comparing this with the value you will have measured in the experimental part to predict what the enantioselectivity of this catalyst is. Three chiroptical properties can be useful in this regard:

The optical rotation at a specified wavelength of light (the optical rotatory power, or ORP) or the values for a range of wavelengths (the Optical rotatory dispersion, or ORD).
The electronic circular dichroism (ECD)
The vibrational circular dichroism (VCD).

All these can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the 3rd year laboratory. The ECD, which in effect is the UV/Vis spectrum recorded with polarised light, is actually useless for the epoxides because no appropriate chromophore exists for the epoxides. VCD is an excellent technique[6] but the appropriate instrument is not available in the department.
To find the computed value, you cannot use Avogadro or Gaussview, but you have to inspect the .log file instead, where it appears as e.g. [ALPHA] ( 5890.0 A) = -324.5 deg. This gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 30 non-hydrogen atoms should not be attempted.

'''Styrene epoxide'''

ORD {{DOI|10042/26689}}:
[Alpha] ( 5890.0 A) = -30.40 deg °

optical rotation 589 nm 25 °C -33.3 deg http://pubs.acs.org/doi/abs/10.1021/ja00853a029 Frederick R. Jensen , Ronald C. KiskisJ. Am. Chem. Soc., 1975, 97 (20), pp 5825–5831DOI: 10.1021/ja00853a029

ECD {{DOI|10042/26687}}:
As styrene epoxide does not have a choromophore that can absorb wavelengths in UV-Vis region, this data is invalid. However, the spectrum was still produced [[Media:Yi11styreneepoxide optimised ECD 1 spectrum.PNG|here]].

VCD {{DOI|10042/26685}}:
[[File:Yi11styreneepoxide optimised VCD 1 spectrum.PNG|300px]]

'''1,2-dihydronapthalene oxide'''

ORD {{DOI|10042/26688}}
[Alpha] ( 5890.0 A) = 35.86 deg °

ECD {{DOI|10042/26686}}
As above, the spectrum was can be found [[Media:Yi11DHNO optimised ECD 1 spectrum.PNG|here]].

VCD: {{DOI|10042/26672}}
[[File:Yi11DHNO optimised VCD 1 spectrum.PNG|300px]]

====Transition state properties of epoxidation====

Only used Jacobsen catalyst - no TS available for dihydronapthalene oxide so investigate cis-β-methyl styrene instead.

Using the (calculated) properties of transition state for the reaction {{DOI|10.6084/m9.figshare.860446}}{{DOI|10.6084/m9.figshare.860449}}

'''Styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R-styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R !! S
|-
| G /Hartree/particle || (R1-3343.960889) R2 -3343.962162 || S1 -3343.969197 (S2 -3343.963191)
|-
| G /kJmol-1 || -8779572.656 || -8779591.127
|-
| ΔG /kJmol-1 R-S || colspan="2" | 18.471
|-
| K || colspan="2" | 1728.973
|-
| ee /% || 99.94 || Lit. 99<ref name="ee styepox">S. E. Schaus , B.t D. Brandes , J. F. Larrow, M. Tokunaga , K. B. Hansen , A. E. Gould , M. E. Furrow , and E. N. Jacobsen *, ''J. Am. Chem. Soc.'', '''2002''', ''124(7)'', 1307-1315.{{DOI|10.1021/ja016737l}}</ref>
|}

ee 99 http://pubs.acs.org/doi/pdf/10.1021/ja016737l

'''cis-β-methyl styrene epoxide'''

{| class="wikitable" border="1"
|+ Calculation of enantiomeric excess of R,S-cis-β-methyl styrene epoxide
! rowspan="2" | Energy !! colspan="2" |Diastereoisomer
|-
! R,S !! S,R
|-
| G /Hartree/particle || RS1-3383.251060 (R2 -3383.250270) || SR1 -3383.259559 (S2 -3383.253442)
|-
| G /kJmol-1 || -8882725.658 || -8882747.972
|-
| ΔG /kJmol-1 R-S || colspan="2" | 22.314
|-
| K || colspan="2" | 8155.095287
|-
| ee /% || 99.98 || Lit. 82<ref name="ee styepox">W. Zhang and E. N. Jacobsen, ''J. Org. Chem.'', '''1991''', ''56(7)'', 2296-2298.{{DOI|10.1021/jo00007a012}}</ref>
|}

ee 82% R,S http://chem.wisc.edu/deptfiles/genchem/Chm346/pdf/48.pdf

R-S give ee of R
K= e^(G/-RT)
G=-RTlnK
ee = K/(1+K)*100

The relative computed free energy of the transition state can be used as a check for the enantiomeric assignment obtained by comparing computed and calculated optical rotations of the epoxide.
acquire the job output (as a .log file) from the data repository entries listed below,
identify the total energy for each system as corrected for entropy and zero-point thermal energies and including a solvation correction for water as solvent
discuss whether this theoretical prediction matches what has been reported for this reaction in the literature (and whether it matches your observations if you used this alkene in your experiments. These geometric models could of course be used as the starting template for editing to correspond to other alkenes). Your discussion could include:

Indicating the free energy difference between two diastereomeric transition states
Convert this to K, the ratio of concentrations of the two species based on this energy difference
Use K to work out the predicted enantiomeric excess of one epoxide over the other.

Jacobsen catalyst

For a fixed chirality for the Mn-based catalyst, two transition states can be envisaged for oxygen transfer from the Mn=O oxygen to phenylprop-1-ene; whether the (R,S)-epoxide or the (S,R) epoxide is formed (there are other possibilities, such as a transition state via a metalla-oxacyclobutane, but we will ignore these here). The transition states each have 90 atoms, and although they can be computed at a reasonably high level, each calculation takes about 96 hours to complete, which is impractical for this course. So it has been pre-computed for you to analyse. There are four possibilities, depending on whether the S,R or the R,S enantiomer is formed, and the endo/exo arrangement of the substrate in relation to the catalyst.

===Non-covalent interactions (NCI) in the active-site of the reaction transition state===

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Non-covalent interactions (NCI) include hydrogen bonds, electrostatic attractions and dispersion-like close approaches of pairs of atoms. As for normal covalent bonds, such NCI interactions can be defined by the properties of the electron density (and its curvatures)[7]An example of an NCI analysis is shown on the right, where the colours indicate whether the interaction is attractive (colour means blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). Arrow 1 points to the bond forming in a transition state (which can be considered half-covalent) and this type of NCI interaction is normally ignored entirely. Arrow 2 points to a real NCI interaction between e.g. the reacting substrate and the catalyst. Being green in this case means it is mildly attractive. Such diagrams help to identify (in a semi-qualitative manner) those regions of a reacting system where substrate and catalyst may be interacting, and hence may provide some clues as to the origins of stereoselectivity between the two.

Your task is to download one of the transition states listed in the tables above, compute the electron density for the system and subject it to an NCI analysis.

===Electronic topology (QTAIM) in the active-site of the reaction transition state===

Avogadro2 onto the Windows systems for this expt

[[File:Yi11styrene RR Jacobsen TS QTAIM.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick.PNG|200px]]

[[File:Yi11styrene RR Jacobsen TS QTAIM side.PNG|200px]] [[File:Yi11styrene RR Jacobsen TS QTAIM ballstick side.PNG|200px]]

This is complementary to the NCI (non-covalent) analysis, since it has the focus on the electron density (and its curvature) in the COVALENT regions of molecules (i.e. much '''stronger interactions''' we grace with the term bond) as well as the weaker interactions identified in a NCI analysis.

Arrow 2 in the diagram to the right for example identifies a topological point known as a BCP (bond critical point, defined by a region where the first derivative of the electron density with respect to each of the three coordinates of that point is zero) which has a curvature (defined mathematically by the Hessian of the density ρ(r)) appropriate for a bond (C-O in this instance).
There are three other types of critical point:
those associated with nuclei (na),
those associated with rings (rcp) and
those associated with cages (ccl), but we are not concerned with those here.

Arrow 1 points to a weak non-covalent BCP (associated with weak interaction between oxygen and hydrogen).

Your task is to download one of the transition states listed in the tables above and subject it to a QTAIM analysis.

Identify any interesting BCPs, and

discuss whether they are associated with a covalent bond or not.

Note the position of the BCP (approximately) relative to the two atoms it may connect.

==Conclusion==

==References==

<references />