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Rep:Mod:melody

Rep:Mod:melody

2014-03-21T15:21:05Z

Ptf11: /* References */

=Introduction=
=Conformational analysis using Molecular Mechanics=
==The Hydrogenation of Cyclopentadiene Dimer==
===Cyclopentadiene Dimers===
Cyclopentadiene dimerises to produce specifically the endo dimer rather than the exo dimer. Using Avogadro, the two products were defined and their geometries optimised using the MMFF94(s) force field option.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcycloendo.jpg|110px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloendo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcycloexo.jpg|130px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloexo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.29872
| style="text-align: right;"|3.38094
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.42064
| style="text-align: right;"|29.06625
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-1.93752
| style="text-align: right;"|-1.89925
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.02382
| style="text-align: right;"|0.01615
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46181
| style="text-align: right;"|-1.12786
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|12.20843
| style="text-align: right;"|12.63198
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|14.05004
| style="text-align: right;"|12.90736
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|57.60233
! style="text-align: right;"|54.97559
|}
||

[[File:Ptfcyclorxnscheme.jpg|650px|thumb|Reaction mechanism for dimerisation of cyclopentadiene]]
|-
|
Although the endo product is higher in energy than the exo product by 2.63 kcal/mol, the less thermodynamically stable endo product is formed as there is stabilizing secondary orbital interaction (of the pi orbitals) in the transition state of the endo product, whereas there is no such interaction in the transition state of the exo product. The dimerisation of cyclopentadiene is thus kinetically controlled, and the endo product the kinetic product.

The energy difference between endo and exo products is largely due to the increase in the angle bending energy, with a difference of 2.35 kcal mol-1. The angle bending energy is defined as the energy involved to bend a bond away from its equilibrium angle. In the endo conformation, the ring, which is formed by joining two adjacent axial position (concave arrangement for the two rings), tends to bend upwards to the equatorial position to minimize steric hindrance with the other ring and hence causes an increase in angle bending energy. In the exo product, the ring is joined at the equatorial position (linear arrangement for the two rings) and avoids steric hindrance with the other ring, hence there is less increase in angle bending energy.
|}

===Hydrogenation===
Hydrogenation of the endo dimer proceeds to give initially one of the dihydro derivatives 3 or 4. Only after prolonged hydrogenation is the tetrahydro derivative formed.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo3.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo3.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo4.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo4.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.31116
| style="text-align: right;"|2.82326
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.93515
| style="text-align: right;"|24.68525
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-2.10212
| style="text-align: right;"|-1.65728
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.01317
| style="text-align: right;"|0.00027
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46918
| style="text-align: right;"|-0.37919
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|13.63801
| style="text-align: right;"|10.63816
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|5.11952
| style="text-align: right;"|5.14701
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|50.44571
! style="text-align: right;"|41.25748
|}
||

[[File:Ptfcyclohydrogenation.jpg|350px|thumb|Hydrogenation of cyclopentadiene endo dimer]]
|-
|
Product 4 is lower in energy than product 3 by 9.19 kcal mol-1. The difference in energy is again largely due to the angle bending energy difference of 7.25 kcal mol-1, and to a smaller extent, the Van Der Waals energy difference of 3.00 kcal mol-1 due to the greater steric repulsion in 3. The large difference in the angle bending energy is due to the geometry of the 4 sp2 carbons in the endo product of the dimer. sp2 carbons in a ring equal or smaller than 6-membered ring is generally unstable as the 120° angle favoured by sp2 centres cannot be geometrically achieved without ring strain. The double bond at the norbornene part of the molecule has sp2 carbons shared by both a 5-membered and a 6-membered ring whereas the sp2 carbons at the other end only causes ring strain to one 5-membered ring. Hence, product 4 would have more bond angles that are closer to equilibrium and hence, possesses lower ring strain and a lower angle bending energy. Product 4 should be formed as the thermodynamic product, as confirmed in literature.<ref>D. Skala and J. Hanika, "Kinetics of Dicyclopentadiene Hydrogenation Using Pd/C Catalyst", ''Pet. Coal'', '''2003''', 45, 105-108.</ref> The hydrogenation of endo dicyclopentadiene is thus thermodynamically controlled, and the the first hydrogenation occurs at the norbornene part of the molecule.
|}

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
In the total synthesis of Taxol (an important drug in the treatment of ovarian cancers), a key intermediate 9 or 10is initially synthesised with the carbonyl group pointing either up or down. By using the MMFF94(s) force field option in Avagadro, the relative stabilities of these two atropisomers were explored. After experimenting with the different conformations of intermediate 9 and 10, it was found that a "chair" conformation of both compounds 9 and 10, as shown in the table below, resulted in optimised structures with the lowest energies. The energies of the chair conformations of intermediates 9 and 10 are compared below.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo9.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo9.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo10.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo10.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|7.65248
| style="text-align: right;"|7.56126
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|28.27472
| style="text-align: right;"|18.82557
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
| style="text-align: right;"|-0.13605
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.97217
| style="text-align: right;"|0.83644
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.31893
| style="text-align: right;"|0.19401
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|33.10145
| style="text-align: right;"|33.32591
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|0.30721
| style="text-align: right;"|-0.05433
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|70.54748
! style="text-align: right;"|60.55280
|}
||

Atropisomer 10 is lower in energy, with a difference of 9.99 kcal/mol, and therefore is more thermodynamically stable than atopisomer 9. The difference in energy is largely due to the angle bending energy (9.45 kcal/mol) which makes up the majority of the total energy difference. This indicates that the bond angle of the carbonyl group in atropisomer 10 is much closer to the equilibrium angle than atopisomer 9.

This can be proven by inquiring the bond angles of the bonds involving sp2 and sp3 hybridised carbon atoms in the carbonyl group in Atropisomer 9 and 10 in Gaussview, which is summarised below.

{| class="wikitable"
! Atropisomer !! Bond Type !! Carbonyl Group Bond Angles (°) || Equilibrium Angle (°)
|-
| rowspan="2" | [[File:Ptfcyclo9.jpg|120px]] || Bonds involing sp2 hybridised carbons || 117-123 || 120
|-
| Bonds involing sp3 hybridised carbons || 100-108 || 109.5
|-
| rowspan="2" | [[File:Ptfcyclo10.jpg|120px]] || Bonds involing sp2 hybridised carbons || 120-121 || 120
|-
| Bonds involing sp3 hybridised carbons || 105-109 || 109.5
|}

Maier and Schleyer<ref name="hyper stable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. {{DOI|10.1021/ja00398a003}}</ref> concluded that double bond joined to a bridge is particularly stable due to its cage structure, thus, its corresponding hydrogenated product will experience more strain, which explains why bridgehead alkenes react slowly.

Other conformers for these atropisomers include a boat structure, which is less stable than the corresponding chair conformation. The increase in energy is due to an increase in angle bending torsional energy as the cyclohexane ring experiences greater torsional strain in the eclipsed boat conformation.
|}

=Spectroscopic Simulation using Quantum Mechanics=
==Optimization of Molecule 18==
[[File:Ptf18.jpg|thumb|Molecule 18|150px]]
{| class="wikitable" style="float: left;"
! colspan="12" align="center"|Molecule 18 Optimization
|-
| rowspan="12" align="center"|
[[File:Ptf18.jpg|150px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
! Energy
! kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|14.99958
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|30.80948
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.62729
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.89658
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|49.39433
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|-6.05522
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|100.44220
|}

The molecule 18 is a derivative of molecule 10, for which spectroscopic information has been reported.<ref name="spectra">Spectroscopic data: 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> The objective here is to simulate the 1H and 13C spectra and compare them with the literature values to see if the latter has been correctly interpreted and assigned.

Using the Avogadro or ChemBio3D program, and using the MMFF94s mechanics force field, the starting molecules 18 was optimized to an energy minimum. Based on the previous calculations involving the cyclopentadiene dimer and the Taxol intermediate atropisomer, it was predicted that the lowest energy conformation of compound 18 would be an endo (at the large ring), chair (at the smaller cyclohexane ring) conformer, as illustrated in the jmol file on the left. This structure is also supported by crystallographic data from literature.<ref name="spectra"/>

==Spectroscopic Simulation of Molecule 18==
By using Avogadro's Gaussian Geometry optimization and illustrating using GaussView, the following NMR data was obtained. The .log file of the simulation can be found [[Media:Ptf18.log|here]], and the digital repository here {{DOI|10042/28194}}.

{| class="wikitable"
!
Atom Numbering
|
[[File:Ptf18label.jpg|550px]]
| align="center" |
[[File:Ptf18simple.jpg|400px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! 1H NMR
||
[[File:Ptf18hnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
5.9943373355 1.0000 10
3.1383405979 2.0000 52,50
2.9976414945 1.0000 53
2.9268494729 2.0000 51,36
2.8117162381 2.0000 34,35
2.6103072452 1.0000 24
2.5535190605 1.0000 16
2.4785547510 1.0000 23
2.3355375185 2.0000 39,43
2.2759636135 1.0000 37
1.9983425520 2.0000 25,26
1.8486946118 2.0000 38,22
1.6500945214 1.0000 30
1.5815091205 1.0000 33
1.5179130786 2.0000 27,41
1.3617269195 1.0000 40
1.3035148468 1.0000 44
1.2231834398 2.0000 42,31
0.9508535600 3.0000 32,29,28
0.6216079526 1.0000 45
</pre>
|-
! 13C NMR
||
[[File:Ptf18cnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
213.0961325830 1.0000 11
148.0547320284 1.0000 4
120.2667148682 1.0000 9
93.3213936895 1.0000 17
65.9859553102 1.0000 13
55.0715405775 2.0000 3,12
49.7214718290 1.0000 5
48.1628662916 1.0000 18
45.8501042512 1.0000 49
44.1990174424 1.0000 48
41.3930608867 1.0000 20
38.7739494869 1.0000 8
33.7645805938 1.0000 15
32.6242885826 1.0000 14
28.4566038455 1.0000 2
26.5581305940 1.0000 6
24.6172011030 1.0000 1
24.2187982580 1.0000 19
22.6332903141 1.0000 7
</pre>
|}

The obtained spectroscopic data was then compared with literature values<ref name="spectra"/> shown below.

{| class="wikitable"
! colspan="2" | Literature Values
|-
| colspan="2" align="center" | [[File:Ptf18lit.jpg]]
|-
! 1H NMR Comparison !! 13C NMR Comparison
|-
| align="center" |[[File:Ptfhnmrcomp.jpg]]

|align="center" |
[[File:Ptfcnmrcomp.jpg]]

|-
|
[[File:Ptfhnmrcompic.jpg]]
||
[[File:Ptfcnmrcompic.jpg]]
|}

=Analysis of the Properties of Synthesised Alkene Epoxides=
==Structure of Catalsysts==
===Structure 21===
{| align="center"
| [[File:Ptf21struc.jpg|300p]] || [[File:Ptf21.jpg|500px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 21 was visualized on the Mercury program.

It was found that the six membered heteroatomic ring of structure 21 adopted a chair conformation, which was expected, to minimize torsional strain, with the Oxygen atom (O2 - with superscript 2 indicating that the atom is numbered 2) as the non-planar end. It was also discovered that substituent oxygen atoms such as O2 were in an axial position rather than the more sterically unhindered equatorial position. This allows an anti-periplanar alignment between the oxygen lone pair, which is a good donor, and the adjacent C-O2 σ* orbital which is a good acceptor, leading to a stabilising interaction. Consequently, O6 will lose electron density and the C-O2 bond lengthened as electrons are interacting with its anti-bonding orbital. The anomeric effectalso occurs in five-membered rings, but to a lesser extent due to deviations from an anti-periplanar alignment.

There are three anomeric centres present in the molecule 21, which are at C2, C9 and C10. At C2, the C2-O2 (1.423Å) bond is longer than at C2-O6 (1.415Å). At C9 and C10, C9-O2(1.454Å) and C10-O4 (1.456Å) are both longer than adjacent C9-O1(1.423Å) and C10-O5 (1.428Å) bonds. Interestingly, even though O1 and O2 appear symmetrical around C9, and similiarly for O4 and O5 around C10, only one oxygen's lone pair (O1 for C9, O5 for C10) can align in an anti-periplanar fashion to the σ* orbital of the adjacent C-O bonds. Otherwise, the mutual anomeric effects would cause each adjacent C-O bonds to be equaivalent in length.

===Structure 23===
{| align="center"
| [[File:Ptf23struc.jpg|150px]] || [[File:Ptf23.jpg|600px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 23 was visualized on the Mercury program.

Molecule 23 has a 5-coordinated manganese centre with a square pyramidal structure where 4 atoms joined by ring-like structures and bridges are coordinated to the metal center in an approximate plane, with a perpendicular chlorine atom coordinated to the metal center. This approximate planar nature is due to the delocalisation of electron densities at the salen ligands at either sides. The cyclohexane ring adopts a low energy chair conformation and has two chiral C atoms attached to N, thus defining the stereochemistry of the Jacobsen catalyst to be either (R,R) or (S,S).

The bulky tBu groups on the Salen ligands prevent a side-on approach of the alkenes due to steric hindrance, ensuring epoxidation enantioselectivity. Without the tBu groups, alkenes could have side-on approach to the catalyst, as shown when the tBu groups were replaced with methyl gourps. <ref name="10.1021/ja00018a068>E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng, ''J. Am. Chem. Soc.'', '''1991''', ''113'', 7063–7064; {{DOI|10.1021/ja00018a068}}</ref>. As seen above, the two central tBu groups are in close proximity, and the interaction between the hydrogen atoms (represented by the green lines) is an attractive interaction. The maximum attraction for non-bonded hydrogens are at 2.4Å, while repulsion only occurs when the atoms are less than 2.1Å apart from each other.<ref>M. Mantina, A. C. Chamberlin, R. Valero, C. J. Cramer, and D. G. Truhlar, "Consistent van der Waals Radii for the Whole Main Group", ''J. Phys. Chem. A'', '''2009''', 113, 5806–5812.{{DOI|10.1021/jp8111556}}</ref> This attractive interaction, coupled with the steric effects of the outer tBu groups, results in increased catalyst thermodynamic stability and selectivity.

==Simulated NMR properties of Epoxides==
===Styrene Oxide===
{| class="wikitable"
! Enantiomer !! R-Styrene oxide !! S-Styrene oxide
|-
! Labelled Structures || [[File:Ptfrsty.jpg|300px]] || [[File:Ptfssty.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrstry.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssty.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfrstry.log|.log File]]
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfssty.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfsstyhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfsstycnmr.svg|490px]]
|}

===Dihydronaphthalene Oxide===
{| class="wikitable"
! Enantiomer !! (S,R)-dihydronaphthalene oxide !! (R,S)-dihydronaphthalene oxide
|-
! Labelled Structures || [[File:Ptfsrnaph.jpg|300px]] || [[File:Ptfrsnaph.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfsrnaph.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrsnaph.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28211}} & [[Media:Ptfsrnaph.log|.log File]]
| align="center" | {{DOI|10042/28210}} & [[Media:Ptfrsnaph.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfrsnaphhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfrsnaphcnmr.svg|490px]]
|}

==Assigning the absolute configuration of the product==
===Simulated chiroptical properties===
Computational methods can be used to calculate the expected chiroptical properties of epoxides for a specified enantiomer, which can be comparing with experimental and literature values to predict the enantioselectivity of the catalyst. 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 properties can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the Imperial College 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, but the appropriate instrument is not available in the department. Thus, due to these limitations, only the optical rotation was simulated, with the following results.

{| class="wikitable"
! Epoxide !! R-Styrene oxide !! S-Styrene oxide !! (S,R)-dinaphthalene oxide !! (R,S)-dinaphthalene oxide
|-
! Simulated Optical Rotation (CHCl3, 589nm, 25°C)
| align="center" | -30.14°
| align="center" | +30.41°
| align="center" | +155.81°
| align="center" | -155.82°
|-
! Literature Optical Rotation ((CHCl3, 589nm)
| align="center" | -23.7°, 31°C<ref>E.N. Jacobsen, D.E. White, "New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions",'' Tetrahedron Asymmetry'', '''2003''', 14, 3633-3638. {{DOI|10.1016/j.tetasy.2003.09.024}}</ref>
| align="center" | +32.1°, 25°C<ref>H. Lin, J. Qiao, Y. Liu, and Z.-L. Wu, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B Enzym.'', '''2010''', 67, 236–241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref>
| align="center" | +133°<ref>D.R. Boyd, N.D. Sharma, R. Agarwal, N.A. Kerley, R.A.S. mCmORDIE, A. Smith, H. Dalton, A.J. Blacker and G.N. Sheldrake "A new synthetic route to non-K and bay region arene oxide metabolites from cis-diols", ''J. Chem. Soc., Chem. Commun.'', '''1994''', 14, 1693-1694. {{DOI|10.1039/C39940001693}}</ref>
| align="center" | -144.9°, 25°C<ref>H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki, "Rational design of Mn-salen catalyst (2): Highly enantioselective epoxidation of conjugated cis olefins", ''Tetrahedron'', '''1994''', 50, 11827-11838. {{DOI|10.1016/S0040-4020(01)89298-X}}</ref>
|-
! Digital Repository
| align="center" | {{DOI|10042/28214}}
| align="center" | {{DOI|10042/28244}}
| align="center" | {{DOI|10042/28243}}
| align="center" | {{DOI|10042/28242}}
|}

It was observed that literature values are lower than the simulated values in magnitude. This is most likely due to a less than 100% enantiomeric purity. The simulation does not take this into consideration, thus, during simulation, a 100% enantiomeric purity was assumed. Temperature could also have been a factor in the difference in optical rotation, but this effect of this difference is difficult to predict. However, the simulated and literature values seem to to be satisfactorily in agreement.

===Calculated properties of transition state for the reaction===
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. This is calculated via the Curtin-Hammett Principle, which relates the relative concentration of two products to the difference in energy of the transition states for two different conformers of a molecule. <ref>J. I. Seeman, "The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts", ''J. Chem. Educ.'',''' 1986''', 63, 42–48. {{DOI|10.1021/ed063p42}}</ref>

The principle can be simplified to the following equations;

'''K=''e''-(ΔG°TS/RT)''', where '''K=[A]/[B]''', the ratio of concentration between two conformers, and [A] and [B] are the concentrations of conformer A and B respectively, and ΔG°TS is the relative computed free energy of the transition state, i.e, the difference between the energy levels of the transition states for each enantiomer.

The Enantiomeric Excess '''(EE)''' is defined as '''([A]-[B])/([A]+[B]) * 100%.'''

Since K=[A]/[B], [A]=K[B], and thus, '''EE= (K[B]-[B])/K[B]+[B]) * 100%.'''

Therefore, '''EE = (K-1)/(K+1) * 100%'''

A list of possible transition states for trans-β methyl styrene using the Shi and Jacobsen's catalyst is available in digital repositories. By calculating the energy difference between the lowest energy transition state (which represents the most probably pathway for each catalytic epoxidation), ΔG°TS/RT can be calculated.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Shi Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (1)
|| -1343.032443 Ha
|-
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (2)
|| -1343.024742 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.007701 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.021897257 x 104 J/mol
|-
| K
|| 3499.272792
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfrrmethshi.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrrmethshi.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Jacobsen Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (1)
|| -3383.262481 Ha
|-
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (2)
|| -3383.254344 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.008137 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.13637x 104 J/mol
|-
| K
|| 5554.228363
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfssmethjac.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssmethjac.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

==Non-covalent Interactions in the Active-site of the Reaction Transition State==
{|
|
<jmol>
<jmolApplet>
<title>Orbital</title><color>black</color><size>300</size>
<script>isosurface color orange purple "images/5/5f/Ptf.cub.jvxl" translucent;</script>
<uploadedFileContents>ptf.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.

The NCI shown on the left was generated with the lowest energy transition state of a Jacobsen epoxidation on S,S-trans-β methyl styrene. The colours indicate whether the interaction is attractive (blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). It was observed that the alkene is aligned endo to the catalyst, allowing an attractive interaction between the phenyl group of the methyl styrene and the phenyl group of the Salen ligands, lowers the transition state energy and thus improving enantiomeric selectivity. Additionally, the two phenyl groups are also in a staggered conformation, thus minimizing steric strain. The attraction between the tBu groups also supports the hypothesis that the internuclear distance between the tBu H atoms promoted an attractive interaction.
|}

== Electronic Topology (QTAIM) in the Active-site of the Reaction Transition State==

==Possible Alkenes for Further Investigation==

=References=
<references />

Rep:Mod:melody

2014-03-21T15:13:53Z

Ptf11: /* References */

=Introduction=
=Conformational analysis using Molecular Mechanics=
==The Hydrogenation of Cyclopentadiene Dimer==
===Cyclopentadiene Dimers===
Cyclopentadiene dimerises to produce specifically the endo dimer rather than the exo dimer. Using Avogadro, the two products were defined and their geometries optimised using the MMFF94(s) force field option.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcycloendo.jpg|110px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloendo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcycloexo.jpg|130px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloexo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.29872
| style="text-align: right;"|3.38094
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.42064
| style="text-align: right;"|29.06625
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-1.93752
| style="text-align: right;"|-1.89925
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.02382
| style="text-align: right;"|0.01615
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46181
| style="text-align: right;"|-1.12786
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|12.20843
| style="text-align: right;"|12.63198
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|14.05004
| style="text-align: right;"|12.90736
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|57.60233
! style="text-align: right;"|54.97559
|}
||

[[File:Ptfcyclorxnscheme.jpg|650px|thumb|Reaction mechanism for dimerisation of cyclopentadiene]]
|-
|
Although the endo product is higher in energy than the exo product by 2.63 kcal/mol, the less thermodynamically stable endo product is formed as there is stabilizing secondary orbital interaction (of the pi orbitals) in the transition state of the endo product, whereas there is no such interaction in the transition state of the exo product. The dimerisation of cyclopentadiene is thus kinetically controlled, and the endo product the kinetic product.

The energy difference between endo and exo products is largely due to the increase in the angle bending energy, with a difference of 2.35 kcal mol-1. The angle bending energy is defined as the energy involved to bend a bond away from its equilibrium angle. In the endo conformation, the ring, which is formed by joining two adjacent axial position (concave arrangement for the two rings), tends to bend upwards to the equatorial position to minimize steric hindrance with the other ring and hence causes an increase in angle bending energy. In the exo product, the ring is joined at the equatorial position (linear arrangement for the two rings) and avoids steric hindrance with the other ring, hence there is less increase in angle bending energy.
|}

===Hydrogenation===
Hydrogenation of the endo dimer proceeds to give initially one of the dihydro derivatives 3 or 4. Only after prolonged hydrogenation is the tetrahydro derivative formed.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo3.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo3.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo4.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo4.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.31116
| style="text-align: right;"|2.82326
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.93515
| style="text-align: right;"|24.68525
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-2.10212
| style="text-align: right;"|-1.65728
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.01317
| style="text-align: right;"|0.00027
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46918
| style="text-align: right;"|-0.37919
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|13.63801
| style="text-align: right;"|10.63816
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|5.11952
| style="text-align: right;"|5.14701
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|50.44571
! style="text-align: right;"|41.25748
|}
||

[[File:Ptfcyclohydrogenation.jpg|350px|thumb|Hydrogenation of cyclopentadiene endo dimer]]
|-
|
Product 4 is lower in energy than product 3 by 9.19 kcal mol-1. The difference in energy is again largely due to the angle bending energy difference of 7.25 kcal mol-1, and to a smaller extent, the Van Der Waals energy difference of 3.00 kcal mol-1 due to the greater steric repulsion in 3. The large difference in the angle bending energy is due to the geometry of the 4 sp2 carbons in the endo product of the dimer. sp2 carbons in a ring equal or smaller than 6-membered ring is generally unstable as the 120° angle favoured by sp2 centres cannot be geometrically achieved without ring strain. The double bond at the norbornene part of the molecule has sp2 carbons shared by both a 5-membered and a 6-membered ring whereas the sp2 carbons at the other end only causes ring strain to one 5-membered ring. Hence, product 4 would have more bond angles that are closer to equilibrium and hence, possesses lower ring strain and a lower angle bending energy. Product 4 should be formed as the thermodynamic product, as confirmed in literature.<ref>D. Skala and J. Hanika, "Kinetics of Dicyclopentadiene Hydrogenation Using Pd/C Catalyst", ''Pet. Coal'', '''2003''', 45, 105-108.</ref> The hydrogenation of endo dicyclopentadiene is thus thermodynamically controlled, and the the first hydrogenation occurs at the norbornene part of the molecule.
|}

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
In the total synthesis of Taxol (an important drug in the treatment of ovarian cancers), a key intermediate 9 or 10is initially synthesised with the carbonyl group pointing either up or down. By using the MMFF94(s) force field option in Avagadro, the relative stabilities of these two atropisomers were explored. After experimenting with the different conformations of intermediate 9 and 10, it was found that a "chair" conformation of both compounds 9 and 10, as shown in the table below, resulted in optimised structures with the lowest energies. The energies of the chair conformations of intermediates 9 and 10 are compared below.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo9.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo9.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo10.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo10.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|7.65248
| style="text-align: right;"|7.56126
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|28.27472
| style="text-align: right;"|18.82557
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
| style="text-align: right;"|-0.13605
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.97217
| style="text-align: right;"|0.83644
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.31893
| style="text-align: right;"|0.19401
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|33.10145
| style="text-align: right;"|33.32591
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|0.30721
| style="text-align: right;"|-0.05433
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|70.54748
! style="text-align: right;"|60.55280
|}
||

Atropisomer 10 is lower in energy, with a difference of 9.99 kcal/mol, and therefore is more thermodynamically stable than atopisomer 9. The difference in energy is largely due to the angle bending energy (9.45 kcal/mol) which makes up the majority of the total energy difference. This indicates that the bond angle of the carbonyl group in atropisomer 10 is much closer to the equilibrium angle than atopisomer 9.

This can be proven by inquiring the bond angles of the bonds involving sp2 and sp3 hybridised carbon atoms in the carbonyl group in Atropisomer 9 and 10 in Gaussview, which is summarised below.

{| class="wikitable"
! Atropisomer !! Bond Type !! Carbonyl Group Bond Angles (°) || Equilibrium Angle (°)
|-
| rowspan="2" | [[File:Ptfcyclo9.jpg|120px]] || Bonds involing sp2 hybridised carbons || 117-123 || 120
|-
| Bonds involing sp3 hybridised carbons || 100-108 || 109.5
|-
| rowspan="2" | [[File:Ptfcyclo10.jpg|120px]] || Bonds involing sp2 hybridised carbons || 120-121 || 120
|-
| Bonds involing sp3 hybridised carbons || 105-109 || 109.5
|}

Maier and Schleyer<ref name="hyper stable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. {{DOI|10.1021/ja00398a003}}</ref> concluded that double bond joined to a bridge is particularly stable due to its cage structure, thus, its corresponding hydrogenated product will experience more strain, which explains why bridgehead alkenes react slowly.

Other conformers for these atropisomers include a boat structure, which is less stable than the corresponding chair conformation. The increase in energy is due to an increase in angle bending torsional energy as the cyclohexane ring experiences greater torsional strain in the eclipsed boat conformation.
|}

=Spectroscopic Simulation using Quantum Mechanics=
==Optimization of Molecule 18==
[[File:Ptf18.jpg|thumb|Molecule 18|150px]]
{| class="wikitable" style="float: left;"
! colspan="12" align="center"|Molecule 18 Optimization
|-
| rowspan="12" align="center"|
[[File:Ptf18.jpg|150px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
! Energy
! kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|14.99958
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|30.80948
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.62729
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.89658
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|49.39433
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|-6.05522
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|100.44220
|}

The molecule 18 is a derivative of molecule 10, for which spectroscopic information has been reported.<ref name="spectra">Spectroscopic data: 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> The objective here is to simulate the 1H and 13C spectra and compare them with the literature values to see if the latter has been correctly interpreted and assigned.

Using the Avogadro or ChemBio3D program, and using the MMFF94s mechanics force field, the starting molecules 18 was optimized to an energy minimum. Based on the previous calculations involving the cyclopentadiene dimer and the Taxol intermediate atropisomer, it was predicted that the lowest energy conformation of compound 18 would be an endo (at the large ring), chair (at the smaller cyclohexane ring) conformer, as illustrated in the jmol file on the left. This structure is also supported by crystallographic data from literature.<ref name="spectra"/>

==Spectroscopic Simulation of Molecule 18==
By using Avogadro's Gaussian Geometry optimization and illustrating using GaussView, the following NMR data was obtained. The .log file of the simulation can be found [[Media:Ptf18.log|here]], and the digital repository here {{DOI|10042/28194}}.

{| class="wikitable"
!
Atom Numbering
|
[[File:Ptf18label.jpg|550px]]
| align="center" |
[[File:Ptf18simple.jpg|400px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! 1H NMR
||
[[File:Ptf18hnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
5.9943373355 1.0000 10
3.1383405979 2.0000 52,50
2.9976414945 1.0000 53
2.9268494729 2.0000 51,36
2.8117162381 2.0000 34,35
2.6103072452 1.0000 24
2.5535190605 1.0000 16
2.4785547510 1.0000 23
2.3355375185 2.0000 39,43
2.2759636135 1.0000 37
1.9983425520 2.0000 25,26
1.8486946118 2.0000 38,22
1.6500945214 1.0000 30
1.5815091205 1.0000 33
1.5179130786 2.0000 27,41
1.3617269195 1.0000 40
1.3035148468 1.0000 44
1.2231834398 2.0000 42,31
0.9508535600 3.0000 32,29,28
0.6216079526 1.0000 45
</pre>
|-
! 13C NMR
||
[[File:Ptf18cnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
213.0961325830 1.0000 11
148.0547320284 1.0000 4
120.2667148682 1.0000 9
93.3213936895 1.0000 17
65.9859553102 1.0000 13
55.0715405775 2.0000 3,12
49.7214718290 1.0000 5
48.1628662916 1.0000 18
45.8501042512 1.0000 49
44.1990174424 1.0000 48
41.3930608867 1.0000 20
38.7739494869 1.0000 8
33.7645805938 1.0000 15
32.6242885826 1.0000 14
28.4566038455 1.0000 2
26.5581305940 1.0000 6
24.6172011030 1.0000 1
24.2187982580 1.0000 19
22.6332903141 1.0000 7
</pre>
|}

The obtained spectroscopic data was then compared with literature values<ref name="spectra"/> shown below.

{| class="wikitable"
! colspan="2" | Literature Values
|-
| colspan="2" align="center" | [[File:Ptf18lit.jpg]]
|-
! 1H NMR Comparison !! 13C NMR Comparison
|-
| align="center" |[[File:Ptfhnmrcomp.jpg]]

|align="center" |
[[File:Ptfcnmrcomp.jpg]]

|-
|
[[File:Ptfhnmrcompic.jpg]]
||
[[File:Ptfcnmrcompic.jpg]]
|}

=Analysis of the Properties of Synthesised Alkene Epoxides=
==Structure of Catalsysts==
===Structure 21===
{| align="center"
| [[File:Ptf21struc.jpg|300p]] || [[File:Ptf21.jpg|500px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 21 was visualized on the Mercury program.

It was found that the six membered heteroatomic ring of structure 21 adopted a chair conformation, which was expected, to minimize torsional strain, with the Oxygen atom (O2 - with superscript 2 indicating that the atom is numbered 2) as the non-planar end. It was also discovered that substituent oxygen atoms such as O2 were in an axial position rather than the more sterically unhindered equatorial position. This allows an anti-periplanar alignment between the oxygen lone pair, which is a good donor, and the adjacent C-O2 σ* orbital which is a good acceptor, leading to a stabilising interaction. Consequently, O6 will lose electron density and the C-O2 bond lengthened as electrons are interacting with its anti-bonding orbital. The anomeric effectalso occurs in five-membered rings, but to a lesser extent due to deviations from an anti-periplanar alignment.

There are three anomeric centres present in the molecule 21, which are at C2, C9 and C10. At C2, the C2-O2 (1.423Å) bond is longer than at C2-O6 (1.415Å). At C9 and C10, C9-O2(1.454Å) and C10-O4 (1.456Å) are both longer than adjacent C9-O1(1.423Å) and C10-O5 (1.428Å) bonds. Interestingly, even though O1 and O2 appear symmetrical around C9, and similiarly for O4 and O5 around C10, only one oxygen's lone pair (O1 for C9, O5 for C10) can align in an anti-periplanar fashion to the σ* orbital of the adjacent C-O bonds. Otherwise, the mutual anomeric effects would cause each adjacent C-O bonds to be equaivalent in length.

===Structure 23===
{| align="center"
| [[File:Ptf23struc.jpg|150px]] || [[File:Ptf23.jpg|600px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 23 was visualized on the Mercury program.

Molecule 23 has a 5-coordinated manganese centre with a square pyramidal structure where 4 atoms joined by ring-like structures and bridges are coordinated to the metal center in an approximate plane, with a perpendicular chlorine atom coordinated to the metal center. This approximate planar nature is due to the delocalisation of electron densities at the salen ligands at either sides. The cyclohexane ring adopts a low energy chair conformation and has two chiral C atoms attached to N, thus defining the stereochemistry of the Jacobsen catalyst to be either (R,R) or (S,S).

The bulky tBu groups on the Salen ligands prevent a side-on approach of the alkenes due to steric hindrance, ensuring epoxidation enantioselectivity. Without the tBu groups, alkenes could have side-on approach to the catalyst, as shown when the tBu groups were replaced with methyl gourps. <ref name="10.1021/ja00018a068>E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng, ''J. Am. Chem. Soc.'', '''1991''', ''113'', 7063–7064; {{DOI|10.1021/ja00018a068}}</ref>. As seen above, the two central tBu groups are in close proximity, and the interaction between the hydrogen atoms (represented by the green lines) is an attractive interaction. The maximum attraction for non-bonded hydrogens are at 2.4Å, while repulsion only occurs when the atoms are less than 2.1Å apart from each other.<ref>M. Mantina, A. C. Chamberlin, R. Valero, C. J. Cramer, and D. G. Truhlar, "Consistent van der Waals Radii for the Whole Main Group", ''J. Phys. Chem. A'', '''2009''', 113, 5806–5812.{{DOI|10.1021/jp8111556}}</ref> This attractive interaction, coupled with the steric effects of the outer tBu groups, results in increased catalyst thermodynamic stability and selectivity.

==Simulated NMR properties of Epoxides==
===Styrene Oxide===
{| class="wikitable"
! Enantiomer !! R-Styrene oxide !! S-Styrene oxide
|-
! Labelled Structures || [[File:Ptfrsty.jpg|300px]] || [[File:Ptfssty.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrstry.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssty.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfrstry.log|.log File]]
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfssty.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfsstyhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfsstycnmr.svg|490px]]
|}

===Dihydronaphthalene Oxide===
{| class="wikitable"
! Enantiomer !! (S,R)-dihydronaphthalene oxide !! (R,S)-dihydronaphthalene oxide
|-
! Labelled Structures || [[File:Ptfsrnaph.jpg|300px]] || [[File:Ptfrsnaph.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfsrnaph.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrsnaph.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28211}} & [[Media:Ptfsrnaph.log|.log File]]
| align="center" | {{DOI|10042/28210}} & [[Media:Ptfrsnaph.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfrsnaphhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfrsnaphcnmr.svg|490px]]
|}

==Assigning the absolute configuration of the product==
===Simulated chiroptical properties===
Computational methods can be used to calculate the expected chiroptical properties of epoxides for a specified enantiomer, which can be comparing with experimental and literature values to predict the enantioselectivity of the catalyst. 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 properties can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the Imperial College 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, but the appropriate instrument is not available in the department. Thus, due to these limitations, only the optical rotation was simulated, with the following results.

{| class="wikitable"
! Epoxide !! R-Styrene oxide !! S-Styrene oxide !! (S,R)-dinaphthalene oxide !! (R,S)-dinaphthalene oxide
|-
! Simulated Optical Rotation (CHCl3, 589nm, 25°C)
| align="center" | -30.14°
| align="center" | +30.41°
| align="center" | +155.81°
| align="center" | -155.82°
|-
! Literature Optical Rotation ((CHCl3, 589nm)
| align="center" | -23.7°, 31°C<ref>E.N. Jacobsen, D.E. White, "New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions",'' Tetrahedron Asymmetry'', '''2003''', 14, 3633-3638. {{DOI|10.1016/j.tetasy.2003.09.024}}</ref>
| align="center" | +32.1°, 25°C<ref>H. Lin, J. Qiao, Y. Liu, and Z.-L. Wu, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B Enzym.'', '''2010''', 67, 236–241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref>
| align="center" | +133°<ref>D.R. Boyd, N.D. Sharma, R. Agarwal, N.A. Kerley, R.A.S. mCmORDIE, A. Smith, H. Dalton, A.J. Blacker and G.N. Sheldrake "A new synthetic route to non-K and bay region arene oxide metabolites from cis-diols", ''J. Chem. Soc., Chem. Commun.'', '''1994''', 14, 1693-1694. {{DOI|10.1039/C39940001693}}</ref>
| align="center" | -144.9°, 25°C<ref>H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki, "Rational design of Mn-salen catalyst (2): Highly enantioselective epoxidation of conjugated cis olefins", ''Tetrahedron'', '''1994''', 50, 11827-11838. {{DOI|10.1016/S0040-4020(01)89298-X}}</ref>
|-
! Digital Repository
| align="center" | {{DOI|10042/28214}}
| align="center" | {{DOI|10042/28244}}
| align="center" | {{DOI|10042/28243}}
| align="center" | {{DOI|10042/28242}}
|}

It was observed that literature values are lower than the simulated values in magnitude. This is most likely due to a less than 100% enantiomeric purity. The simulation does not take this into consideration, thus, during simulation, a 100% enantiomeric purity was assumed. Temperature could also have been a factor in the difference in optical rotation, but this effect of this difference is difficult to predict. However, the simulated and literature values seem to to be satisfactorily in agreement.

===Calculated properties of transition state for the reaction===
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. This is calculated via the Curtin-Hammett Principle, which relates the relative concentration of two products to the difference in energy of the transition states for two different conformers of a molecule. <ref>J. I. Seeman, "The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts", ''J. Chem. Educ.'',''' 1986''', 63, 42–48. {{DOI|10.1021/ed063p42}}</ref>

The principle can be simplified to the following equations;

'''K=''e''-(ΔG°TS/RT)''', where '''K=[A]/[B]''', the ratio of concentration between two conformers, and [A] and [B] are the concentrations of conformer A and B respectively, and ΔG°TS is the relative computed free energy of the transition state, i.e, the difference between the energy levels of the transition states for each enantiomer.

The Enantiomeric Excess '''(EE)''' is defined as '''([A]-[B])/([A]+[B]) * 100%.'''

Since K=[A]/[B], [A]=K[B], and thus, '''EE= (K[B]-[B])/K[B]+[B]) * 100%.'''

Therefore, '''EE = (K-1)/(K+1) * 100%'''

A list of possible transition states for trans-β methyl styrene using the Shi and Jacobsen's catalyst is available in digital repositories. By calculating the energy difference between the lowest energy transition state (which represents the most probably pathway for each catalytic epoxidation), ΔG°TS/RT can be calculated.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Shi Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (1)
|| -1343.032443 Ha
|-
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (2)
|| -1343.024742 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.007701 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.021897257 x 104 J/mol
|-
| K
|| 3499.272792
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfrrmethshi.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrrmethshi.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Jacobsen Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (1)
|| -3383.262481 Ha
|-
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (2)
|| -3383.254344 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.008137 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.13637x 104 J/mol
|-
| K
|| 5554.228363
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfssmethjac.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssmethjac.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

==Non-covalent Interactions in the Active-site of the Reaction Transition State==
{|
|
<jmol>
<jmolApplet>
<title>Orbital</title><color>black</color><size>300</size>
<script>isosurface color orange purple "images/5/5f/Ptf.cub.jvxl" translucent;</script>
<uploadedFileContents>ptf.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.

The NCI shown on the left was generated with the lowest energy transition state of a Jacobsen epoxidation on S,S-trans-β methyl styrene. The colours indicate whether the interaction is attractive (blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). It was observed that the alkene is aligned endo to the catalyst, allowing an attractive interaction between the phenyl group of the methyl styrene and the phenyl group of the Salen ligands, lowers the transition state energy and thus improving enantiomeric selectivity. Additionally, the two phenyl groups are also in a staggered conformation, thus minimizing steric strain. The attraction between the tBu groups also supports the hypothesis that the internuclear distance between the tBu H atoms promoted an attractive interaction.
|}

== Electronic Topology (QTAIM) in the Active-site of the Reaction Transition State==

=References=
<references />

Rep:Mod:melody

2014-03-21T15:05:13Z

Ptf11: /* Non-covalent Interactions in the Active-site of the Reaction Transition State */

=Introduction=
=Conformational analysis using Molecular Mechanics=
==The Hydrogenation of Cyclopentadiene Dimer==
===Cyclopentadiene Dimers===
Cyclopentadiene dimerises to produce specifically the endo dimer rather than the exo dimer. Using Avogadro, the two products were defined and their geometries optimised using the MMFF94(s) force field option.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcycloendo.jpg|110px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloendo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcycloexo.jpg|130px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloexo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.29872
| style="text-align: right;"|3.38094
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.42064
| style="text-align: right;"|29.06625
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-1.93752
| style="text-align: right;"|-1.89925
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.02382
| style="text-align: right;"|0.01615
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46181
| style="text-align: right;"|-1.12786
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|12.20843
| style="text-align: right;"|12.63198
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|14.05004
| style="text-align: right;"|12.90736
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|57.60233
! style="text-align: right;"|54.97559
|}
||

[[File:Ptfcyclorxnscheme.jpg|650px|thumb|Reaction mechanism for dimerisation of cyclopentadiene]]
|-
|
Although the endo product is higher in energy than the exo product by 2.63 kcal/mol, the less thermodynamically stable endo product is formed as there is stabilizing secondary orbital interaction (of the pi orbitals) in the transition state of the endo product, whereas there is no such interaction in the transition state of the exo product. The dimerisation of cyclopentadiene is thus kinetically controlled, and the endo product the kinetic product.

The energy difference between endo and exo products is largely due to the increase in the angle bending energy, with a difference of 2.35 kcal mol-1. The angle bending energy is defined as the energy involved to bend a bond away from its equilibrium angle. In the endo conformation, the ring, which is formed by joining two adjacent axial position (concave arrangement for the two rings), tends to bend upwards to the equatorial position to minimize steric hindrance with the other ring and hence causes an increase in angle bending energy. In the exo product, the ring is joined at the equatorial position (linear arrangement for the two rings) and avoids steric hindrance with the other ring, hence there is less increase in angle bending energy.
|}

===Hydrogenation===
Hydrogenation of the endo dimer proceeds to give initially one of the dihydro derivatives 3 or 4. Only after prolonged hydrogenation is the tetrahydro derivative formed.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo3.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo3.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo4.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo4.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.31116
| style="text-align: right;"|2.82326
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.93515
| style="text-align: right;"|24.68525
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-2.10212
| style="text-align: right;"|-1.65728
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.01317
| style="text-align: right;"|0.00027
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46918
| style="text-align: right;"|-0.37919
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|13.63801
| style="text-align: right;"|10.63816
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|5.11952
| style="text-align: right;"|5.14701
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|50.44571
! style="text-align: right;"|41.25748
|}
||

[[File:Ptfcyclohydrogenation.jpg|350px|thumb|Hydrogenation of cyclopentadiene endo dimer]]
|-
|
Product 4 is lower in energy than product 3 by 9.19 kcal mol-1. The difference in energy is again largely due to the angle bending energy difference of 7.25 kcal mol-1, and to a smaller extent, the Van Der Waals energy difference of 3.00 kcal mol-1 due to the greater steric repulsion in 3. The large difference in the angle bending energy is due to the geometry of the 4 sp2 carbons in the endo product of the dimer. sp2 carbons in a ring equal or smaller than 6-membered ring is generally unstable as the 120° angle favoured by sp2 centres cannot be geometrically achieved without ring strain. The double bond at the norbornene part of the molecule has sp2 carbons shared by both a 5-membered and a 6-membered ring whereas the sp2 carbons at the other end only causes ring strain to one 5-membered ring. Hence, product 4 would have more bond angles that are closer to equilibrium and hence, possesses lower ring strain and a lower angle bending energy. Product 4 should be formed as the thermodynamic product, as confirmed in literature.<ref>D. Skala and J. Hanika, "Kinetics of Dicyclopentadiene Hydrogenation Using Pd/C Catalyst", ''Pet. Coal'', '''2003''', 45, 105-108.</ref> The hydrogenation of endo dicyclopentadiene is thus thermodynamically controlled, and the the first hydrogenation occurs at the norbornene part of the molecule.
|}

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
In the total synthesis of Taxol (an important drug in the treatment of ovarian cancers), a key intermediate 9 or 10is initially synthesised with the carbonyl group pointing either up or down. By using the MMFF94(s) force field option in Avagadro, the relative stabilities of these two atropisomers were explored. After experimenting with the different conformations of intermediate 9 and 10, it was found that a "chair" conformation of both compounds 9 and 10, as shown in the table below, resulted in optimised structures with the lowest energies. The energies of the chair conformations of intermediates 9 and 10 are compared below.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo9.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo9.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo10.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo10.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|7.65248
| style="text-align: right;"|7.56126
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|28.27472
| style="text-align: right;"|18.82557
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
| style="text-align: right;"|-0.13605
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.97217
| style="text-align: right;"|0.83644
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.31893
| style="text-align: right;"|0.19401
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|33.10145
| style="text-align: right;"|33.32591
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|0.30721
| style="text-align: right;"|-0.05433
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|70.54748
! style="text-align: right;"|60.55280
|}
||

Atropisomer 10 is lower in energy, with a difference of 9.99 kcal/mol, and therefore is more thermodynamically stable than atopisomer 9. The difference in energy is largely due to the angle bending energy (9.45 kcal/mol) which makes up the majority of the total energy difference. This indicates that the bond angle of the carbonyl group in atropisomer 10 is much closer to the equilibrium angle than atopisomer 9.

This can be proven by inquiring the bond angles of the bonds involving sp2 and sp3 hybridised carbon atoms in the carbonyl group in Atropisomer 9 and 10 in Gaussview, which is summarised below.

{| class="wikitable"
! Atropisomer !! Bond Type !! Carbonyl Group Bond Angles (°) || Equilibrium Angle (°)
|-
| rowspan="2" | [[File:Ptfcyclo9.jpg|120px]] || Bonds involing sp2 hybridised carbons || 117-123 || 120
|-
| Bonds involing sp3 hybridised carbons || 100-108 || 109.5
|-
| rowspan="2" | [[File:Ptfcyclo10.jpg|120px]] || Bonds involing sp2 hybridised carbons || 120-121 || 120
|-
| Bonds involing sp3 hybridised carbons || 105-109 || 109.5
|}

Maier and Schleyer<ref name="hyper stable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. {{DOI|10.1021/ja00398a003}}</ref> concluded that double bond joined to a bridge is particularly stable due to its cage structure, thus, its corresponding hydrogenated product will experience more strain, which explains why bridgehead alkenes react slowly.

Other conformers for these atropisomers include a boat structure, which is less stable than the corresponding chair conformation. The increase in energy is due to an increase in angle bending torsional energy as the cyclohexane ring experiences greater torsional strain in the eclipsed boat conformation.
|}

=Spectroscopic Simulation using Quantum Mechanics=
==Optimization of Molecule 18==
[[File:Ptf18.jpg|thumb|Molecule 18|150px]]
{| class="wikitable" style="float: left;"
! colspan="12" align="center"|Molecule 18 Optimization
|-
| rowspan="12" align="center"|
[[File:Ptf18.jpg|150px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
! Energy
! kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|14.99958
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|30.80948
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.62729
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.89658
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|49.39433
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|-6.05522
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|100.44220
|}

The molecule 18 is a derivative of molecule 10, for which spectroscopic information has been reported.<ref name="spectra">Spectroscopic data: 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> The objective here is to simulate the 1H and 13C spectra and compare them with the literature values to see if the latter has been correctly interpreted and assigned.

Using the Avogadro or ChemBio3D program, and using the MMFF94s mechanics force field, the starting molecules 18 was optimized to an energy minimum. Based on the previous calculations involving the cyclopentadiene dimer and the Taxol intermediate atropisomer, it was predicted that the lowest energy conformation of compound 18 would be an endo (at the large ring), chair (at the smaller cyclohexane ring) conformer, as illustrated in the jmol file on the left. This structure is also supported by crystallographic data from literature.<ref name="spectra"/>

==Spectroscopic Simulation of Molecule 18==
By using Avogadro's Gaussian Geometry optimization and illustrating using GaussView, the following NMR data was obtained. The .log file of the simulation can be found [[Media:Ptf18.log|here]], and the digital repository here {{DOI|10042/28194}}.

{| class="wikitable"
!
Atom Numbering
|
[[File:Ptf18label.jpg|550px]]
| align="center" |
[[File:Ptf18simple.jpg|400px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! 1H NMR
||
[[File:Ptf18hnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
5.9943373355 1.0000 10
3.1383405979 2.0000 52,50
2.9976414945 1.0000 53
2.9268494729 2.0000 51,36
2.8117162381 2.0000 34,35
2.6103072452 1.0000 24
2.5535190605 1.0000 16
2.4785547510 1.0000 23
2.3355375185 2.0000 39,43
2.2759636135 1.0000 37
1.9983425520 2.0000 25,26
1.8486946118 2.0000 38,22
1.6500945214 1.0000 30
1.5815091205 1.0000 33
1.5179130786 2.0000 27,41
1.3617269195 1.0000 40
1.3035148468 1.0000 44
1.2231834398 2.0000 42,31
0.9508535600 3.0000 32,29,28
0.6216079526 1.0000 45
</pre>
|-
! 13C NMR
||
[[File:Ptf18cnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
213.0961325830 1.0000 11
148.0547320284 1.0000 4
120.2667148682 1.0000 9
93.3213936895 1.0000 17
65.9859553102 1.0000 13
55.0715405775 2.0000 3,12
49.7214718290 1.0000 5
48.1628662916 1.0000 18
45.8501042512 1.0000 49
44.1990174424 1.0000 48
41.3930608867 1.0000 20
38.7739494869 1.0000 8
33.7645805938 1.0000 15
32.6242885826 1.0000 14
28.4566038455 1.0000 2
26.5581305940 1.0000 6
24.6172011030 1.0000 1
24.2187982580 1.0000 19
22.6332903141 1.0000 7
</pre>
|}

The obtained spectroscopic data was then compared with literature values<ref name="spectra"/> shown below.

{| class="wikitable"
! colspan="2" | Literature Values
|-
| colspan="2" align="center" | [[File:Ptf18lit.jpg]]
|-
! 1H NMR Comparison !! 13C NMR Comparison
|-
| align="center" |[[File:Ptfhnmrcomp.jpg]]

|align="center" |
[[File:Ptfcnmrcomp.jpg]]

|-
|
[[File:Ptfhnmrcompic.jpg]]
||
[[File:Ptfcnmrcompic.jpg]]
|}

=Analysis of the Properties of Synthesised Alkene Epoxides=
==Structure of Catalsysts==
===Structure 21===
{| align="center"
| [[File:Ptf21struc.jpg|300p]] || [[File:Ptf21.jpg|500px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 21 was visualized on the Mercury program.

It was found that the six membered heteroatomic ring of structure 21 adopted a chair conformation, which was expected, to minimize torsional strain, with the Oxygen atom (O2 - with superscript 2 indicating that the atom is numbered 2) as the non-planar end. It was also discovered that substituent oxygen atoms such as O2 were in an axial position rather than the more sterically unhindered equatorial position. This allows an anti-periplanar alignment between the oxygen lone pair, which is a good donor, and the adjacent C-O2 σ* orbital which is a good acceptor, leading to a stabilising interaction. Consequently, O6 will lose electron density and the C-O2 bond lengthened as electrons are interacting with its anti-bonding orbital. The anomeric effectalso occurs in five-membered rings, but to a lesser extent due to deviations from an anti-periplanar alignment.

There are three anomeric centres present in the molecule 21, which are at C2, C9 and C10. At C2, the C2-O2 (1.423Å) bond is longer than at C2-O6 (1.415Å). At C9 and C10, C9-O2(1.454Å) and C10-O4 (1.456Å) are both longer than adjacent C9-O1(1.423Å) and C10-O5 (1.428Å) bonds. Interestingly, even though O1 and O2 appear symmetrical around C9, and similiarly for O4 and O5 around C10, only one oxygen's lone pair (O1 for C9, O5 for C10) can align in an anti-periplanar fashion to the σ* orbital of the adjacent C-O bonds. Otherwise, the mutual anomeric effects would cause each adjacent C-O bonds to be equaivalent in length.

===Structure 23===
{| align="center"
| [[File:Ptf23struc.jpg|150px]] || [[File:Ptf23.jpg|600px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 23 was visualized on the Mercury program.

Molecule 23 has a 5-coordinated manganese centre with a square pyramidal structure where 4 atoms joined by ring-like structures and bridges are coordinated to the metal center in an approximate plane, with a perpendicular chlorine atom coordinated to the metal center. This approximate planar nature is due to the delocalisation of electron densities at the salen ligands at either sides. The cyclohexane ring adopts a low energy chair conformation and has two chiral C atoms attached to N, thus defining the stereochemistry of the Jacobsen catalyst to be either (R,R) or (S,S).

The bulky tBu groups on the Salen ligands prevent a side-on approach of the alkenes due to steric hindrance, ensuring epoxidation enantioselectivity. Without the tBu groups, alkenes could have side-on approach to the catalyst, as shown when the tBu groups were replaced with methyl gourps. <ref name="10.1021/ja00018a068>E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng, ''J. Am. Chem. Soc.'', '''1991''', ''113'', 7063–7064; {{DOI|10.1021/ja00018a068}}</ref>. As seen above, the two central tBu groups are in close proximity, and the interaction between the hydrogen atoms (represented by the green lines) is an attractive interaction. The maximum attraction for non-bonded hydrogens are at 2.4Å, while repulsion only occurs when the atoms are less than 2.1Å apart from each other.<ref>M. Mantina, A. C. Chamberlin, R. Valero, C. J. Cramer, and D. G. Truhlar, "Consistent van der Waals Radii for the Whole Main Group", ''J. Phys. Chem. A'', '''2009''', 113, 5806–5812.{{DOI|10.1021/jp8111556}}</ref> This attractive interaction, coupled with the steric effects of the outer tBu groups, results in increased catalyst thermodynamic stability and selectivity.

==Simulated NMR properties of Epoxides==
===Styrene Oxide===
{| class="wikitable"
! Enantiomer !! R-Styrene oxide !! S-Styrene oxide
|-
! Labelled Structures || [[File:Ptfrsty.jpg|300px]] || [[File:Ptfssty.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrstry.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssty.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfrstry.log|.log File]]
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfssty.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfsstyhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfsstycnmr.svg|490px]]
|}

===Dihydronaphthalene Oxide===
{| class="wikitable"
! Enantiomer !! (S,R)-dihydronaphthalene oxide !! (R,S)-dihydronaphthalene oxide
|-
! Labelled Structures || [[File:Ptfsrnaph.jpg|300px]] || [[File:Ptfrsnaph.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfsrnaph.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrsnaph.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28211}} & [[Media:Ptfsrnaph.log|.log File]]
| align="center" | {{DOI|10042/28210}} & [[Media:Ptfrsnaph.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfrsnaphhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfrsnaphcnmr.svg|490px]]
|}

==Assigning the absolute configuration of the product==
===Simulated chiroptical properties===
Computational methods can be used to calculate the expected chiroptical properties of epoxides for a specified enantiomer, which can be comparing with experimental and literature values to predict the enantioselectivity of the catalyst. 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 properties can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the Imperial College 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, but the appropriate instrument is not available in the department. Thus, due to these limitations, only the optical rotation was simulated, with the following results.

{| class="wikitable"
! Epoxide !! R-Styrene oxide !! S-Styrene oxide !! (S,R)-dinaphthalene oxide !! (R,S)-dinaphthalene oxide
|-
! Simulated Optical Rotation (CHCl3, 589nm, 25°C)
| align="center" | -30.14°
| align="center" | +30.41°
| align="center" | +155.81°
| align="center" | -155.82°
|-
! Literature Optical Rotation ((CHCl3, 589nm)
| align="center" | -23.7°, 31°C<ref>E.N. Jacobsen, D.E. White, "New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions",'' Tetrahedron Asymmetry'', '''2003''', 14, 3633-3638. {{DOI|10.1016/j.tetasy.2003.09.024}}</ref>
| align="center" | +32.1°, 25°C<ref>H. Lin, J. Qiao, Y. Liu, and Z.-L. Wu, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B Enzym.'', '''2010''', 67, 236–241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref>
| align="center" | +133°<ref>D.R. Boyd, N.D. Sharma, R. Agarwal, N.A. Kerley, R.A.S. mCmORDIE, A. Smith, H. Dalton, A.J. Blacker and G.N. Sheldrake "A new synthetic route to non-K and bay region arene oxide metabolites from cis-diols", ''J. Chem. Soc., Chem. Commun.'', '''1994''', 14, 1693-1694. {{DOI|10.1039/C39940001693}}</ref>
| align="center" | -144.9°, 25°C<ref>H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki, "Rational design of Mn-salen catalyst (2): Highly enantioselective epoxidation of conjugated cis olefins", ''Tetrahedron'', '''1994''', 50, 11827-11838. {{DOI|10.1016/S0040-4020(01)89298-X}}</ref>
|-
! Digital Repository
| align="center" | {{DOI|10042/28214}}
| align="center" | {{DOI|10042/28244}}
| align="center" | {{DOI|10042/28243}}
| align="center" | {{DOI|10042/28242}}
|}

It was observed that literature values are lower than the simulated values in magnitude. This is most likely due to a less than 100% enantiomeric purity. The simulation does not take this into consideration, thus, during simulation, a 100% enantiomeric purity was assumed. Temperature could also have been a factor in the difference in optical rotation, but this effect of this difference is difficult to predict. However, the simulated and literature values seem to to be satisfactorily in agreement.

===Calculated properties of transition state for the reaction===
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. This is calculated via the Curtin-Hammett Principle, which relates the relative concentration of two products to the difference in energy of the transition states for two different conformers of a molecule. <ref>J. I. Seeman, "The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts", ''J. Chem. Educ.'',''' 1986''', 63, 42–48. {{DOI|10.1021/ed063p42}}</ref>

The principle can be simplified to the following equations;

'''K=''e''-(ΔG°TS/RT)''', where '''K=[A]/[B]''', the ratio of concentration between two conformers, and [A] and [B] are the concentrations of conformer A and B respectively, and ΔG°TS is the relative computed free energy of the transition state, i.e, the difference between the energy levels of the transition states for each enantiomer.

The Enantiomeric Excess '''(EE)''' is defined as '''([A]-[B])/([A]+[B]) * 100%.'''

Since K=[A]/[B], [A]=K[B], and thus, '''EE= (K[B]-[B])/K[B]+[B]) * 100%.'''

Therefore, '''EE = (K-1)/(K+1) * 100%'''

A list of possible transition states for trans-β methyl styrene using the Shi and Jacobsen's catalyst is available in digital repositories. By calculating the energy difference between the lowest energy transition state (which represents the most probably pathway for each catalytic epoxidation), ΔG°TS/RT can be calculated.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Shi Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (1)
|| -1343.032443 Ha
|-
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (2)
|| -1343.024742 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.007701 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.021897257 x 104 J/mol
|-
| K
|| 3499.272792
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfrrmethshi.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrrmethshi.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Jacobsen Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (1)
|| -3383.262481 Ha
|-
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (2)
|| -3383.254344 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.008137 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.13637x 104 J/mol
|-
| K
|| 5554.228363
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfssmethjac.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssmethjac.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

==Non-covalent Interactions in the Active-site of the Reaction Transition State==
{|
|
<jmol>
<jmolApplet>
<title>Orbital</title><color>black</color><size>300</size>
<script>isosurface color orange purple "images/5/5f/Ptf.cub.jvxl" translucent;</script>
<uploadedFileContents>ptf.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.

The NCI shown on the left was generated with the lowest energy transition state of a Jacobsen epoxidation on S,S-trans-β methyl styrene. The colours indicate whether the interaction is attractive (blue is very attractive, green mildly attractive, yellow mildly repulsive and red is strongly repulsive). It was observed that the alkene is aligned endo to the catalyst, allowing an attractive interaction between the phenyl group of the methyl styrene and the phenyl group of the Salen ligands, lowers the transition state energy and thus improving enantiomeric selectivity. Additionally, the two phenyl groups are also in a staggered conformation, thus minimizing steric strain. The attraction between the tBu groups also supports the hypothesis that the internuclear distance between the tBu H atoms promoted an attractive interaction.
|}

=References=
<references />

File:Ptf.cub.jvxl

2014-03-21T14:47:27Z

Ptf11:

File:Ptf.cub.xyz

2014-03-21T14:47:12Z

Ptf11:

Rep:Mod:melody

2014-03-21T14:23:05Z

Ptf11: /* Non-covalent Interactions in the Active-site of the Reaction Transition State */

=Introduction=
=Conformational analysis using Molecular Mechanics=
==The Hydrogenation of Cyclopentadiene Dimer==
===Cyclopentadiene Dimers===
Cyclopentadiene dimerises to produce specifically the endo dimer rather than the exo dimer. Using Avogadro, the two products were defined and their geometries optimised using the MMFF94(s) force field option.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcycloendo.jpg|110px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloendo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcycloexo.jpg|130px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloexo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.29872
| style="text-align: right;"|3.38094
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.42064
| style="text-align: right;"|29.06625
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-1.93752
| style="text-align: right;"|-1.89925
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.02382
| style="text-align: right;"|0.01615
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46181
| style="text-align: right;"|-1.12786
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|12.20843
| style="text-align: right;"|12.63198
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|14.05004
| style="text-align: right;"|12.90736
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|57.60233
! style="text-align: right;"|54.97559
|}
||

[[File:Ptfcyclorxnscheme.jpg|650px|thumb|Reaction mechanism for dimerisation of cyclopentadiene]]
|-
|
Although the endo product is higher in energy than the exo product by 2.63 kcal/mol, the less thermodynamically stable endo product is formed as there is stabilizing secondary orbital interaction (of the pi orbitals) in the transition state of the endo product, whereas there is no such interaction in the transition state of the exo product. The dimerisation of cyclopentadiene is thus kinetically controlled, and the endo product the kinetic product.

The energy difference between endo and exo products is largely due to the increase in the angle bending energy, with a difference of 2.35 kcal mol-1. The angle bending energy is defined as the energy involved to bend a bond away from its equilibrium angle. In the endo conformation, the ring, which is formed by joining two adjacent axial position (concave arrangement for the two rings), tends to bend upwards to the equatorial position to minimize steric hindrance with the other ring and hence causes an increase in angle bending energy. In the exo product, the ring is joined at the equatorial position (linear arrangement for the two rings) and avoids steric hindrance with the other ring, hence there is less increase in angle bending energy.
|}

===Hydrogenation===
Hydrogenation of the endo dimer proceeds to give initially one of the dihydro derivatives 3 or 4. Only after prolonged hydrogenation is the tetrahydro derivative formed.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo3.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo3.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo4.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo4.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.31116
| style="text-align: right;"|2.82326
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.93515
| style="text-align: right;"|24.68525
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-2.10212
| style="text-align: right;"|-1.65728
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.01317
| style="text-align: right;"|0.00027
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46918
| style="text-align: right;"|-0.37919
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|13.63801
| style="text-align: right;"|10.63816
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|5.11952
| style="text-align: right;"|5.14701
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|50.44571
! style="text-align: right;"|41.25748
|}
||

[[File:Ptfcyclohydrogenation.jpg|350px|thumb|Hydrogenation of cyclopentadiene endo dimer]]
|-
|
Product 4 is lower in energy than product 3 by 9.19 kcal mol-1. The difference in energy is again largely due to the angle bending energy difference of 7.25 kcal mol-1, and to a smaller extent, the Van Der Waals energy difference of 3.00 kcal mol-1 due to the greater steric repulsion in 3. The large difference in the angle bending energy is due to the geometry of the 4 sp2 carbons in the endo product of the dimer. sp2 carbons in a ring equal or smaller than 6-membered ring is generally unstable as the 120° angle favoured by sp2 centres cannot be geometrically achieved without ring strain. The double bond at the norbornene part of the molecule has sp2 carbons shared by both a 5-membered and a 6-membered ring whereas the sp2 carbons at the other end only causes ring strain to one 5-membered ring. Hence, product 4 would have more bond angles that are closer to equilibrium and hence, possesses lower ring strain and a lower angle bending energy. Product 4 should be formed as the thermodynamic product, as confirmed in literature.<ref>D. Skala and J. Hanika, "Kinetics of Dicyclopentadiene Hydrogenation Using Pd/C Catalyst", ''Pet. Coal'', '''2003''', 45, 105-108.</ref> The hydrogenation of endo dicyclopentadiene is thus thermodynamically controlled, and the the first hydrogenation occurs at the norbornene part of the molecule.
|}

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
In the total synthesis of Taxol (an important drug in the treatment of ovarian cancers), a key intermediate 9 or 10is initially synthesised with the carbonyl group pointing either up or down. By using the MMFF94(s) force field option in Avagadro, the relative stabilities of these two atropisomers were explored. After experimenting with the different conformations of intermediate 9 and 10, it was found that a "chair" conformation of both compounds 9 and 10, as shown in the table below, resulted in optimised structures with the lowest energies. The energies of the chair conformations of intermediates 9 and 10 are compared below.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo9.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo9.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo10.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo10.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|7.65248
| style="text-align: right;"|7.56126
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|28.27472
| style="text-align: right;"|18.82557
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
| style="text-align: right;"|-0.13605
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.97217
| style="text-align: right;"|0.83644
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.31893
| style="text-align: right;"|0.19401
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|33.10145
| style="text-align: right;"|33.32591
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|0.30721
| style="text-align: right;"|-0.05433
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|70.54748
! style="text-align: right;"|60.55280
|}
||

Atropisomer 10 is lower in energy, with a difference of 9.99 kcal/mol, and therefore is more thermodynamically stable than atopisomer 9. The difference in energy is largely due to the angle bending energy (9.45 kcal/mol) which makes up the majority of the total energy difference. This indicates that the bond angle of the carbonyl group in atropisomer 10 is much closer to the equilibrium angle than atopisomer 9.

This can be proven by inquiring the bond angles of the bonds involving sp2 and sp3 hybridised carbon atoms in the carbonyl group in Atropisomer 9 and 10 in Gaussview, which is summarised below.

{| class="wikitable"
! Atropisomer !! Bond Type !! Carbonyl Group Bond Angles (°) || Equilibrium Angle (°)
|-
| rowspan="2" | [[File:Ptfcyclo9.jpg|120px]] || Bonds involing sp2 hybridised carbons || 117-123 || 120
|-
| Bonds involing sp3 hybridised carbons || 100-108 || 109.5
|-
| rowspan="2" | [[File:Ptfcyclo10.jpg|120px]] || Bonds involing sp2 hybridised carbons || 120-121 || 120
|-
| Bonds involing sp3 hybridised carbons || 105-109 || 109.5
|}

Maier and Schleyer<ref name="hyper stable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. {{DOI|10.1021/ja00398a003}}</ref> concluded that double bond joined to a bridge is particularly stable due to its cage structure, thus, its corresponding hydrogenated product will experience more strain, which explains why bridgehead alkenes react slowly.

Other conformers for these atropisomers include a boat structure, which is less stable than the corresponding chair conformation. The increase in energy is due to an increase in angle bending torsional energy as the cyclohexane ring experiences greater torsional strain in the eclipsed boat conformation.
|}

=Spectroscopic Simulation using Quantum Mechanics=
==Optimization of Molecule 18==
[[File:Ptf18.jpg|thumb|Molecule 18|150px]]
{| class="wikitable" style="float: left;"
! colspan="12" align="center"|Molecule 18 Optimization
|-
| rowspan="12" align="center"|
[[File:Ptf18.jpg|150px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
! Energy
! kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|14.99958
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|30.80948
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.62729
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.89658
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|49.39433
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|-6.05522
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|100.44220
|}

The molecule 18 is a derivative of molecule 10, for which spectroscopic information has been reported.<ref name="spectra">Spectroscopic data: 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> The objective here is to simulate the 1H and 13C spectra and compare them with the literature values to see if the latter has been correctly interpreted and assigned.

Using the Avogadro or ChemBio3D program, and using the MMFF94s mechanics force field, the starting molecules 18 was optimized to an energy minimum. Based on the previous calculations involving the cyclopentadiene dimer and the Taxol intermediate atropisomer, it was predicted that the lowest energy conformation of compound 18 would be an endo (at the large ring), chair (at the smaller cyclohexane ring) conformer, as illustrated in the jmol file on the left. This structure is also supported by crystallographic data from literature.<ref name="spectra"/>

==Spectroscopic Simulation of Molecule 18==
By using Avogadro's Gaussian Geometry optimization and illustrating using GaussView, the following NMR data was obtained. The .log file of the simulation can be found [[Media:Ptf18.log|here]], and the digital repository here {{DOI|10042/28194}}.

{| class="wikitable"
!
Atom Numbering
|
[[File:Ptf18label.jpg|550px]]
| align="center" |
[[File:Ptf18simple.jpg|400px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! 1H NMR
||
[[File:Ptf18hnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
5.9943373355 1.0000 10
3.1383405979 2.0000 52,50
2.9976414945 1.0000 53
2.9268494729 2.0000 51,36
2.8117162381 2.0000 34,35
2.6103072452 1.0000 24
2.5535190605 1.0000 16
2.4785547510 1.0000 23
2.3355375185 2.0000 39,43
2.2759636135 1.0000 37
1.9983425520 2.0000 25,26
1.8486946118 2.0000 38,22
1.6500945214 1.0000 30
1.5815091205 1.0000 33
1.5179130786 2.0000 27,41
1.3617269195 1.0000 40
1.3035148468 1.0000 44
1.2231834398 2.0000 42,31
0.9508535600 3.0000 32,29,28
0.6216079526 1.0000 45
</pre>
|-
! 13C NMR
||
[[File:Ptf18cnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
213.0961325830 1.0000 11
148.0547320284 1.0000 4
120.2667148682 1.0000 9
93.3213936895 1.0000 17
65.9859553102 1.0000 13
55.0715405775 2.0000 3,12
49.7214718290 1.0000 5
48.1628662916 1.0000 18
45.8501042512 1.0000 49
44.1990174424 1.0000 48
41.3930608867 1.0000 20
38.7739494869 1.0000 8
33.7645805938 1.0000 15
32.6242885826 1.0000 14
28.4566038455 1.0000 2
26.5581305940 1.0000 6
24.6172011030 1.0000 1
24.2187982580 1.0000 19
22.6332903141 1.0000 7
</pre>
|}

The obtained spectroscopic data was then compared with literature values<ref name="spectra"/> shown below.

{| class="wikitable"
! colspan="2" | Literature Values
|-
| colspan="2" align="center" | [[File:Ptf18lit.jpg]]
|-
! 1H NMR Comparison !! 13C NMR Comparison
|-
| align="center" |[[File:Ptfhnmrcomp.jpg]]

|align="center" |
[[File:Ptfcnmrcomp.jpg]]

|-
|
[[File:Ptfhnmrcompic.jpg]]
||
[[File:Ptfcnmrcompic.jpg]]
|}

=Analysis of the Properties of Synthesised Alkene Epoxides=
==Structure of Catalsysts==
===Structure 21===
{| align="center"
| [[File:Ptf21struc.jpg|300p]] || [[File:Ptf21.jpg|500px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 21 was visualized on the Mercury program.

It was found that the six membered heteroatomic ring of structure 21 adopted a chair conformation, which was expected, to minimize torsional strain, with the Oxygen atom (O2 - with superscript 2 indicating that the atom is numbered 2) as the non-planar end. It was also discovered that substituent oxygen atoms such as O2 were in an axial position rather than the more sterically unhindered equatorial position. This allows an anti-periplanar alignment between the oxygen lone pair, which is a good donor, and the adjacent C-O2 σ* orbital which is a good acceptor, leading to a stabilising interaction. Consequently, O6 will lose electron density and the C-O2 bond lengthened as electrons are interacting with its anti-bonding orbital. The anomeric effectalso occurs in five-membered rings, but to a lesser extent due to deviations from an anti-periplanar alignment.

There are three anomeric centres present in the molecule 21, which are at C2, C9 and C10. At C2, the C2-O2 (1.423Å) bond is longer than at C2-O6 (1.415Å). At C9 and C10, C9-O2(1.454Å) and C10-O4 (1.456Å) are both longer than adjacent C9-O1(1.423Å) and C10-O5 (1.428Å) bonds. Interestingly, even though O1 and O2 appear symmetrical around C9, and similiarly for O4 and O5 around C10, only one oxygen's lone pair (O1 for C9, O5 for C10) can align in an anti-periplanar fashion to the σ* orbital of the adjacent C-O bonds. Otherwise, the mutual anomeric effects would cause each adjacent C-O bonds to be equaivalent in length.

===Structure 23===
{| align="center"
| [[File:Ptf23struc.jpg|150px]] || [[File:Ptf23.jpg|600px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 23 was visualized on the Mercury program.

Molecule 23 has a 5-coordinated manganese centre with a square pyramidal structure where 4 atoms joined by ring-like structures and bridges are coordinated to the metal center in an approximate plane, with a perpendicular chlorine atom coordinated to the metal center. This approximate planar nature is due to the delocalisation of electron densities at the salen ligands at either sides. The cyclohexane ring adopts a low energy chair conformation and has two chiral C atoms attached to N, thus defining the stereochemistry of the Jacobsen catalyst to be either (R,R) or (S,S).

The bulky tBu groups on the Salen ligands prevent a side-on approach of the alkenes due to steric hindrance, ensuring epoxidation enantioselectivity. Without the tBu groups, alkenes could have side-on approach to the catalyst, as shown when the tBu groups were replaced with methyl gourps. <ref name="10.1021/ja00018a068>E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng, ''J. Am. Chem. Soc.'', '''1991''', ''113'', 7063–7064; {{DOI|10.1021/ja00018a068}}</ref>. As seen above, the two central tBu groups are in close proximity, and the interaction between the hydrogen atoms (represented by the green lines) is an attractive interaction. The maximum attraction for non-bonded hydrogens are at 2.4Å, while repulsion only occurs when the atoms are less than 2.1Å apart from each other.<ref>M. Mantina, A. C. Chamberlin, R. Valero, C. J. Cramer, and D. G. Truhlar, "Consistent van der Waals Radii for the Whole Main Group", ''J. Phys. Chem. A'', '''2009''', 113, 5806–5812.{{DOI|10.1021/jp8111556}}</ref> This attractive interaction, coupled with the steric effects of the outer tBu groups, results in increased catalyst thermodynamic stability and selectivity.

==Simulated NMR properties of Epoxides==
===Styrene Oxide===
{| class="wikitable"
! Enantiomer !! R-Styrene oxide !! S-Styrene oxide
|-
! Labelled Structures || [[File:Ptfrsty.jpg|300px]] || [[File:Ptfssty.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrstry.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssty.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfrstry.log|.log File]]
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfssty.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfsstyhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfsstycnmr.svg|490px]]
|}

===Dihydronaphthalene Oxide===
{| class="wikitable"
! Enantiomer !! (S,R)-dihydronaphthalene oxide !! (R,S)-dihydronaphthalene oxide
|-
! Labelled Structures || [[File:Ptfsrnaph.jpg|300px]] || [[File:Ptfrsnaph.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfsrnaph.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrsnaph.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28211}} & [[Media:Ptfsrnaph.log|.log File]]
| align="center" | {{DOI|10042/28210}} & [[Media:Ptfrsnaph.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfrsnaphhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfrsnaphcnmr.svg|490px]]
|}

==Assigning the absolute configuration of the product==
===Simulated chiroptical properties===
Computational methods can be used to calculate the expected chiroptical properties of epoxides for a specified enantiomer, which can be comparing with experimental and literature values to predict the enantioselectivity of the catalyst. 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 properties can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the Imperial College 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, but the appropriate instrument is not available in the department. Thus, due to these limitations, only the optical rotation was simulated, with the following results.

{| class="wikitable"
! Epoxide !! R-Styrene oxide !! S-Styrene oxide !! (S,R)-dinaphthalene oxide !! (R,S)-dinaphthalene oxide
|-
! Simulated Optical Rotation (CHCl3, 589nm, 25°C)
| align="center" | -30.14°
| align="center" | +30.41°
| align="center" | +155.81°
| align="center" | -155.82°
|-
! Literature Optical Rotation ((CHCl3, 589nm)
| align="center" | -23.7°, 31°C<ref>E.N. Jacobsen, D.E. White, "New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions",'' Tetrahedron Asymmetry'', '''2003''', 14, 3633-3638. {{DOI|10.1016/j.tetasy.2003.09.024}}</ref>
| align="center" | +32.1°, 25°C<ref>H. Lin, J. Qiao, Y. Liu, and Z.-L. Wu, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B Enzym.'', '''2010''', 67, 236–241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref>
| align="center" | +133°<ref>D.R. Boyd, N.D. Sharma, R. Agarwal, N.A. Kerley, R.A.S. mCmORDIE, A. Smith, H. Dalton, A.J. Blacker and G.N. Sheldrake "A new synthetic route to non-K and bay region arene oxide metabolites from cis-diols", ''J. Chem. Soc., Chem. Commun.'', '''1994''', 14, 1693-1694. {{DOI|10.1039/C39940001693}}</ref>
| align="center" | -144.9°, 25°C<ref>H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki, "Rational design of Mn-salen catalyst (2): Highly enantioselective epoxidation of conjugated cis olefins", ''Tetrahedron'', '''1994''', 50, 11827-11838. {{DOI|10.1016/S0040-4020(01)89298-X}}</ref>
|-
! Digital Repository
| align="center" | {{DOI|10042/28214}}
| align="center" | {{DOI|10042/28244}}
| align="center" | {{DOI|10042/28243}}
| align="center" | {{DOI|10042/28242}}
|}

It was observed that literature values are lower than the simulated values in magnitude. This is most likely due to a less than 100% enantiomeric purity. The simulation does not take this into consideration, thus, during simulation, a 100% enantiomeric purity was assumed. Temperature could also have been a factor in the difference in optical rotation, but this effect of this difference is difficult to predict. However, the simulated and literature values seem to to be satisfactorily in agreement.

===Calculated properties of transition state for the reaction===
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. This is calculated via the Curtin-Hammett Principle, which relates the relative concentration of two products to the difference in energy of the transition states for two different conformers of a molecule. <ref>J. I. Seeman, "The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts", ''J. Chem. Educ.'',''' 1986''', 63, 42–48. {{DOI|10.1021/ed063p42}}</ref>

The principle can be simplified to the following equations;

'''K=''e''-(ΔG°TS/RT)''', where '''K=[A]/[B]''', the ratio of concentration between two conformers, and [A] and [B] are the concentrations of conformer A and B respectively, and ΔG°TS is the relative computed free energy of the transition state, i.e, the difference between the energy levels of the transition states for each enantiomer.

The Enantiomeric Excess '''(EE)''' is defined as '''([A]-[B])/([A]+[B]) * 100%.'''

Since K=[A]/[B], [A]=K[B], and thus, '''EE= (K[B]-[B])/K[B]+[B]) * 100%.'''

Therefore, '''EE = (K-1)/(K+1) * 100%'''

A list of possible transition states for trans-β methyl styrene using the Shi and Jacobsen's catalyst is available in digital repositories. By calculating the energy difference between the lowest energy transition state (which represents the most probably pathway for each catalytic epoxidation), ΔG°TS/RT can be calculated.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Shi Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (1)
|| -1343.032443 Ha
|-
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (2)
|| -1343.024742 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.007701 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.021897257 x 104 J/mol
|-
| K
|| 3499.272792
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfrrmethshi.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrrmethshi.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Jacobsen Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (1)
|| -3383.262481 Ha
|-
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (2)
|| -3383.254344 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.008137 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.13637x 104 J/mol
|-
| K
|| 5554.228363
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfssmethjac.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssmethjac.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

==Non-covalent Interactions in the Active-site of the Reaction Transition State==
<jmol>
<jmolApplet>
<title>Orbital</title><color>black</color><size>300</size>
<script>isosurface color orange purple "images/7/75/Ptfnci.cub.jvxl" translucent;</script>
<uploadedFileContents>Ptfnci.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>

=References=
<references />

Rep:Mod:melody

2014-03-21T14:14:53Z

Ptf11: /* References */

=Introduction=
=Conformational analysis using Molecular Mechanics=
==The Hydrogenation of Cyclopentadiene Dimer==
===Cyclopentadiene Dimers===
Cyclopentadiene dimerises to produce specifically the endo dimer rather than the exo dimer. Using Avogadro, the two products were defined and their geometries optimised using the MMFF94(s) force field option.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcycloendo.jpg|110px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloendo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcycloexo.jpg|130px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcycloexo.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.29872
| style="text-align: right;"|3.38094
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.42064
| style="text-align: right;"|29.06625
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-1.93752
| style="text-align: right;"|-1.89925
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.02382
| style="text-align: right;"|0.01615
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46181
| style="text-align: right;"|-1.12786
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|12.20843
| style="text-align: right;"|12.63198
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|14.05004
| style="text-align: right;"|12.90736
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|57.60233
! style="text-align: right;"|54.97559
|}
||

[[File:Ptfcyclorxnscheme.jpg|650px|thumb|Reaction mechanism for dimerisation of cyclopentadiene]]
|-
|
Although the endo product is higher in energy than the exo product by 2.63 kcal/mol, the less thermodynamically stable endo product is formed as there is stabilizing secondary orbital interaction (of the pi orbitals) in the transition state of the endo product, whereas there is no such interaction in the transition state of the exo product. The dimerisation of cyclopentadiene is thus kinetically controlled, and the endo product the kinetic product.

The energy difference between endo and exo products is largely due to the increase in the angle bending energy, with a difference of 2.35 kcal mol-1. The angle bending energy is defined as the energy involved to bend a bond away from its equilibrium angle. In the endo conformation, the ring, which is formed by joining two adjacent axial position (concave arrangement for the two rings), tends to bend upwards to the equatorial position to minimize steric hindrance with the other ring and hence causes an increase in angle bending energy. In the exo product, the ring is joined at the equatorial position (linear arrangement for the two rings) and avoids steric hindrance with the other ring, hence there is less increase in angle bending energy.
|}

===Hydrogenation===
Hydrogenation of the endo dimer proceeds to give initially one of the dihydro derivatives 3 or 4. Only after prolonged hydrogenation is the tetrahydro derivative formed.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo3.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo3.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo4.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo4.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|3.31116
| style="text-align: right;"|2.82326
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|31.93515
| style="text-align: right;"|24.68525
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-2.10212
| style="text-align: right;"|-1.65728
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.01317
| style="text-align: right;"|0.00027
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|-1.46918
| style="text-align: right;"|-0.37919
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|13.63801
| style="text-align: right;"|10.63816
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|5.11952
| style="text-align: right;"|5.14701
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|50.44571
! style="text-align: right;"|41.25748
|}
||

[[File:Ptfcyclohydrogenation.jpg|350px|thumb|Hydrogenation of cyclopentadiene endo dimer]]
|-
|
Product 4 is lower in energy than product 3 by 9.19 kcal mol-1. The difference in energy is again largely due to the angle bending energy difference of 7.25 kcal mol-1, and to a smaller extent, the Van Der Waals energy difference of 3.00 kcal mol-1 due to the greater steric repulsion in 3. The large difference in the angle bending energy is due to the geometry of the 4 sp2 carbons in the endo product of the dimer. sp2 carbons in a ring equal or smaller than 6-membered ring is generally unstable as the 120° angle favoured by sp2 centres cannot be geometrically achieved without ring strain. The double bond at the norbornene part of the molecule has sp2 carbons shared by both a 5-membered and a 6-membered ring whereas the sp2 carbons at the other end only causes ring strain to one 5-membered ring. Hence, product 4 would have more bond angles that are closer to equilibrium and hence, possesses lower ring strain and a lower angle bending energy. Product 4 should be formed as the thermodynamic product, as confirmed in literature.<ref>D. Skala and J. Hanika, "Kinetics of Dicyclopentadiene Hydrogenation Using Pd/C Catalyst", ''Pet. Coal'', '''2003''', 45, 105-108.</ref> The hydrogenation of endo dicyclopentadiene is thus thermodynamically controlled, and the the first hydrogenation occurs at the norbornene part of the molecule.
|}

==Atropisomerism in an Intermediate related to the Synthesis of Taxol==
In the total synthesis of Taxol (an important drug in the treatment of ovarian cancers), a key intermediate 9 or 10is initially synthesised with the carbonyl group pointing either up or down. By using the MMFF94(s) force field option in Avagadro, the relative stabilities of these two atropisomers were explored. After experimenting with the different conformations of intermediate 9 and 10, it was found that a "chair" conformation of both compounds 9 and 10, as shown in the table below, resulted in optimised structures with the lowest energies. The energies of the chair conformations of intermediates 9 and 10 are compared below.
{|
{| class="wikitable" border="1" style="float: left;"
! colspan="3" align="center"|Cyclopentadiene Dimer Comparison
|-
! Diastereoisomer
| align="center"|
[[File:Ptfcyclo9.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo9.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center"|
[[File:Ptfcyclo10.jpg|120px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>ptfcyclo10.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! style="text-align: left;"|Energy
! colspan="2" |kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|7.65248
| style="text-align: right;"|7.56126
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|28.27472
| style="text-align: right;"|18.82557
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
| style="text-align: right;"|-0.13605
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.97217
| style="text-align: right;"|0.83644
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.31893
| style="text-align: right;"|0.19401
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|33.10145
| style="text-align: right;"|33.32591
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|0.30721
| style="text-align: right;"|-0.05433
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|70.54748
! style="text-align: right;"|60.55280
|}
||

Atropisomer 10 is lower in energy, with a difference of 9.99 kcal/mol, and therefore is more thermodynamically stable than atopisomer 9. The difference in energy is largely due to the angle bending energy (9.45 kcal/mol) which makes up the majority of the total energy difference. This indicates that the bond angle of the carbonyl group in atropisomer 10 is much closer to the equilibrium angle than atopisomer 9.

This can be proven by inquiring the bond angles of the bonds involving sp2 and sp3 hybridised carbon atoms in the carbonyl group in Atropisomer 9 and 10 in Gaussview, which is summarised below.

{| class="wikitable"
! Atropisomer !! Bond Type !! Carbonyl Group Bond Angles (°) || Equilibrium Angle (°)
|-
| rowspan="2" | [[File:Ptfcyclo9.jpg|120px]] || Bonds involing sp2 hybridised carbons || 117-123 || 120
|-
| Bonds involing sp3 hybridised carbons || 100-108 || 109.5
|-
| rowspan="2" | [[File:Ptfcyclo10.jpg|120px]] || Bonds involing sp2 hybridised carbons || 120-121 || 120
|-
| Bonds involing sp3 hybridised carbons || 105-109 || 109.5
|}

Maier and Schleyer<ref name="hyper stable">W. F. Maier, P. Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. {{DOI|10.1021/ja00398a003}}</ref> concluded that double bond joined to a bridge is particularly stable due to its cage structure, thus, its corresponding hydrogenated product will experience more strain, which explains why bridgehead alkenes react slowly.

Other conformers for these atropisomers include a boat structure, which is less stable than the corresponding chair conformation. The increase in energy is due to an increase in angle bending torsional energy as the cyclohexane ring experiences greater torsional strain in the eclipsed boat conformation.
|}

=Spectroscopic Simulation using Quantum Mechanics=
==Optimization of Molecule 18==
[[File:Ptf18.jpg|thumb|Molecule 18|150px]]
{| class="wikitable" style="float: left;"
! colspan="12" align="center"|Molecule 18 Optimization
|-
| rowspan="12" align="center"|
[[File:Ptf18.jpg|150px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
! Energy
! kcal mol-1
|-
| style="text-align: left;"|Stretching
| style="text-align: right;"|14.99958
|-
| style="text-align: left;"|Angle Bending
| style="text-align: right;"|30.80948
|-
| style="text-align: left;"|Stretch Bending
| style="text-align: right;"|-0.07951
|-
| style="text-align: left;"|Out-of-plane Bending
| style="text-align: right;"|0.62729
|-
| style="text-align: left;"|Torsion
| style="text-align: right;"|0.89658
|-
| style="text-align: left;"|Van der Waals
| style="text-align: right;"|49.39433
|-
| style="text-align: left;"|Electrostatic
| style="text-align: right;"|-6.05522
|-
! style="text-align: left;"|Total Energy
! style="text-align: right;"|100.44220
|}

The molecule 18 is a derivative of molecule 10, for which spectroscopic information has been reported.<ref name="spectra">Spectroscopic data: 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> The objective here is to simulate the 1H and 13C spectra and compare them with the literature values to see if the latter has been correctly interpreted and assigned.

Using the Avogadro or ChemBio3D program, and using the MMFF94s mechanics force field, the starting molecules 18 was optimized to an energy minimum. Based on the previous calculations involving the cyclopentadiene dimer and the Taxol intermediate atropisomer, it was predicted that the lowest energy conformation of compound 18 would be an endo (at the large ring), chair (at the smaller cyclohexane ring) conformer, as illustrated in the jmol file on the left. This structure is also supported by crystallographic data from literature.<ref name="spectra"/>

==Spectroscopic Simulation of Molecule 18==
By using Avogadro's Gaussian Geometry optimization and illustrating using GaussView, the following NMR data was obtained. The .log file of the simulation can be found [[Media:Ptf18.log|here]], and the digital repository here {{DOI|10042/28194}}.

{| class="wikitable"
!
Atom Numbering
|
[[File:Ptf18label.jpg|550px]]
| align="center" |
[[File:Ptf18simple.jpg|400px]]

<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptf18.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! 1H NMR
||
[[File:Ptf18hnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
5.9943373355 1.0000 10
3.1383405979 2.0000 52,50
2.9976414945 1.0000 53
2.9268494729 2.0000 51,36
2.8117162381 2.0000 34,35
2.6103072452 1.0000 24
2.5535190605 1.0000 16
2.4785547510 1.0000 23
2.3355375185 2.0000 39,43
2.2759636135 1.0000 37
1.9983425520 2.0000 25,26
1.8486946118 2.0000 38,22
1.6500945214 1.0000 30
1.5815091205 1.0000 33
1.5179130786 2.0000 27,41
1.3617269195 1.0000 40
1.3035148468 1.0000 44
1.2231834398 2.0000 42,31
0.9508535600 3.0000 32,29,28
0.6216079526 1.0000 45
</pre>
|-
! 13C NMR
||
[[File:Ptf18cnmr.svg|550px]]
||
<pre>
Shift (ppm) Degeneracy Atoms
213.0961325830 1.0000 11
148.0547320284 1.0000 4
120.2667148682 1.0000 9
93.3213936895 1.0000 17
65.9859553102 1.0000 13
55.0715405775 2.0000 3,12
49.7214718290 1.0000 5
48.1628662916 1.0000 18
45.8501042512 1.0000 49
44.1990174424 1.0000 48
41.3930608867 1.0000 20
38.7739494869 1.0000 8
33.7645805938 1.0000 15
32.6242885826 1.0000 14
28.4566038455 1.0000 2
26.5581305940 1.0000 6
24.6172011030 1.0000 1
24.2187982580 1.0000 19
22.6332903141 1.0000 7
</pre>
|}

The obtained spectroscopic data was then compared with literature values<ref name="spectra"/> shown below.

{| class="wikitable"
! colspan="2" | Literature Values
|-
| colspan="2" align="center" | [[File:Ptf18lit.jpg]]
|-
! 1H NMR Comparison !! 13C NMR Comparison
|-
| align="center" |[[File:Ptfhnmrcomp.jpg]]

|align="center" |
[[File:Ptfcnmrcomp.jpg]]

|-
|
[[File:Ptfhnmrcompic.jpg]]
||
[[File:Ptfcnmrcompic.jpg]]
|}

=Analysis of the Properties of Synthesised Alkene Epoxides=
==Structure of Catalsysts==
===Structure 21===
{| align="center"
| [[File:Ptf21struc.jpg|300p]] || [[File:Ptf21.jpg|500px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 21 was visualized on the Mercury program.

It was found that the six membered heteroatomic ring of structure 21 adopted a chair conformation, which was expected, to minimize torsional strain, with the Oxygen atom (O2 - with superscript 2 indicating that the atom is numbered 2) as the non-planar end. It was also discovered that substituent oxygen atoms such as O2 were in an axial position rather than the more sterically unhindered equatorial position. This allows an anti-periplanar alignment between the oxygen lone pair, which is a good donor, and the adjacent C-O2 σ* orbital which is a good acceptor, leading to a stabilising interaction. Consequently, O6 will lose electron density and the C-O2 bond lengthened as electrons are interacting with its anti-bonding orbital. The anomeric effectalso occurs in five-membered rings, but to a lesser extent due to deviations from an anti-periplanar alignment.

There are three anomeric centres present in the molecule 21, which are at C2, C9 and C10. At C2, the C2-O2 (1.423Å) bond is longer than at C2-O6 (1.415Å). At C9 and C10, C9-O2(1.454Å) and C10-O4 (1.456Å) are both longer than adjacent C9-O1(1.423Å) and C10-O5 (1.428Å) bonds. Interestingly, even though O1 and O2 appear symmetrical around C9, and similiarly for O4 and O5 around C10, only one oxygen's lone pair (O1 for C9, O5 for C10) can align in an anti-periplanar fashion to the σ* orbital of the adjacent C-O bonds. Otherwise, the mutual anomeric effects would cause each adjacent C-O bonds to be equaivalent in length.

===Structure 23===
{| align="center"
| [[File:Ptf23struc.jpg|150px]] || [[File:Ptf23.jpg|600px]]
|}

Based on the Cambridge crystal database (CCDC) using the Conquest program, molecule 23 was visualized on the Mercury program.

Molecule 23 has a 5-coordinated manganese centre with a square pyramidal structure where 4 atoms joined by ring-like structures and bridges are coordinated to the metal center in an approximate plane, with a perpendicular chlorine atom coordinated to the metal center. This approximate planar nature is due to the delocalisation of electron densities at the salen ligands at either sides. The cyclohexane ring adopts a low energy chair conformation and has two chiral C atoms attached to N, thus defining the stereochemistry of the Jacobsen catalyst to be either (R,R) or (S,S).

The bulky tBu groups on the Salen ligands prevent a side-on approach of the alkenes due to steric hindrance, ensuring epoxidation enantioselectivity. Without the tBu groups, alkenes could have side-on approach to the catalyst, as shown when the tBu groups were replaced with methyl gourps. <ref name="10.1021/ja00018a068>E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng, ''J. Am. Chem. Soc.'', '''1991''', ''113'', 7063–7064; {{DOI|10.1021/ja00018a068}}</ref>. As seen above, the two central tBu groups are in close proximity, and the interaction between the hydrogen atoms (represented by the green lines) is an attractive interaction. The maximum attraction for non-bonded hydrogens are at 2.4Å, while repulsion only occurs when the atoms are less than 2.1Å apart from each other.<ref>M. Mantina, A. C. Chamberlin, R. Valero, C. J. Cramer, and D. G. Truhlar, "Consistent van der Waals Radii for the Whole Main Group", ''J. Phys. Chem. A'', '''2009''', 113, 5806–5812.{{DOI|10.1021/jp8111556}}</ref> This attractive interaction, coupled with the steric effects of the outer tBu groups, results in increased catalyst thermodynamic stability and selectivity.

==Simulated NMR properties of Epoxides==
===Styrene Oxide===
{| class="wikitable"
! Enantiomer !! R-Styrene oxide !! S-Styrene oxide
|-
! Labelled Structures || [[File:Ptfrsty.jpg|300px]] || [[File:Ptfssty.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrstry.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssty.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfrstry.log|.log File]]
| align="center" | {{DOI|10042/28208}} & [[Media:Ptfssty.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfsstyhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfsstycnmr.svg|490px]]
|}

===Dihydronaphthalene Oxide===
{| class="wikitable"
! Enantiomer !! (S,R)-dihydronaphthalene oxide !! (R,S)-dihydronaphthalene oxide
|-
! Labelled Structures || [[File:Ptfsrnaph.jpg|300px]] || [[File:Ptfrsnaph.jpg|300px]]
|-
! 3D Structures
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfsrnaph.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
| align="center" | <jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrsnaph.mol</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|-
! Digital Repository
| align="center" | {{DOI|10042/28211}} & [[Media:Ptfsrnaph.log|.log File]]
| align="center" | {{DOI|10042/28210}} & [[Media:Ptfrsnaph.log|.log File]]
|-
! Simulated 1H NMR
|| [[File:Ptfrsty.svg|490px]]
|| [[File:Ptfrsnaphhnmr.svg|490px]]
|-
! Simulated 13C NMR
|| [[File:Ptfrstycnmr.svg|490px]]
|| [[File:Ptfrsnaphcnmr.svg|490px]]
|}

==Assigning the absolute configuration of the product==
===Simulated chiroptical properties===
Computational methods can be used to calculate the expected chiroptical properties of epoxides for a specified enantiomer, which can be comparing with experimental and literature values to predict the enantioselectivity of the catalyst. 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 properties can be computed nowadays. However, only the first (the optical rotation) can be readily measured in the Imperial College 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, but the appropriate instrument is not available in the department. Thus, due to these limitations, only the optical rotation was simulated, with the following results.

{| class="wikitable"
! Epoxide !! R-Styrene oxide !! S-Styrene oxide !! (S,R)-dinaphthalene oxide !! (R,S)-dinaphthalene oxide
|-
! Simulated Optical Rotation (CHCl3, 589nm, 25°C)
| align="center" | -30.14°
| align="center" | +30.41°
| align="center" | +155.81°
| align="center" | -155.82°
|-
! Literature Optical Rotation ((CHCl3, 589nm)
| align="center" | -23.7°, 31°C<ref>E.N. Jacobsen, D.E. White, "New oligomeric catalyst for the hydrolytic kinetic resolution of terminal epoxides under solvent-free conditions",'' Tetrahedron Asymmetry'', '''2003''', 14, 3633-3638. {{DOI|10.1016/j.tetasy.2003.09.024}}</ref>
| align="center" | +32.1°, 25°C<ref>H. Lin, J. Qiao, Y. Liu, and Z.-L. Wu, "Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes", ''J. Mol. Catal. B Enzym.'', '''2010''', 67, 236–241. {{DOI|10.1016/j.molcatb.2010.08.012}}</ref>
| align="center" | +133°<ref>D.R. Boyd, N.D. Sharma, R. Agarwal, N.A. Kerley, R.A.S. mCmORDIE, A. Smith, H. Dalton, A.J. Blacker and G.N. Sheldrake "A new synthetic route to non-K and bay region arene oxide metabolites from cis-diols", ''J. Chem. Soc., Chem. Commun.'', '''1994''', 14, 1693-1694. {{DOI|10.1039/C39940001693}}</ref>
| align="center" | -144.9°, 25°C<ref>H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki, "Rational design of Mn-salen catalyst (2): Highly enantioselective epoxidation of conjugated cis olefins", ''Tetrahedron'', '''1994''', 50, 11827-11838. {{DOI|10.1016/S0040-4020(01)89298-X}}</ref>
|-
! Digital Repository
| align="center" | {{DOI|10042/28214}}
| align="center" | {{DOI|10042/28244}}
| align="center" | {{DOI|10042/28243}}
| align="center" | {{DOI|10042/28242}}
|}

It was observed that literature values are lower than the simulated values in magnitude. This is most likely due to a less than 100% enantiomeric purity. The simulation does not take this into consideration, thus, during simulation, a 100% enantiomeric purity was assumed. Temperature could also have been a factor in the difference in optical rotation, but this effect of this difference is difficult to predict. However, the simulated and literature values seem to to be satisfactorily in agreement.

===Calculated properties of transition state for the reaction===
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. This is calculated via the Curtin-Hammett Principle, which relates the relative concentration of two products to the difference in energy of the transition states for two different conformers of a molecule. <ref>J. I. Seeman, "The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts", ''J. Chem. Educ.'',''' 1986''', 63, 42–48. {{DOI|10.1021/ed063p42}}</ref>

The principle can be simplified to the following equations;

'''K=''e''-(ΔG°TS/RT)''', where '''K=[A]/[B]''', the ratio of concentration between two conformers, and [A] and [B] are the concentrations of conformer A and B respectively, and ΔG°TS is the relative computed free energy of the transition state, i.e, the difference between the energy levels of the transition states for each enantiomer.

The Enantiomeric Excess '''(EE)''' is defined as '''([A]-[B])/([A]+[B]) * 100%.'''

Since K=[A]/[B], [A]=K[B], and thus, '''EE= (K[B]-[B])/K[B]+[B]) * 100%.'''

Therefore, '''EE = (K-1)/(K+1) * 100%'''

A list of possible transition states for trans-β methyl styrene using the Shi and Jacobsen's catalyst is available in digital repositories. By calculating the energy difference between the lowest energy transition state (which represents the most probably pathway for each catalytic epoxidation), ΔG°TS/RT can be calculated.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Shi Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (1)
|| -1343.032443 Ha
|-
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (2)
|| -1343.024742 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.007701 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.021897257 x 104 J/mol
|-
| K
|| 3499.272792
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfrrmethshi.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfrrmethshi.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

===Calculated Enantiomeric excess of Trans-β methyl styrene using Jacobsen Catalyst===
{|
|
{| class="wikitable"
| Free Energy of lowest (S,S)-Trans-β-methyl Styrene Oxide TS (1)
|| -3383.262481 Ha
|-
| Free Energy of lowest (R,R)-Trans-β-methyl Styrene Oxide TS (2)
|| -3383.254344 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -0.008137 Ha
|-
| ΔGTS (1)-(2)=(3)
|| -2.13637x 104 J/mol
|-
| K
|| 5554.228363
|-
| Enantiomeric Excess
|| 99.9%
|}
||
[[File:Ptfssmethjac.jpg|thumb|Lowest Energy (R,R)-Trans-β-methyl Styrene Oxide TS |200px]]
| align="center" |
<jmol>
<jmolAppletButton>
<uploadedFileContents>Ptfssmethjac.mol2</uploadedFileContents>
<text>Jmol File</text>
</jmolAppletButton>
</jmol>
|}
While, the calculation has overestimated the enantiomeric excess of the (R,R)-Trans-β-methyl Styrene Oxide enantiomer (99.9%), when compared to literature values of 93.2% <ref>Z. Wang, Y. Tu, M. Frohn, J. Zhang and Y. Shi, "An Efficient Catalytic Asymmetric Epoxidation Method", ''J. Am. Chem. Soc.'', '''1997''', 119, 11224-11235. {{DOI|10.1021/ja972272g}}</ref>, it is in general agreement that the R,R enantiomer is largely the major product.

==Non-covalent Interactions in the Active-site of the Reaction Transition State==
<jmol>
<jmolApplet>
<title>Orbital</title><color>black</color><size>300</size>
<script>isosurface color orange purple "images/3/3f/Ptfnci.cub.jvxl" translucent;</script>
<uploadedFileContents>Ptfnci.cub.xyz</uploadedFileContents>
</jmolApplet>
</jmol>
=References=
<references />

2014-03-21T10:41:39Z

Ptf11: /* References */

Rep:Mod:melody

2014-03-21T10:30:54Z

Ptf11: /* Structure 23 */

Rep:Mod:melody

2014-03-21T10:30:39Z

Ptf11: /* Simulated NMR properties of your epoxides */

Rep:Mod:melody

2014-03-21T10:30:15Z

Ptf11: /* Analysis of the Properties of Synthesised Alkene Epoxides */