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Rep:Mod:OJA692728

2013-11-22T15:37:00Z

Oa1811: /* NCI & QTAIM */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimize both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy (kcal/mol) !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the 6-membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hindrance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s force field the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuration of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHz whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A2 the ring structure is distorted due to it being fused to the central 6-membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5-membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivity to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for Styrene oxide have been tabulated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg|Spectra]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optimized Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for trans-Stilbene oxide have been tabulated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg|Spectra]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the transition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimentary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substitution on the alkene that leads to such poor selectivity in comparison to tri-substituted alkenes where the selectivity with the Shi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of substituent on the terminal alkene in styrene results in poor selectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. For other terminal alkenes it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studies into the epoxidation of terminal alkenes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epoxide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

All of the non-bond BCPs in the [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] are about central indicating a balanced contribution from both atoms involved, and the majority of these are H-bonds so an equal contribution is expected. Interestingly the Shi Catalyst has a couple of intr-amolecular BCPs which could explain the stability of this catalyst and its selectivity. The terminal Hydrogen has two non-bonding BCPs to the catalysis which demonstrate the catalyst's selectivity mechanism being based upon steric interactions. If these hydrogens were replaced with larger groups than stronger interactions would be seen here.

==Other Candidates==
[[Media:OJA_Chrysene_Candidate.png|Chrysene]] is another molecule that could be investigated and is readily available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and has an ORD of 9. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst or one based on similar foundations.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T15:27:59Z

Oa1811: /* Other Candidates */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimize both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy (kcal/mol) !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the 6-membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hindrance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s force field the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuration of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHz whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A2 the ring structure is distorted due to it being fused to the central 6-membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5-membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivity to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for Styrene oxide have been tabulated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg|Spectra]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optimized Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for trans-Stilbene oxide have been tabulated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg|Spectra]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the transition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimentary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substitution on the alkene that leads to such poor selectivity in comparison to tri-substituted alkenes where the selectivity with the Shi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of substituent on the terminal alkene in styrene results in poor selectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. For other terminal alkenes it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studies into the epoxidation of terminal alkenes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epoxide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
[[Media:OJA_Chrysene_Candidate.png|Chrysene]] is another molecule that could be investigated and is readily available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and has an ORD of 9. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst or one based on similar foundations.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T15:06:36Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimize both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy (kcal/mol) !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the 6-membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hindrance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s force field the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuration of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHz whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A2 the ring structure is distorted due to it being fused to the central 6-membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5-membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivity to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for Styrene oxide have been tabulated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg|Spectra]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optimized Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for trans-Stilbene oxide have been tabulated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg|Spectra]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the transition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimentary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substitution on the alkene that leads to such poor selectivity in comparison to tri-substituted alkenes where the selectivity with the Shi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of substituent on the terminal alkene in styrene results in poor selectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. For other terminal alkenes it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studies into the epoxidation of terminal alkenes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epoxide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T13:13:38Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimize both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for Styrene oxide have been tabulated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg|Spectra]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optimized Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for trans-Stilbene oxide have been tabulated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg|Spectra]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T13:09:41Z

Oa1811: /* NMR */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for Styrene oxide have been tabulated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg|Spectra]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optimized Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature findings for trans-Stilbene oxide have been tabulated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg|Spectra]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg|Spectra]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T13:07:46Z

Oa1811: /* Spectroscopic Simulation using Quantum Mechanics */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish it's NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg|Spectra]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg|Spectra]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T12:43:30Z

Oa1811: /* Catalysts */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T11:42:48Z

Oa1811: /* NCI & QTAIM */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

As can be seen in the Jmol there is no blue surface between the catalyst and Styrene showing that there isn't a large amount of strongly attractive forces between the two. There is a small patch of blue on the ring which is between the new -C-O- bond. The attractive interactions between the methyl groups of the catalyst with Styrene can clearly be seen by the green surface between them has slight yellow tones indicating that this dispersion is not entirely attractive.

In comparison with the QTAIM where there are strong green surfaces where a BCPs are found, showing the validity of the two calculations. However the lack of co-ordinates available for the QTAIM make it difficult to quantitatively compare the two. Qualitatively though H-Bonds can be seen between the Oxygen and Hyrdrogens on the catalyst.

The main area of dispersion is between the alkene and A1 anomeric centre leading to the spiro transition state as expected<ref name=ShiCatalystOriginal />. The lack of substitution on the double bond results in little interaction at the terminal end of the alkene with the catalyst, perhaps indicative of the poor selectivity for this reaction; if the catalyst could interact with an area of steric bulk it would be more selective towards one enantiomer due to the attractive forces between the two molecules.

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T11:11:30Z

Oa1811: /* Other Candidates */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich<ref>Chrysene Sigma Aldrich http://www.sigmaaldrich.com/catalog/product/aldrich/245186?lang=en&region=GB</ref> and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png|here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T11:10:26Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

==Other Candidates==
Another molecule that the epoxidation of could be investigated is Chrysene. This is available from Sigma Aldrich and the epoxidation route can be seen [[Media:OJA_Chrysene_Candidate.png||here]]. This would be an interesting investigation due to the conjugation of the system and selectivity required to epoxidise the double bond. The Jacobsen catalyst would be the most sensible choice due to its selective use for cis-alkenes although a modified version may have to be used due to the size of the molecule. More selectivity may be required due to the quantity of bonds available to react and this may also require a modified version of the Jacobsen catalyst.

=References=
<references/>

File:OJA Chrysene Candidate.png

2013-11-22T11:04:51Z

Oa1811: uploaded a new version of "File:OJA Chrysene Candidate.png"

File:OJA Chrysene Candidate.png

2013-11-22T11:04:50Z

Oa1811:

Rep:Mod:OJA692728

2013-11-22T10:50:18Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in Table 1. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''' SOIs in CPD dimerisation]]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in Figure 1 this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in Table 2.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in Table 3.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in Table 4 as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in Tables 5 & 6, and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in Figure 2 along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''Figure 2''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in Table 7. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

{| class="wikitable" border="1"
|+ Table 7
! Bond !! Length (Â)
|-
| C21-C33 || 5.484
|-
| C23-C35 || 3.696
|-
| C24-C34 || 7.606
|-
| C22-C36 || 3.861
|}

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in Tables 8 & 9 below.

{| class="wikitable" border="1"
|+ Table 8: <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ Table 9: <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in Tables 10 & 11 below.

{| class="wikitable" border="1"
|+ Table 10: <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ Table 11: <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ Table 12
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown in Table 12. The energies of all of the trnasition states and the resulting K values can be found in Table 13. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in Figure 3, the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|left|'''Figure 3'''Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
|+ Table 13
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
|+ Table 14
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ Table 15
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above in Table 15 and all the energies of the potential transition states can be seen in Table 16 below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in Figure 4.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|'''Figure 4'''Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
|+ Table 16
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
|+ Table 17
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T10:18:32Z

Oa1811: /* NCI & QTAIM */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in '''TABLEX'''. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and [[Media:OJA_QTAIM_Styrene_R4.png|QTAIM]] analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom200</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T10:17:18Z

Oa1811: /* Styrene Oxide */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in '''TABLEX'''. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T10:16:47Z

Oa1811: /* Spectroscopic Simulation using Quantum Mechanics */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.

As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in '''TABLEX'''. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T10:15:33Z

Oa1811: /* Catalysts */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured however all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in '''TABLEX'''. The planar ring structure of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsion. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryl rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>.

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T10:11:58Z

Oa1811: /* Catalysts */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]

In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px|left]]
To the left is the crystal structure of the Jacobsen catalyst found using Conquest-Mercury. It has an interesting structure as the <sup>t</sup>Bu groups on the outer rings appear to be in close proximity and unfavourable steric interactions are expected between such bulky groups. When measured all of the H-H bond distances were greater than 2Â indicating attractive interactions between them as below 2.1Â the interactions become repulsive. The C-C bond distances are all above 3.6Â and are tabulated in '''TABLEX'''. The planar ring sturcutre of the molecule causes the <sup>t</sup>Bu groups to be far enough apart to not cause steric repulsiions. This will aid the selectivity of the catalyst as the steric bulk of having <sup>t</sup>Bu groups on the aryll rings results in a very crowded Mn centre. This is essential for the Jacobsen catalyst to be able to react selectivty to give >90% ee when epoxidising an alkene<ref>The Mechanistic Basis for Electronic Effects on Enantioselectivity in the (salen)Mn(III)-Catalyzed Epoxidation Reaction ''Michael Palucki, Nathaniel S. Finney, Paul J. Pospisil, Mehmet L. Gu1ler, Toyohisa Ishida, and Eric N. Jacobsen'' {{DOI|10.1021/ja973468j}}</ref>

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-22T09:53:54Z

Oa1811: /* Catalysts */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px|left]]
On the left the crystal structure of the Shi catalyst can be seen. Using Conquest-Mercury the C-O bond lengths of the anomeric centres were measured with interesting results. There were slight differences in the bond lengths both with the anomeric ring and between the two of them. These lengths have been displayed in '''FIGUREX''' along with an optimised 2,2-Dimethyl-1,3-dioxolan to compare them to. Where both carbons are attached to the molecule it shall be referenced as A2 and where only on carbon is attached shall be referenced as A1. [[File:OJA_Anormeric_Shi.png|thumb|500px|right|'''FIGUREX''' C-O bond lengths in the Shi Catalyst]]
In A1 the ring structure is distorted due to it being fused to the central 6 membered ring leading to a lack of flexibility. The C-O bond closest to the carbonyl has a shorter bond length potentially down to favourable interactions of the two oxygen molecules. In A1 the C-O where the carbon is connected to the ring is significantly shorter than expected due to the close proximity of the cyclic oxygen on the other side of it causing the bond to contract. To compensate for this added strain on the 5 membered ring the adjacent C-O bond is close to the expected value.

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

File:OJA Anormeric Shi.png

2013-11-22T09:53:16Z

Oa1811: uploaded a new version of "File:OJA Anormeric Shi.png"

File:OJA Anormeric Shi.png

2013-11-22T09:53:16Z

Oa1811: uploaded a new version of "File:OJA Anormeric Shi.png"

File:OJA Anormeric Shi.png

2013-11-22T09:53:15Z

Oa1811:

Rep:Mod:OJA692728

2013-11-21T20:42:47Z

Oa1811: /* Transition State Analysis */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|600px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|400px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:40:51Z

Oa1811: /* The Hydrogenation of Cyclopentadiene Dimer */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> and <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile> with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

<jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> and <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>, the two hydrogenation products of the CPD dimer, were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:36:47Z

Oa1811: /* NMR */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStyrene> Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref name=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:34:18Z

Oa1811: /* NMR */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref nsme=NMRStyrene>Olivia Ashton ''D-Space'' {{DOI|10042/26247}} </ref> δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStyrene /> δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated<ref nsme=NMRStilbene>Olivia Ashton ''D-Space'' {{DOI|10042/26248}} </ref> δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated<ref name=NMRStilbene /> δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:30:30Z

Oa1811: /* Atropisomerism */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> The first thermally-induced retro-oxy-cope rearrangement ''Steven W. Elmore1, Leo A. Paquette'' {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:28:45Z

Oa1811: /* Atropisomerism */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>Evaluation and prediction of the stability of bridgehead olefins ''Wilhelm F. Maier , Paul Von Rague Schleyer''
{{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:25:26Z

Oa1811: /* Spectroscopic Simulation using Quantum Mechanics */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Olivia Ashton ''D-Space'' {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR>[3.3] Sigmatropy within 1-vinyl-2-alkenyl-7,7-dimethyl-exo-norbornan-2-ols. The first atropselective oxyanionic Cope rearrangement ''Leo A. Paquette , Neil A. Pegg , Dana Toops ,George D. Maynard , Robin D. Rogers''{{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:23:41Z

Oa1811: /* Styrene Oxide */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26246}}</ref>. These are in line with literature values found for λ=589 at -33.3<ref> Stereochemistry and Mechanism of the Photochemical and Thermal Insertion of Oxygen into the Carbon-Cobalt Bond of Alkyl(pyridine)cobaloximes ''Frederick R. Jensen and Ronald C. Kiskis'' {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:20:16Z

Oa1811: /* trans-Stilbene Oxide */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated<ref>Olivia Ashton ''D-Space'' {{DOI|10042/26397}} </ref> and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>
A Diacetate Ketone-Catalyzed Asymmetric Epoxidation of Olefins ''Bin Wang, Xin-Yan Wu, O. Andrea Wong, Brian Nettles, Mei-Xin Zhao, Dajun Chen, and Yian Shi'' {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:16:28Z

Oa1811: /* Shi Epoxidation of Styrene */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>Exploring Substrate Scope of Shi-Type Epoxidations ''Natalia Nietoa, Ian J. Munslowa, Héctor Fernández-Péreza, Anton Vidal-Ferran'' {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal> Exploring structural effects of ketone catalysts on asymmetric epoxidation of olefins ''Zackary Crane,
David Goeddel, Yonghong Gan,Yian Shi'' {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:14:00Z

Oa1811: /* Shi Epoxidation of Styrene */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>
An Efficient Catalyst for Asymmetric Epoxidation of Terminal Olefins

''James P. Collman, Zhong Wang, Andrei Straumanis, and Me ́lanie Quelquejeu'' {{DOI|10.1021/ja9818699}}</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:11:21Z

Oa1811: /* Jacobsen Epoxidation of cis-B-methyl Styrene */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal>Highly Enantioselective Epoxidation Catalysts Derived from 1,2-Diaminocy~lohexane''Eric N. Jacobsen, Wei Zhang, Alexander R. Muci, James R. Ecker, and Li Deng'' {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T20:06:48Z

Oa1811: /* Catalysts */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==
[[File:OJA_Shi_Cat-tiff.png|500px]]

[[File:OJA_Jacob_Cat-tiff.png|500px]]

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

File:OJA Jacob Cat-tiff.png

2013-11-21T20:03:30Z

Oa1811:

File:OJA Shi Cat-tiff.png

2013-11-21T20:03:29Z

Oa1811:

Rep:Mod:OJA692728

2013-11-21T19:51:13Z

Oa1811: /* NCI & QTAIM */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

The 4th (R)-Styrene epoxide transition state has been the focus of NCI and QTAIM analysis. From these the interactions between styrene and the Shi catalyst can be reviewed and maybe help to determine why this is not the lowest energy transition state and hence why (R) Styrene epoxide is the minor product.

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T19:17:51Z

Oa1811: /* Spectroscopic Simulation using Quantum Mechanics */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> {{DOI|10.1021/ja00157a043}}</ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T19:16:54Z

Oa1811: /* Spectroscopic Simulation using Quantum Mechanics */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> <ref>{{DOI|10.1021/ja00157a043}} </ref> δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) !! Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T19:16:15Z

Oa1811: /* The Hydrogenation of Cyclopentadiene Dimer */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> <ref>{{DOI|10.1021/ja00157a043}}</ref>δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T19:15:45Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}
<jmolFile text="Explanatory text for link">BCl3-09.log</jmolFile>
{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule; looking along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

By using the MMFF94s forcefield the energies of <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> and <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile> can be calculated in order to determine which is the more stable conformer. The C6 ring in Molecule 9 was modelled as a twist boat and in Molecule 10 as a chair to be in line with the findings in the literature<ref name=paquette> {{DOI|10.1016/S0040-4039(00)92617-0}} </ref>. It can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4''' as it is ~8 kcal/mol lower in energy than Molecule 9. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette<ref name=paquette /> are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the conformation of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. In molecule 9 the carbonyl group is forced into the same plane as the bridging iso propyl group leading to a larger torsional energy deviation as well as angle bending. Whereas in molecule 10 the carbonyl and bridging group are in opposite planes relieving this strain and hence there is a smaller deviation from the ideal.

In both of these compounds the alkene reacts unusually slowly considering the ring strain and reactivity of the double bond. However this can be put down to the molecules being hyper-stable, where the parent alkane is higher in energy than the corresponding alkene. This phenomena has been observed in molecules where a double bond lies adjacent to a bridgehead but as of yet there is not enough evidence to provide an explanation for why this happens. Maier and Schleyer<ref>http://pubs.acs.org/doi/abs/10.1021/ja00398a003 {{DOI|10.1021/ja00398a003}}</ref> have observed hyper-stability in different cyclic alkenes with differing bridgehead sizes.

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

Using Gaussian an Optmisation and Frequency calculation<ref> Dspace {{DOI|10042/26174}}</ref> was carried out on <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile> in order to establish its NMR Spectrum. The calculated and literature data has been tabulated in '''TABLES5&6''', and a link to the calculated spectra for both <sup>1</sup>H and <sup>13</sup>C are attached to the tables.

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17 [[Media:OJA_Taxol17_NMR.svg]]
! Computed δ (ppm) !! Integration !! Literature<ref name=NMR> <ref>{{DOI|10.1021/ja00157a043}}</ref>δ (ppm) !! Integration

|-
| 5.21 || 1 || 4.84 || 1
|-
| 3.04 || 1 || 3.40-3.10 || 4
|-
| 2.93 || 1 || 2.99 || 1
|-
| 2.82 || 3 || 2.80-1.35 || 14
|-
| 2.76 || 1 || 1.38 || 3
|-
| 2.58 || 1 || 1.25 || 3
|-
| 2.52 || 1 || 1.10 || 3
|-
| 2.30 || 1 || 1.00-0.8 || 1
|-
| 2.11 || 1 || ||
|-
| 1.87 || 3 || ||
|-
| 1.63 || 1 || ||
|-
| 1.47 || 3 || ||
|-
| 1.39 || 1 || ||

|-
| 1.30 || 2 || ||
|-
| 1.12 || 1 || ||

|-
| 0.88 || 1 || ||
|-
| 0.81 || 1 || ||
|-
| 0.74 || 1 || ||
|-
| 0.57 || 2 || ||
|-
| 0.49 || 1 || ||
|-
| 0.30 || 2 || ||

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17 [[Media:OJA_Taxol17_NMR_13C.svg]]
! Computed δ (ppm) Literature<ref name=NMR /> δ (ppm)
|-
| 211.99 || 218.79
|-
| 160.64 || 144.63
|-
| 118.92 || 125.33
|-
| 94.75 || 72.88
|-
| 70.06 || 56.19
|-
| 64.04 || 52.52
|-
| 55.82 || 48.50
|-
| 49.94 || 46.80
|-
| 48.34 || 45.76
|-
| 45.67 || 39.80
|-
| 43.62 || 38.81
|-
| 42.73 || 35.85
|-
| 40.02 || 32.66
|-
| 34.89 || 28.79
|-
| 34.36 || 28.29
|-
| 33.94 || 26.88
|-
| 27.80 || 25.66
|-
| 24.50 || 23.86
|-
| 23.69 || 20.96
|-
| 21.70 || 18.71
|}

It is important to note in the calculated NMR that where the integration is 3 this does not mean a triplet exists, rather that the 3 H's are in very similar chemical environments so their chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39ppm, lit: 1.10-1.38ppm) although the range of values is very different. The two are difficult to compare due to the frequency at which the NMRs have been carried out at. The literature values are determined at 400MHZ whereas the computed spectra it as an undetermined frequency. The discrepancy between these can be part of the reason for slightly different δ values for the same Hydrogens/carbons.
As the literature findings do not specify which shift relates to which atom it is difficult to determine if the spectra has been correctly assigned. As the two have similar ranges and follow the same general pattern it can be concluded that Molecule 17 was made experimentally. The lack of multiplets etc causes the computed NMR data to appear very different to the literature values but on inspection it is seen that the 14H multiplet is merely split out into singlets in the computed version as there is no coupling observed. The literature includes through space interactions which have not been calculated so the extensive coupling seen in the literature is not reflected in the computed data. As there is a general overlap of the two sets of data computing the coupling interactions is not necessary but if for example there was more discrepancy between the two spectra it could be employed to evaluate the literature assignments.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T17:40:04Z

Oa1811:

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}
<jmolFile text="Explanatory text for link">BCl3-09.log</jmolFile>
{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmolFile text="Molecule 1">OJA_Mol1_Energy.cml</jmolFile> || <jmolFile text="Molecule 2">OJA_Mol2_Energy.cml</jmolFile>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmolFile text="Molecule 3">OJA_Mol3_Energy.cml</jmolFile> || <jmolFile text="Molecule 4">OJA_Mol4_Energy.cml</jmolFile>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule. By observing the Newman projections, '''FIGURE2''' along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

OBJECTIVE:WHICH IS THE MOST STABLE

By using the MMFF94s forcefield the energies of molecules 9 and 10 can be calculation in order to determine which is the more stable conformer. By using the conformers that Paquette [ref, doi 10.1016/S0040-4039(00)92617-0) uses in his literature (REF), (molecule 9 C6 ring in a twist boat, molecule 10 C6 ring in a chair) it can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4'''. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the confomration of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. WHAT DOES THE CARBONYL DO?!

Both of these species react slowly when functionalising the alkene which is due to the positioning of the bridging group being adjacent to the double bond. This induces hyper-stability where the alkene is more stable than the parent alkane. In order to assess this phenomena the energy of the the parent alkanes of both 9 and 10 were calculated to give the Olefin Strain (OS) as defined by Maier and Schleyer (ref). Molecule 9 (OS) = Mol10 = 160.77764 Mol 9 = 174.52621

TALK TO ALEX ABOUT HYPERSTABILITY.
{| class="wikitable" border="1"
|+ Jmol Files
! Molecule 9 !! Molecul 10
|-
| <jmolFile text="Molecule 9">OJA_Mol9_Energy.cml</jmolFile> || <jmolFile text="Molecule 10">OJA_Mol10_Energy.cml</jmolFile>

|}

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

{| class="wikitable floatright" border="1"
|+ Molecule 17
| <jmolFile text="Molecule 17">OJA_Taxol_17_Opt.mol</jmolFile>
|}

Using Gaussian an Optmisation and Frequency calculation was carried out on molecule 17 in order to establish its NMR Spectrum. The D-space link for this calculation can be found here: {{DOI|10042/26174}}. The spectra and tabulated proton snd <Sup>13</sup>C NMR data can be found in '''TABLES5&6'''. The literature values that it shall be compared to are as follows: <sup>1</sup>HNMR(300MHz,CDCl<sub>3</sub>):δ 4.84(dd, J=7.2, 4.7Hz, 1H), 3.40-3.10(m, 4H), 2.99(dd, J=6.8, 5.2 Hz, 1H), 2.80-1.35 (series of m, 14H), 1.38 (s, 3H), 1.25 (s, 3H), 1.10(s, 3H), 1.00-0.80(m, 1H)

<sup>13</sup>CNMR(75MHz,CDCl<sub>3</sub>):δ 218.79, 144.63, 125.33, 72.88, 56.19, 52.52,48.50, 46.80, 45.76, 39.80, 38.81, 35.85, 32.66, 28.79, 28.29, 26.88, 25.66, 23.86, 20.96, 18.71 <ref>{{DOI|10.1021/ja00157a043}}</ref>

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 5.21 || 1 || 18 || rowspan="21"|[[File:OJA_Taxol17_NMR.svg|600px]]
|-
| 3.04 || 1 || 28
|-
| 2.93 || 1 || 53
|-
| 2.82 || 3 || 29,34, 52
|-
| 2.76 || 1 || 50
|-
| 2.58 || 1 || 21
|-
| 2.52 || 1 || 51
|-
| 2.30 || 1 || 30
|-
| 2.11 || 1 || 32
|-
| 1.87 || 3 || 22,23,33
|-
| 1.63 || 1 || 31
|-
| 1.47 || 3 || 24, 26, 36
|-
| 1.39 || 1 || 44

|-
| 1.30 || 2 || 35, 25
|-
| 1.12 || 1 || 37

|-
| 0.88 || 1 || 40
|-
| 0.81 || 1 || 27
|-
| 0.74 || 1 || 43
|-
| 0.57 || 2 || 42, 38
|-
| 0.49 || 1 || 41
|-
| 0.30 || 2 || 45, 39

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 211.99 || 1 || 8 || rowspan="20"|[[File:OJA_Taxol17_NMR_13C.svg|600px]]
|-
| 160.64 || 1 || 12

|-
| 118.92 || 1 || 11
|-
| 94.75 || 1 || 3
|-
| 70.06 || 1 || 2
|-
| 64.04 || 1 || 1
|-
| 55.82 || 1 || 15
|-
| 49.94 || 1 || 10
|-
| 48.34 || 1 || 49
|-
| 45.67 || 1 || 48
|-
| 43.62 || 1 || 7
|-
| 42.73 || 1 || 4
|-
| 40.02 || 1 || 9
|-
| 34.89 || 1 || 20
|-
| 34.36 || 1 || 6
|-
| 33.94 || 1 || 13
|-
| 27.80 || 1 || 14
|-
| 24.50 || 1 || 17
|-
| 23.69 || 1 || 5
|-
| 21.70 || 1 || 16

|}
Compare to literature values - no coupling on calulated NMr, same number of peaks in carbon, different in hydrogen, multiplet seen as explicit hydrongens. the program groups them toghtehr, so no triplets shown, in the same range as in paper experimental one not great, relatively old therefore could be run again on more advanced eqipmnt to give a better spectrum?

It is important to note in the calculated NMR that where the degeneracy is 3 Hydrogens this does not mean a triplet exists, rather that the chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39, lit: 1.10-1.38) although the range of values are very different. The two sets of data are difficult to compare as the calculated set does not include coupling and the literature values also include through space interactions which have not been taken into consideration in the calculated set. The calculated set follows the general trend and expectations of the proton NMR, e.g where the hydrogen is next to the double bond or oxygen it is shielded and so left shifted. THe literature values are not assigned to the individual atoms leaving it difficult to understand which hydrogens are interacting and where these signals arise from. It could be speculated that the shift at 4.84ppm is atom 18, the hydrogen attached to the double bond. Other than this one the others could be any of the hydrogens.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR_13C.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}
[[Media:OJA_Styrene_Epoxide_NMR.svg]]
Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Another way to check the integrity of what has been predicted is to use the Optical Rotation Dispersion (ORD) and compare the computational values with the literature. For Styrene oxide the ORD(λ=589nm) was -30.15 and ORD(λ=365nm) was -94.17. These are in line with literature values found for λ=589 at -33.3<ref>http://pubs.acs.org/doi/pdf/10.1021/ja00853a029 {{DOI|10.1021/ja00853a029}} </ref>. These values being close is another indicator that the predicated product matches that widely found in the literature.

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR.svg]]

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}
[[Media:OJA_Stilbene_Epoxide_NMR_13C.svg]]

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

The ORD for trans-Stilbene Oxide have also been calculated and found to be ORD(λ=589) 298.28 and ORD(λ=365) 1255.20. Although there is a larger difference between these values and the literature of ORD(λ=589) 319.8 <ref>http://pubs.acs.org/doi/pdf/10.1021/jo900330n {{DOI|10.1021/jo900330n}} </ref> in comparison to that of Styrene oxide it is still within an acceptable range to confirm that the epoxide being used computationally matches the one found in literature.

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

File:OJA Stilbene Epoxide NMR.svg

2013-11-21T17:36:11Z

Oa1811:

File:OJA Stilbene Epoxide NMR 13C.svg

2013-11-21T17:36:10Z

Oa1811:

File:OJA Styrene Epoxide NMR.svg

2013-11-21T17:36:10Z

Oa1811:

File:OJA Styrene Epoxide NMR 13C.svg

2013-11-21T17:36:09Z

Oa1811:

Rep:Mod:OJA692728

2013-11-21T17:01:52Z

Oa1811: /* NMR */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmol><jmolApplet><title>Molecule 1</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script> <uploadedFileContents>OJA_Mol1_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 2</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol2_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmol><jmolApplet><title>Molecule 3</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol3_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 4</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol4_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule. By observing the Newman projections, '''FIGURE2''' along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

OBJECTIVE:WHICH IS THE MOST STABLE

By using the MMFF94s forcefield the energies of molecules 9 and 10 can be calculation in order to determine which is the more stable conformer. By using the conformers that Paquette [ref, doi 10.1016/S0040-4039(00)92617-0) uses in his literature (REF), (molecule 9 C6 ring in a twist boat, molecule 10 C6 ring in a chair) it can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4'''. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the confomration of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. WHAT DOES THE CARBONYL DO?!

Both of these species react slowly when functionalising the alkene which is due to the positioning of the bridging group being adjacent to the double bond. This induces hyper-stability where the alkene is more stable than the parent alkane. In order to assess this phenomena the energy of the the parent alkanes of both 9 and 10 were calculated to give the Olefin Strain (OS) as defined by Maier and Schleyer (ref). Molecule 9 (OS) = Mol10 = 160.77764 Mol 9 = 174.52621

TALK TO ALEX ABOUT HYPERSTABILITY.
{| class="wikitable" border="1"
|+ Jmol Files
! Molecule 9 !! Molecul 10
|-
| <jmol><jmolApplet><title>Molecule 9</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol9_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 10</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol10_Energy.cml</uploadedFileContents> </jmolApplet></jmol>

|}

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

{| class="wikitable floatright" border="1"
|+ Molecule 17
| <jmol><jmolApplet><title>Molecule 17</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Taxol_17_Opt.mol</uploadedFileContents> </jmolApplet></jmol>
|}

Using Gaussian an Optmisation and Frequency calculation was carried out on molecule 17 in order to establish its NMR Spectrum. The D-space link for this calculation can be found here: {{DOI|10042/26174}}. The spectra and tabulated proton snd <Sup>13</sup>C NMR data can be found in '''TABLES5&6'''. The literature values that it shall be compared to are as follows: <sup>1</sup>HNMR(300MHz,CDCl<sub>3</sub>):δ 4.84(dd, J=7.2, 4.7Hz, 1H), 3.40-3.10(m, 4H), 2.99(dd, J=6.8, 5.2 Hz, 1H), 2.80-1.35 (series of m, 14H), 1.38 (s, 3H), 1.25 (s, 3H), 1.10(s, 3H), 1.00-0.80(m, 1H)

<sup>13</sup>CNMR(75MHz,CDCl<sub>3</sub>):δ 218.79, 144.63, 125.33, 72.88, 56.19, 52.52,48.50, 46.80, 45.76, 39.80, 38.81, 35.85, 32.66, 28.79, 28.29, 26.88, 25.66, 23.86, 20.96, 18.71 <ref>{{DOI|10.1021/ja00157a043}}</ref>

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 5.21 || 1 || 18 || rowspan="21"|[[File:OJA_Taxol17_NMR.svg|600px]]
|-
| 3.04 || 1 || 28
|-
| 2.93 || 1 || 53
|-
| 2.82 || 3 || 29,34, 52
|-
| 2.76 || 1 || 50
|-
| 2.58 || 1 || 21
|-
| 2.52 || 1 || 51
|-
| 2.30 || 1 || 30
|-
| 2.11 || 1 || 32
|-
| 1.87 || 3 || 22,23,33
|-
| 1.63 || 1 || 31
|-
| 1.47 || 3 || 24, 26, 36
|-
| 1.39 || 1 || 44

|-
| 1.30 || 2 || 35, 25
|-
| 1.12 || 1 || 37

|-
| 0.88 || 1 || 40
|-
| 0.81 || 1 || 27
|-
| 0.74 || 1 || 43
|-
| 0.57 || 2 || 42, 38
|-
| 0.49 || 1 || 41
|-
| 0.30 || 2 || 45, 39

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 211.99 || 1 || 8 || rowspan="20"|[[File:OJA_Taxol17_NMR_13C.svg|600px]]
|-
| 160.64 || 1 || 12

|-
| 118.92 || 1 || 11
|-
| 94.75 || 1 || 3
|-
| 70.06 || 1 || 2
|-
| 64.04 || 1 || 1
|-
| 55.82 || 1 || 15
|-
| 49.94 || 1 || 10
|-
| 48.34 || 1 || 49
|-
| 45.67 || 1 || 48
|-
| 43.62 || 1 || 7
|-
| 42.73 || 1 || 4
|-
| 40.02 || 1 || 9
|-
| 34.89 || 1 || 20
|-
| 34.36 || 1 || 6
|-
| 33.94 || 1 || 13
|-
| 27.80 || 1 || 14
|-
| 24.50 || 1 || 17
|-
| 23.69 || 1 || 5
|-
| 21.70 || 1 || 16

|}
Compare to literature values - no coupling on calulated NMr, same number of peaks in carbon, different in hydrogen, multiplet seen as explicit hydrongens. the program groups them toghtehr, so no triplets shown, in the same range as in paper experimental one not great, relatively old therefore could be run again on more advanced eqipmnt to give a better spectrum?

It is important to note in the calculated NMR that where the degeneracy is 3 Hydrogens this does not mean a triplet exists, rather that the chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39, lit: 1.10-1.38) although the range of values are very different. The two sets of data are difficult to compare as the calculated set does not include coupling and the literature values also include through space interactions which have not been taken into consideration in the calculated set. The calculated set follows the general trend and expectations of the proton NMR, e.g where the hydrogen is next to the double bond or oxygen it is shielded and so left shifted. THe literature values are not assigned to the individual atoms leaving it difficult to understand which hydrogens are interacting and where these signals arise from. It could be speculated that the shift at 4.84ppm is atom 18, the hydrogen attached to the double bond. Other than this one the others could be any of the hydrogens.

=Part 2=

==Catalysts==

==NMR==

===Styrene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for Styrene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}

Due to the sensitivity that the shifts can be reported to using computational methods, where in experimental cases the atoms are seen as being in the same environment they can sometimes be recorded individually. However on the whole a general match can be seen between the computational and literature assignments leading to confidence in the optmised Styrene Epoxide.

Optical rotation link http://pubs.acs.org/doi/pdf/10.1021/ja00853a029

===trans-Stilbene Oxide===

The computed <sup>1</sup>H and <sup>13</sup>C NMR and the related literature finidings for trans-Stilbene oxide have been tabluated in '''TABLEX&X''' below.

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}

As with Styrene Oxide there are issues surrounding the quantity of peaks collected by NMR analysis but again this can be put down to the sensitivity of the computational method vs the experimental machines. A general fit is seen again with this data and shifts are in the expected range of ppm for the molecule.

optical rotation link http://pubs.acs.org/doi/pdf/10.1021/jo900330n

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T16:37:15Z

Oa1811: /* Jacobsen Epoxidation of cis-B-methyl Styrene */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmol><jmolApplet><title>Molecule 1</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script> <uploadedFileContents>OJA_Mol1_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 2</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol2_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmol><jmolApplet><title>Molecule 3</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol3_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 4</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol4_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule. By observing the Newman projections, '''FIGURE2''' along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

OBJECTIVE:WHICH IS THE MOST STABLE

By using the MMFF94s forcefield the energies of molecules 9 and 10 can be calculation in order to determine which is the more stable conformer. By using the conformers that Paquette [ref, doi 10.1016/S0040-4039(00)92617-0) uses in his literature (REF), (molecule 9 C6 ring in a twist boat, molecule 10 C6 ring in a chair) it can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4'''. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the confomration of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. WHAT DOES THE CARBONYL DO?!

Both of these species react slowly when functionalising the alkene which is due to the positioning of the bridging group being adjacent to the double bond. This induces hyper-stability where the alkene is more stable than the parent alkane. In order to assess this phenomena the energy of the the parent alkanes of both 9 and 10 were calculated to give the Olefin Strain (OS) as defined by Maier and Schleyer (ref). Molecule 9 (OS) = Mol10 = 160.77764 Mol 9 = 174.52621

TALK TO ALEX ABOUT HYPERSTABILITY.
{| class="wikitable" border="1"
|+ Jmol Files
! Molecule 9 !! Molecul 10
|-
| <jmol><jmolApplet><title>Molecule 9</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol9_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 10</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol10_Energy.cml</uploadedFileContents> </jmolApplet></jmol>

|}

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

{| class="wikitable floatright" border="1"
|+ Molecule 17
| <jmol><jmolApplet><title>Molecule 17</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Taxol_17_Opt.mol</uploadedFileContents> </jmolApplet></jmol>
|}

Using Gaussian an Optmisation and Frequency calculation was carried out on molecule 17 in order to establish its NMR Spectrum. The D-space link for this calculation can be found here: {{DOI|10042/26174}}. The spectra and tabulated proton snd <Sup>13</sup>C NMR data can be found in '''TABLES5&6'''. The literature values that it shall be compared to are as follows: <sup>1</sup>HNMR(300MHz,CDCl<sub>3</sub>):δ 4.84(dd, J=7.2, 4.7Hz, 1H), 3.40-3.10(m, 4H), 2.99(dd, J=6.8, 5.2 Hz, 1H), 2.80-1.35 (series of m, 14H), 1.38 (s, 3H), 1.25 (s, 3H), 1.10(s, 3H), 1.00-0.80(m, 1H)

<sup>13</sup>CNMR(75MHz,CDCl<sub>3</sub>):δ 218.79, 144.63, 125.33, 72.88, 56.19, 52.52,48.50, 46.80, 45.76, 39.80, 38.81, 35.85, 32.66, 28.79, 28.29, 26.88, 25.66, 23.86, 20.96, 18.71 <ref>{{DOI|10.1021/ja00157a043}}</ref>

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 5.21 || 1 || 18 || rowspan="21"|[[File:OJA_Taxol17_NMR.svg|600px]]
|-
| 3.04 || 1 || 28
|-
| 2.93 || 1 || 53
|-
| 2.82 || 3 || 29,34, 52
|-
| 2.76 || 1 || 50
|-
| 2.58 || 1 || 21
|-
| 2.52 || 1 || 51
|-
| 2.30 || 1 || 30
|-
| 2.11 || 1 || 32
|-
| 1.87 || 3 || 22,23,33
|-
| 1.63 || 1 || 31
|-
| 1.47 || 3 || 24, 26, 36
|-
| 1.39 || 1 || 44

|-
| 1.30 || 2 || 35, 25
|-
| 1.12 || 1 || 37

|-
| 0.88 || 1 || 40
|-
| 0.81 || 1 || 27
|-
| 0.74 || 1 || 43
|-
| 0.57 || 2 || 42, 38
|-
| 0.49 || 1 || 41
|-
| 0.30 || 2 || 45, 39

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 211.99 || 1 || 8 || rowspan="20"|[[File:OJA_Taxol17_NMR_13C.svg|600px]]
|-
| 160.64 || 1 || 12

|-
| 118.92 || 1 || 11
|-
| 94.75 || 1 || 3
|-
| 70.06 || 1 || 2
|-
| 64.04 || 1 || 1
|-
| 55.82 || 1 || 15
|-
| 49.94 || 1 || 10
|-
| 48.34 || 1 || 49
|-
| 45.67 || 1 || 48
|-
| 43.62 || 1 || 7
|-
| 42.73 || 1 || 4
|-
| 40.02 || 1 || 9
|-
| 34.89 || 1 || 20
|-
| 34.36 || 1 || 6
|-
| 33.94 || 1 || 13
|-
| 27.80 || 1 || 14
|-
| 24.50 || 1 || 17
|-
| 23.69 || 1 || 5
|-
| 21.70 || 1 || 16

|}
Compare to literature values - no coupling on calulated NMr, same number of peaks in carbon, different in hydrogen, multiplet seen as explicit hydrongens. the program groups them toghtehr, so no triplets shown, in the same range as in paper experimental one not great, relatively old therefore could be run again on more advanced eqipmnt to give a better spectrum?

It is important to note in the calculated NMR that where the degeneracy is 3 Hydrogens this does not mean a triplet exists, rather that the chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39, lit: 1.10-1.38) although the range of values are very different. The two sets of data are difficult to compare as the calculated set does not include coupling and the literature values also include through space interactions which have not been taken into consideration in the calculated set. The calculated set follows the general trend and expectations of the proton NMR, e.g where the hydrogen is next to the double bond or oxygen it is shielded and so left shifted. THe literature values are not assigned to the individual atoms leaving it difficult to understand which hydrogens are interacting and where these signals arise from. It could be speculated that the shift at 4.84ppm is atom 18, the hydrogen attached to the double bond. Other than this one the others could be any of the hydrogens.

=Part 2=

==Catalysts==

==NMR==

===Styrene===
Styrene epoxide NMR (1H & 13C) literature: http://www.tandfonline.com/doi/pdf/10.1080/00397911.2010.539755

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}

Optical rotation link http://pubs.acs.org/doi/pdf/10.1021/ja00853a029

===Stilbene===
trans-Stilbene epoxide NMR (1H & 13 C) literature: http://www.sciencedirect.com/science/article/pii/S0040402013007710

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}

optical rotation link http://pubs.acs.org/doi/pdf/10.1021/jo900330n

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />]]

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>

Rep:Mod:OJA692728

2013-11-21T16:36:39Z

Oa1811: /* Transition State Analysis */

=Part 1=
==The Hydrogenation of Cyclopentadiene Dimer==

Using Computational Methods the stability of the kinetic and thermodynamic products of cyclopentadiene (CPD) dimerisation have been calculated. Using Avagadro to optimise both structures 1 and 2 with a MMFF94(s) force field the energies of the compounds has been calculated in kcal/mol and are shown in '''TABLE1'''. From this it can be seen that product 1 is thermodynamically more stable and is lower in energy by ~3 kcal/mol. However, despite being higher in energy, the Kinetic product 2 is the one most observed when this dimerisation takes place. This leads one to assume that the reaction must be controlled by kinetics as opposed to thermodynamics meaning the transition state of the reaction to form 2 is lower in energy than that of 1.

{| class="wikitable" border="1"
|+ Table 1
! Energy !! 1 (Exo) !! 2 (Endo)
|-
| Bond Stretching || 3.54305 || 3.46800
|-
| Angle Bending || 30.77276 || 33.18902
|-
| Torsional || -2.73088 || -2.94965
|-
| van der Waals || 12.80147 || 12.35890
|-
| Electrostatic || 13.01367 || 14.18474
|-
| '''Total''' || '''55.37342''' || '''58.19067'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol files
! Molecule 1 !! Molecule 2
|-
| <jmol><jmolApplet><title>Molecule 1</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script> <uploadedFileContents>OJA_Mol1_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 2</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol2_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

[[File:OJA_1Exo2Endo_TS_mech.png|thumb|right|200px|'''Figure 1''']]One explanation of this phenomena is the Secondary Orbital Interactions (SOIs) present in the endo (2) transition state which are not in the exo form. From the diagrams in '''FIGURE1''' this interaction can be seen; the mechanistic arrows are in red and the proposed SOIs of the Carbon p<sub>z</sub> orbitals in the endo form are in blue. This added interaction stabilizes the endo transition state as the two orbitals keep the CPD rings in position during the reaction and the part combination of the orbitals contributes to the lowering of energy for the entire system.

However there is another theory to explain the favoring of the endo product and hence why the reaction is kinetically controlled. By analyzing the endo and exo transition state and interesting feature regarding the individual stabilities of the Carbons and Hydrogens has been unearthed. <ref name = WerstiukSokol> QTAIM-DI-VISAB computational study on the Diels-Alder reaction of cyclopentadiene - On the nature of the so-called secondary orbital interactions, ''N. Werstiuk, W. Sokol'' {{DOI|10.1139/v08-070}} </ref>It can be argued that is the increased stabilisation of the Hydorgen atoms on both CPD rings that leads to a lowering of the energy barrier to form the endo product. As the sp<sup>2</sup> carbons rehybridize to sp<sup>3</sup> charge is transferred from the carbon to the hydrogen thus lowering it in energy. In the endo form the stabilization of the hydrogens is reflected in the second ring whereas in the exo TS this relationship is asymmetric thus leaving it unbalanced and as a whole transition state less stable. The pronunciation of Carbon sp<sup>2</sup> to sp<sup>3</sup> rehybridization is greater in the endo TS leading to a greater charge transfer and thus a greater stabilization. The stabilization energies calculated in this paper can be seen in '''TABLE2'''.

{| class="wikitable" border="1"
|+ Table 2 <ref name= WerstiukSokol />
! rowspan="2"| !! colspan="2"|Endo !! colspan="2"|Exo
|-
| CPD || CPD' || CPD || CPD'
|-
| Σ(ΔE<sub>C</sub>) || 36.73 || 36.73 || 17.03 || 50.34
|-
| Σ(ΔE<sub>H</sub>) || -28.10 || -28.10 || -19.32 || -27.12
|}

The two hydrogenation products of the CPD dimer were also evaluated using a similar method as above in order to establish which product is the result of thermodynamic and/or kinetic control. The results of these calculations can be seen in '''TABLE3'''.

{| class="wikitable" border="1"
|+ Table 3
! Energy !! 3 !! 4
|-
| Bond Stretching || 3.30608 || 2.82311
|-
| Angle Bending || 30.85293 || 24.68536
|-
| Torsional || 0.07367 || -0.37840
|-
| van der Waals || 13.28027 || 10.63731
|-
| Electrostatic || 5.12099 || 5.14702
|-
| '''Total''' || '''50.72279''' || '''41.25749'''
|}

{| class="wikitable floatright" border="1"
|+ Jmol Files
! Molecule 3 !! Molecule 4
|-
| <jmol><jmolApplet><title>Molecule 3</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol3_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 4</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol4_Energy.cml</uploadedFileContents> </jmolApplet></jmol>
|}

It can be concluded that that 4 is the thermodynamic product of the hydrogenation of the CPD dimer as it is lower in energy than 3. From the data in Table 3 it can be seen that both the angle bending and bond stretching energies are greater in molecule 3 which can be put down to the increased ring strain in the six membered ring. It has a bridging methyl group and a double bond which will both but a considerable amount of strain on the ring leading to it deviating from the expected 'norm' more. This in contrast to 4 which has the two limiting features spread across the whole molecule, and this is reflected in the negative torsional energy reported for the molecule. The electrostatic energy is almost the same as the molecules have the same empirical formula and basic structure so no differences in electrostatic energies was predicted. Another interesting feature is the position of the groups alongside the double bond in each molecule. By observing the Newman projections, '''FIGURE2''' along these bonds it can be seen that the hydrogens in 3 are in an eclipsed form whereas in molecule 4 they are gauche. This indicates that 4 is more stable than 3 as there is less steric hinderance between the groups adjacent to the double bonds. All of these factors contribute to 4 being lower in energy and thus the thermodynamic product of the hydrogenation of the CPD dimer.

From the data collected the kinetic product of the reaction can not be determined, as although 4 is the thermodynamic product it can still also be the kinetic product and due to the lack of conclusive data it would be wrong to assign either 3 or 4 as the kinetic product of this reaction.

==Atropisomerism==

OBJECTIVE:WHICH IS THE MOST STABLE

By using the MMFF94s forcefield the energies of molecules 9 and 10 can be calculation in order to determine which is the more stable conformer. By using the conformers that Paquette [ref, doi 10.1016/S0040-4039(00)92617-0) uses in his literature (REF), (molecule 9 C6 ring in a twist boat, molecule 10 C6 ring in a chair) it can be seen that Molecule 10 is the thermodynamically stable of the two by evaluating the Total energies, in '''TABLE4'''. Interestingly when molecule 10 was in the opposite chair form the energy was much higher, at approximately 180kcal/mol. Other configurations of the C6 ring were tried in order to determine if there was one in a lower energy but the ones laid out by Paquette are the lowest forms of both of the molecules although the correct directionality of the ring has to be taken into consideration.

Apart from the configuraiton of the C6 ring the difference in these two molecules is where the carbonyl group points and the confomration of he C6 ring is arguably determined by this positioning as well in order to relieve the added strain. WHAT DOES THE CARBONYL DO?!

Both of these species react slowly when functionalising the alkene which is due to the positioning of the bridging group being adjacent to the double bond. This induces hyper-stability where the alkene is more stable than the parent alkane. In order to assess this phenomena the energy of the the parent alkanes of both 9 and 10 were calculated to give the Olefin Strain (OS) as defined by Maier and Schleyer (ref). Molecule 9 (OS) = Mol10 = 160.77764 Mol 9 = 174.52621

TALK TO ALEX ABOUT HYPERSTABILITY.
{| class="wikitable" border="1"
|+ Jmol Files
! Molecule 9 !! Molecul 10
|-
| <jmol><jmolApplet><title>Molecule 9</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol9_Energy.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>Molecule 10</title><color>white</color> <size>150</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Mol10_Energy.cml</uploadedFileContents> </jmolApplet></jmol>

|}

{| class="wikitable" border="1"
|+ Table 4
! Energy !! Molecule 9 !! Molecule 10
|-
| Bond Stretching || 13.39848 || 12.69138
|-
| Angle Bending || 59.85832 || 53.18714
|-
| Stretch Bending || 0.09336 || -0.58690
|-
| Torsional || 6.92784 || 6.11050
|-
| Out-Of-Plane Bending || 2.20617 || 2.34193
|-
| vsn der Waals || 48.70837 || 48.76756
|-
| Electrostatic || 1.42447 || 1.91772
|-
| Total || 132.61700 || 124.42933
|}

==Spectroscopic Simulation using Quantum Mechanics==

{| class="wikitable floatright" border="1"
|+ Molecule 17
| <jmol><jmolApplet><title>Molecule 17</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Taxol_17_Opt.mol</uploadedFileContents> </jmolApplet></jmol>
|}

Using Gaussian an Optmisation and Frequency calculation was carried out on molecule 17 in order to establish its NMR Spectrum. The D-space link for this calculation can be found here: {{DOI|10042/26174}}. The spectra and tabulated proton snd <Sup>13</sup>C NMR data can be found in '''TABLES5&6'''. The literature values that it shall be compared to are as follows: <sup>1</sup>HNMR(300MHz,CDCl<sub>3</sub>):δ 4.84(dd, J=7.2, 4.7Hz, 1H), 3.40-3.10(m, 4H), 2.99(dd, J=6.8, 5.2 Hz, 1H), 2.80-1.35 (series of m, 14H), 1.38 (s, 3H), 1.25 (s, 3H), 1.10(s, 3H), 1.00-0.80(m, 1H)

<sup>13</sup>CNMR(75MHz,CDCl<sub>3</sub>):δ 218.79, 144.63, 125.33, 72.88, 56.19, 52.52,48.50, 46.80, 45.76, 39.80, 38.81, 35.85, 32.66, 28.79, 28.29, 26.88, 25.66, 23.86, 20.96, 18.71 <ref>{{DOI|10.1021/ja00157a043}}</ref>

{| class="wikitable" border="1"
|+ Table 5: <sup>1</sup>H NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 5.21 || 1 || 18 || rowspan="21"|[[File:OJA_Taxol17_NMR.svg|600px]]
|-
| 3.04 || 1 || 28
|-
| 2.93 || 1 || 53
|-
| 2.82 || 3 || 29,34, 52
|-
| 2.76 || 1 || 50
|-
| 2.58 || 1 || 21
|-
| 2.52 || 1 || 51
|-
| 2.30 || 1 || 30
|-
| 2.11 || 1 || 32
|-
| 1.87 || 3 || 22,23,33
|-
| 1.63 || 1 || 31
|-
| 1.47 || 3 || 24, 26, 36
|-
| 1.39 || 1 || 44

|-
| 1.30 || 2 || 35, 25
|-
| 1.12 || 1 || 37

|-
| 0.88 || 1 || 40
|-
| 0.81 || 1 || 27
|-
| 0.74 || 1 || 43
|-
| 0.57 || 2 || 42, 38
|-
| 0.49 || 1 || 41
|-
| 0.30 || 2 || 45, 39

|}

{| class="wikitable" border="1"
|+ Table 6: <sup>13</sup>C NMR of Taxol-17
! Shift (ppm) !! Degeneracy !! Atom(s) || Spectra
|-
| 211.99 || 1 || 8 || rowspan="20"|[[File:OJA_Taxol17_NMR_13C.svg|600px]]
|-
| 160.64 || 1 || 12

|-
| 118.92 || 1 || 11
|-
| 94.75 || 1 || 3
|-
| 70.06 || 1 || 2
|-
| 64.04 || 1 || 1
|-
| 55.82 || 1 || 15
|-
| 49.94 || 1 || 10
|-
| 48.34 || 1 || 49
|-
| 45.67 || 1 || 48
|-
| 43.62 || 1 || 7
|-
| 42.73 || 1 || 4
|-
| 40.02 || 1 || 9
|-
| 34.89 || 1 || 20
|-
| 34.36 || 1 || 6
|-
| 33.94 || 1 || 13
|-
| 27.80 || 1 || 14
|-
| 24.50 || 1 || 17
|-
| 23.69 || 1 || 5
|-
| 21.70 || 1 || 16

|}
Compare to literature values - no coupling on calulated NMr, same number of peaks in carbon, different in hydrogen, multiplet seen as explicit hydrongens. the program groups them toghtehr, so no triplets shown, in the same range as in paper experimental one not great, relatively old therefore could be run again on more advanced eqipmnt to give a better spectrum?

It is important to note in the calculated NMR that where the degeneracy is 3 Hydrogens this does not mean a triplet exists, rather that the chemical shifts are so close that Gaussian has grouped them together under one signal. The methyl hydrogens are identifiable and comparable with the literature values being at the lower end of the spectrum (cal: 0.30--1.39, lit: 1.10-1.38) although the range of values are very different. The two sets of data are difficult to compare as the calculated set does not include coupling and the literature values also include through space interactions which have not been taken into consideration in the calculated set. The calculated set follows the general trend and expectations of the proton NMR, e.g where the hydrogen is next to the double bond or oxygen it is shielded and so left shifted. THe literature values are not assigned to the individual atoms leaving it difficult to understand which hydrogens are interacting and where these signals arise from. It could be speculated that the shift at 4.84ppm is atom 18, the hydrogen attached to the double bond. Other than this one the others could be any of the hydrogens.

=Part 2=

==Catalysts==

==NMR==

===Styrene===
Styrene epoxide NMR (1H & 13C) literature: http://www.tandfonline.com/doi/pdf/10.1080/00397911.2010.539755

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature<ref name = StyreneNMR>ENVIROCAT (K10-MX)–CATALYZED REGIOSELECTIVE TRANSFORMATION OF ALKENES INTO IODOHYDRINS AND b-IODO ETHERS AND FURTHER CONVERSION OF IODOHYDRINS TO EPOXIDES USING Al2O3-Na2CO3 UNDER MWI ''Shallu, M. L. Sharma, and Jasvinder Singh'' {{DOI|10.1080/00397911.2010.539755}} </ref> δ (ppm)

|-
| 2.5 || 2.79
|-
| 3.1 || 3.13
|-
| 3.7 || 3.85
|-
| 7.3 || 7.33-7.37
|-
| 7.5 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name=StyreneNMR /> δ (ppm)
|-
| 53.5 || 51.3
|-
| 54.1 || 52.4
|-
| 118.3 || 125.5
|-
| 123.0 || 128.2
|-
| 123.4 || 128.8
|-
| 124.1 || 137.6
|-
| 135.1 || -
|}

Optical rotation link http://pubs.acs.org/doi/pdf/10.1021/ja00853a029

===Stilbene===
trans-Stilbene epoxide NMR (1H & 13 C) literature: http://www.sciencedirect.com/science/article/pii/S0040402013007710

{| class="wikitable" border="1"
|+ <sup>1</sup>H NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR> Sequential- and tandem-oxidation–epoxidation reactions employing guanidine bases, ''David J. Phillips,
Joseline L. Kean, Andrew E. Graham'' {{DOI|10.1016/j.tet.2013.05.036}} </ref> δ (ppm)

|-
| 3.5 || 3.95
|-
| 7.5 || 7.40-7.55
|-
| 7.6 || -
|}

{| class="wikitable" border="1"
|+ <sup>13</sup>C NMR
! Calculated δ (ppm) !! Literature <ref name = StilbeneNMR /> δ (ppm)
|-
| 66.4 || 62.7
|-
| 118.3 || 125.5
|-
| 123.1 || 128.2
|-
| 123.2|| 128.5
|-
| 123.5 || 137.1
|-
| 124.2 || -
|-
| 134.1 || -
|}

optical rotation link http://pubs.acs.org/doi/pdf/10.1021/jo900330n

==Transition State Analysis==
===Shi Epoxidation of Styrene===

{| class="wikitable" border="1"
|+ caption
! (R) Styrene Jmol !! (S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(R) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_R_TS_4.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(S) Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_Styrene_S_TS_4.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The lowest energy (R) and (S) Styrene epoxides Jmols are shown above. The energies of all of the trnasition states and the resulting K values can be found in '''TABLEX'''. From the K value calculated the enantiomeric excess (ee) has been calculated as 23.84% in favour of the (S) product which is complimetary of the literature values which range from 11-26% ee for styrene and its derivatives<ref name = Styrene S ee>https://www.thieme-connect.de/DOI/DOI?10.1055/s-0028-1083545 {{DOI|10.1055/s-0028-1083545}} </ref>. At a first look this seems extremely low however it is the lack of substituion on the alkene that leads to such poor selectivity in comparison to tri-subsititued alkenes where the selectivity with the SHi catalyst is often above 90%. Due to the importance of sterics in the spiro transition state when using the Shi catalyst, seen in '''FIGUREX''', the lack of subsitutioent on the terminal alkene in styrene results in poor slectivity for either S or R<ref name=ShiCatalystOriginal>http://www.sciencedirect.com/science/article/pii/S0040402005006022 {{DOI|10.1016/j.tet.2005.03.123.}}</ref>. In order to increase the ee for styrene epoxidation a modified version of the shi catalyst can be used which includes a carbocyclic oxazolidinione containing keotine. , and others for terminal alkenes, it is suggested that a modified version of the Shi catalysed to be used which doesn't rely upon steric effects for selectivity<ref name=ShiCatalystOriginal />. There have been other studeis into the epoxidation of temrinal aleknes and how to increase the selectivity of the reaction to yield great ee's but often these are not based on Fructose or ketone containing compounds<ref>http://pubs.acs.org/doi/pdf/10.1021/ja9818699</ref>.

The (S) epxoide being more stable indicates more favourable interactions between the methyl groups of the catalyst with styrene indicated by the shorted through space distances; (S) TS: 3.78A, (R) TS: 3.92A. Both values indicative attractive interactions (check with NCI of R) but more so for the (S) enantiomer. Interestingly in the (S) TS Styrene retains the majority of its planarity whereas in (R) the terminal alkene is bent up towards the catalyst which could be seen to contribute to the (S) being the more favourable TS for epoxidation as Styrene has not been distorted.

[[File:OJA_Spiro_TS_A-tiff.png|100px|thumb|Spiro Transition State in the Epoxidation of Alkenes using the Shi Catalyst <ref name=ShiCatalystOriginal />]]

{| class="wikitable collapsible"
! colspan="7"| Shi
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| R
| S
| Hartree
| j/mol
|-
| 1
| -1303.730703
| -1303.733828
| align="centre" | 0.003125
| align="centre" | 8204.686312
| align="centre" | -3.309917336
| align="centre" | 0.036519192
|-
| 2
| -1303.730238
| -1303.724178
| align="centre" | -0.006060
| align="centre" | -15910.5277
| align="centre" | 6.418591699
| align="centre" | 613.1390213
|-
| 3
| -1303.736813
| -1303.727673
| align="centre" | -0.009140
| align="centre" | -23997.06653
| align="centre" | 9.680846225
| align="centre" | 16008.0376
|-
| 4
| -1303.738044
| -1303.738503
| align="centre"| 0.000459
| align="centre" | 1205.104326
| align="centre" | -0.486160658
| align="centre" | 0.614982997!
|}

{| class="wikitable" "collapsible autocollapse"
! colspan="4"|ee Calculations

|-
| R
| S
| ee
| ee%
|-
| 0.380798435
| 0.619201565
| 0.238403131
| 23.84
|}

===Jacobsen Epoxidation of cis-B-methyl Styrene===

{| class="wikitable" border="1"
|+ caption
! (S,R) Styrene Jmol !! (R,S) Styrene Jmol
|-
| <jmol><jmolApplet><title>(S,R) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_S,R_TS_1.cml</uploadedFileContents> </jmolApplet></jmol> || <jmol><jmolApplet><title>(R,S) cis-Styrene</title><color>white</color> <size>350</size><script>zoom 5;moveto 4 0 2 0 90 120;spin 2;</script><uploadedFileContents>OJA_cis_Styrene_R,S_TS_1.cml</uploadedFileContents> </jmolApplet></jmol>
|}

The two Lowest energy TS Jmol's can be seen above and all the energies of the potential transition states can be seen in '''TABLEX''' below. As before, the enantiomeric excess was calculated by taking the difference in the Free Energies in order to find K and then using this to get the relative ratios of products. In this case an ee of 99.98% was calculated in favour of the (S,R) product which in the literature has an ee of 92% <ref name=JacobsenCatalystOriginal> http://pubs.acs.org/doi/pdf/10.1021/ja00018a068 {{DOI|10.1021/ja00018a068}} </ref>. The high selectivity of this catalyst with cis-B-methyl styrene is put down to the alkene only being able to approach side on from one direction as seen in '''FIGUREX'''.

[[File:OJA_cisBMeStyrene_TS-tiff.png|100px|thumb|Favourable approach of cis-alkenes to Jacobsen's Catalyst for Epoxidation<ref name=JacobsenCatalystOriginal />

By examining both the (S,R) and (R,S) transition states the idea proposed that the face selectivity is attributed to the position of the phenyl group in relation to the axial hydrogen on the bridge<ref name=JacobsenCatalystOriginal /> holds true. In the (R,S) TS this through space distance is 4.08A where as in the (S,R) TS it is larger at 4.67A indicating that the interaction of these two parts is repulsive causing the (S,R) transition state to be the more stable one.

{| class="wikitable collapsible"
! colspan="7" | Jacobsen
|-
| rowspan="2" | TS
| colspan="2" | Electronic and Thermal Energies
| colspan="2" | ΔG
| rowspan="2" | lnK
| rowspan="2" | K
|-
| S,R
| R,S
| Hartree
| j/mol
|-
| 1
| -3383.259559
| -3383.251060
| align="right" | 0.008499
| align="right" | 22314.12127
| align="right" | -9.001915981
| align="right" | 0.000123174
|-
| 2
| -3383.253442
| -3383.250270
| align="right" | 0.003172
| align="right" | 8328.084795
| align="right" | -3.359698493
| align="right" | 0.034745733!
|}

{| class="wikitable collapsible"
! colspan="4"|ee Calculations
|-
| S,R
| R,S
| ee
| ee %
|-
| 0.999876842
| 0.000123158
| 0.999753683
| 99.98
|}

===NCI & QTAIM===

<jmol> <jmolApplet> <title>Orbital</title><color>white</color><size>300</size> <script>isosurface color orange purple "images/d/da/Styrene_R_series_4_den.cub.jvxl";zoom120</script> <uploadedFileContents>OJA_Styrene_R_series_4_den.cub.xyz</uploadedFileContents> </jmolApplet> </jmol>

[[File:OJA_QTAIM_Styrene_R4.png|400px]]

=References=
<references/>