Rep:Mod:shiyingli

Shiying Li's 1C Report

Part 1

The Hydrogenation of Cyclopentadiene Dimer

Scheme 1:Reaction Scheme for the Dimerisation

In Scheme 1, the cyclopentadiene undergoes dimerization then form two possible dimers which are endo and exo conformations in room temperature. However, experimental result shows that only one of the dimers could exist, just the endo form. To figure why the endo dimer is preferred, two dimers (Molecule 1 and 2 in the scheme) were drawn using ChemDraw and their molecular geometries were optimized by Avogadro.

Table 1: Energy minima after optimizations

Molecules	1 (kcal/mol)	2 (kcal/mol)	3 (kcal/mol)	4 (kcal/mol)
Geometries	Cp-dimer1.mol	Cp-dimer2.mol	Hydrogenated-3.mol	Hydrogenated-4.mol
Total Bond Stretching Energy	3.54301	3.46745	3.31176	2.82306
Total Angle Bending Energy	30.77268	33.19079	31.96288	24.68543
Total Stretch-Bending Energy	-2.04138	-2.08217	-2.10361	-1.65717
Total Torsional Energy	-2.73105	-2.94971	-1.49561	-0.37830
Total Out-of-Plane Bending Energy	0.01485	0.02193	0.01298	0.00028
Total VAN DER WAALS Energy	12.80166	12.353773	13.63776	10.63717
Total Electrostatic Energy	13.01367	14.18466	5.11952	5.14702
Total Energy	55.37344	58.19070	50.44568	41.25749

The energy of the conformer’s maximum was calculated using MMF94s force field and conjugate gradients algorithm. The hydrogenation of the endo form produces two different hydrogenated product that are Molecule 3 and 4. Same optimisations process was applied to molecule 3 and 4 to investigate which hydrogenation is preferred. The results were showed in Table 1. From the table shows above, molecule 4 has a lower energy than the molecule 3. If the hygenation of the dimer is under thermodynamic controlled, the double bond in the norbornene is hydrogenated faster than the double bond in the cylcopentane ring. Besides, the molecules 3 and 4 can be accounted in different energy terms. Besides the total electrostatic energy and total stretch bending energy, the molecule 4 generally has a lower value than molecule 3 in the remained energy contributions. In conclusion, the total angle bending energy and total van der Waals energy are the most contribution towards the lower stability of the molecule 4.

Part 1: Atropisomerism in an Intermediate related to the Synthesis of Taxol

Introduction

Scheme 2:Molecules 9

Scheme 3:Molecules 10

Molecule 9 or 10 are the most important structure of taxol (used in chemotherapy for ovarian cancers) synthesis. They are atropisomers to each other and the main difference is the C=O bond pointing direction, one point up another point down. The energy barrier of bond rotation for these 9 and 10 intermediates enables them to be isolated separately. They both are synthesised from an oxy-Cope rearrangement and their stability was investigated by using Avogadro with the MMFF94(s) force field.

Table 2: Energy minima of Molecule 9 and 10 and their hydrogenated products 9* and 10*

Molecules	9 (kcal/mol)	10 (kcal/mol)	9* (kcal/mol)	10* (kcal/mol)
Geometries	Molecule_9.mol	Molecule_10.mol	Molecule_9-hydrogenated.mol	Molecule_10-hydrogenated.mol
Total Bond Stretching Energy	7.6447	7.58965	7.29234	6.40661
Total Angle Bending Energy	28.24946	18.77878	23.29595	22.30294
Total Stretch-Bending Energy	-0.08815	-0.14633	0.15268	0.29349
Total Torsional Energy	0.33774	0.19473	10.71749	9.27344
Total Out-of-Plane Bending Energy	0.97957	0.84700	0.13196	0.03641
Total VAN DER WAALS Energy	33.12333	33.25936	34.24838	31.23140
Total Electrostatic Energy	0.30327	-0.04868	0.00000	0.00000
Total Energy	70.54924	60.55231	75.83879	69.54428

Table 3:Possible structures of molecule 9 and 10 but with higher energy than optimised one

	molecule 9	molecule 9	molecule 9	molecule 10	molecule 10	molecule 10
Structure	Another Chair form	Slightly twisted boat form	Optimised form but with trans H pointing down	Another Chair form	Slightly twisted boat form	Optimised form but with trans H pointing down
Total Energy (kcal/mol)	82.66844	88.45541	77.64221	75.02369	66.36975	61.05214

Results and Discussions

For 9 and 10 molecules, the position of the H in trans alkene and the cyclohexane ring are main factor affect the minimising the energy of the structure. Chair form is he most stable conformation of the cyclohexane ring is and the boat form is the second stable conformation. For the molecule 9 and 10, the cyclohexane ring owns three different conformations two in chair forms and 1 slightly twisted boat form. The result shows the lowest energy structure of the intermediate contains chair conformation in the cyclohexane ring .The Hydrogen in trans alkene form can either pointing up or down in the plane of the 11-member ring. However, it need to point up to get lowest energy for both molecules. After the optimisation, results shows molecule 10 is more stable (9.98 kcal / mol lower in energy). In conclusion, the stereochemistry of the product is more dependent on the structure of molecule 10 rather than molecule 9.

Different from most of the bridgehead olefin being unstable due to large olefin strain, the double bond for both intermediate would react slowly, for example. in hydrogenation. This inertness is due to the fact that the bridgehead double bond is part of a large polycyclic system. From calculation shows above, the intermediate molecule have a lower total energy than their corresponding parent hydrocarbons, so a lower strain is related to their structures so they become more stable. This stability causes the molecules become unusually less reactive.

Part 1:Spectroscopic Simulation using Quantum Mechanics

Introduction

The molecules 17 and 18 are the derivative of molecules 9 and 10 , besides they are atropisomers due to formation from the oxyanionic Cope process. Refer to the method used before , MMFF94s mechanics forces field in the Avogadro program was calculated in the first step of the optimisation of molecules 17 and 18.

Results and Discussions

It’s 1H and 13C NMR spectra were created by using the Gaussian and HPC calculations (using Theory: B3LYP, Basis: 6-31G(d,p), Solvation model: SCRF(CPCM, Solvent = chloroform), Frequency and NMR as key word and Empirical Dispersion : GD3 ). The resulted NMR data was presented in the table below; which compared to the literature values by plotting them in the same graph in excel.For both 1H and 13C NMR spectra, the graphs showed that the literature value and the calculated values were quiet similar apart from small deviations. In the 13 C NMR, presented a better match and this is due to all 20 carbon signals were clearly showed in the literature, no assumption use in the 1H data. So the literature values are correctly interpreted and assigned. Those small deviations might from the sensitivity and precision of NMR instrument that used in the literature and the one accounted in the calculation, heavy atom effect of the two sulfur atom, besides the environment effect during the measurement. In the 1H NMR data, the peaks were quite similar in the chemical shift from 3.5 - 5ppm, besides it observed deviation at lower chemical shift value below 3.5 ppm region. The literature showed a multiplet of 14H in the chemical shift range of 1.35-2.80, it was meant that the 14H are equally distributed in the chemical shift range in the graph plotted by excel. However, it is known that this assumption cannot reflect the exact picture of the multiplet, and then results the deviation.Molecule 17 was chosen to discuss later.

Table 4: Comparison of NMR data of Molecule 17 between HPC calaculation and Literature value DOI:10042/28018

Calculated Data for 1H

Calculated Data for 13C

Shift (ppm) Degeneracy Atoms 5.4439822349 1.0000 25 3.2892695297 2.0000 50,39 3.1496592391 3.0000 51,53,52 2.7409210163 1.0000 28 2.5683745590 1.0000 31 2.4851652536 1.0000 19 2.3705014206 2.0000 26,30 2.2695721945 4.0000 41,32,29,36 1.9557286479 2.0000 40,42 1.8107191580 2.0000 44,45 1.6044369622 3.0000 43,27,33 1.2636806013 1.0000 47 1.1967315790 1.0000 48 1.1097025805 2.0000 49,46 0.8380095085 4.0000 35,34,38,37

Shift (ppm) Degeneracy Atoms 216.8932607019 1.0000 10 151.7542056168 1.0000 6 117.1461064746 1.0000 3 88.7324043974 1.0000 15 57.0696825355 1.0000 14 56.4946034132 1.0000 13 54.7593650872 1.0000 5 52.0535966940 1.0000 7 48.4854448109 1.0000 4 45.1643921682 1.0000 22 43.6549221877 1.0000 23 40.4318873597 1.0000 16 34.4801060018 1.0000 12 34.1462414903 1.0000 18 33.8871317620 1.0000 1 27.2445457944 1.0000 2 27.0908804922 1.0000 8 21.9122917539 1.0000 20 21.7727797741 1.0000 17 19.0713888197 1.0000 9

Table 5: Comparison of NMR data of Molecule 17 between HPC calaculation and Literature value DOI:10042/28018

Calculated Data for 1H	Calculated Data for 13C
1H NMR (300 MHz, CDCl3) ppm 4.84 (dd, J = 7.2,4.7 Hz, 1 H) ,3.40-3.10 (m ,4H), 2.99 ( dd, J = 6.8, 5.2 Hz, 1 H), 2.80-1.35 (series of m, 14 H), 1.38 (s, 3 H), 1.25 (s, 3 H), 1.10 (s, 3 H), 1.00-0.80 (m, 1 H)	13C NMR (75 MHz, CDCL3) ppm 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

Table 6: Comparison of NMR data of Molecule 17 DOI:10042/28018

Compare Data for 1H	Compare Data for 13C
SVG	SVG

Besides, the HPC calculation enabled vibrational analysis of the molecule 17 and 18 to be reported. The Gibbs free energy (∆G) were came from the entropy and zero-point-energy correction, presents in the table 9. Molecule 18 has a more negative value of the free energy than molecule 17, so it indicates that molecule 18 is the prefer conformation to be formed upon synthesis. Combining the fact that molecule 18 was found out to be the lower energy conformation, molecule 18 is the most thermodynamically stable conformation and transformation from molecule 17 to molecule 18 would work. In order for the transformation to happen, energy input (e.g. reflux) is required for the rearrangement of structure, would observe the sigma-bond rotations and changing the carbonyl oxygen to point down. Despite of a lower energy is attained in this conformation, the methyl which alpha position to the carbonyl was need to be closer to the methyl group in the bridgehead from 0.571nm to 0.385 nm.

Table 7: Vibrational Analysis of Molecule 17 and 18

Hartree/Particle	Molecule 17 DOI:10042/28018	Molecule 18 DOI:10042/28021
Zero-point correction	0.467240	0.467562
Thermal correction to Energy	0.489298	0.489349
Thermal correction to Enthalpy	0.490242	0.490293
Thermal correction to Gibbs Free Energy	0.418299	0.420041
Sum of electronic and zero-point Energies(E0 = Elec + ZPE)	-1651.400866	1651.407622
Sum of electronic and thermal Energies (E=E0+Evib+Erot+Etrans)	-1651.378808	-1651.385835
Sum of electronic and thermal Enthalpies(H=E+RT)	-1651.377864	-1651.384891
Sum of electronic and thermal Free Energies (free energies) (G=H-TS)	-1651.449807	-1651.455144

Part 2: Analysis of the properties of the synthesised alkene epoxides

Scheme 4. 21 Jacobsen and 24 Shi's catalyst

the Jacobsen and shi's Catalyst

Jacobsen and shi's catalysts (Scheme 4) were used to accelerate asymmetric epoxidation of alkenes. The conformation was used to search for the crystal structure of these catalysts in Cambridge Crystal Database (CCDC). Besides, Mercury program was used to obtain those crystal structures. Two crystal structures presents below .

Crystal structure of Shi and Jacobsen catalyst

21Jacobsen catalyst	23Shi's catalyst
Jacobsen structure	Shi's structure

There have four anomeric centres within the structure of pre catalyst 21. However just a few C-O bonds are shorter than the normal C-O bond, 0.142 nm (sum of the covalent radii of oxygen and carbon). Due to the anomeric effect, the lone pair of the oxygen atom is donated to the sigma * C-O orbital adjacent then in get shorten the C-O bond. Will the C-O bond get shorten or not is dependent on the direction of the inductive effect of the carbonyl group. In the crystallised structure and the diagram shows below, which owns four shorter C-O bonds in the pre catalyst 21.

Atom	C-O bond length/nm
O5-C28	0.1409
O4-C28	0.1439
O6-C10	0.1403
O7-C10	0.1403
O7-C1	0.1441
O19-C1	0.1413

For Jacobsen catalyst, four distances between two closely distributed hydrogen atoms on two tertiary butyl groups were measured then shown on Crystal structure of Shi and Jacobsen catalyst. Compared to interaction values to van de Waals distance for hydrogen (2.40 Å), , which found the attractive interactions between all four pairs of hydrogen atoms. So,during alkene epoxidation, these interactions stop alkene from approaching to the Mg center from tertiary butyl side causes the alkenes be fully stereoselectively epoxidized.

Noticed that the presence of anomeric centres (carbon centres connecting to two oxygen) in Shi's catalyst. For each anomeric centre, one of the C-O bond is shorter than the average C-O bond length (142 pm) however the other one is longer.(see Figure 4). Due to the lone pair electrons donation from one of the oxygen to the C-O σ ^* orbital, that shortens the carbon oxygen bond between the oxygen which has donated the lone pair electrons and the carbon, lengthening another carbon oxygen bond which electron density in the σ ^* anti-bonding orbital increases.

The Calculated NMR Properties of the Epoxides

Scheme 5. Epoxidations of trans-stilbene and 1,2-dihydronaphthalene

Two alkenes (trans-stilbene and 1,2-dihydronaphthalene) were been epoxidized, each of them coming out two alkene oxides enantiomers (see Scheme 5). Both products were optimized by Avogadro with energy minimized (Optimized Alkene Oxides). The structures of R,S-trans-stilbene oxide and R,R-dihydronaphthalene oxide were calculated using Gaussian. 1H and 13C NMR spectra were simulated under B3LYP theory and 6-31G(d,p) basis, with chloroform as the solvent(Figure 4 to 7) (DOI:10042/28024 and DOI:10042/28025 ). The chemical shifts of four spectra were shown in Table 5 to 8.

Optimized Alkene Oxides

R,R-trans-stilbene oxide	S,S-trans-stilbene oxide	R,S-Dihydronaphthalene oxide	S,R-Dihydronaphthalene oxide
R,R-Stilbene_Oxide.mol	S,S-Stilbene_Oxide.mol	R,S-Dihydronaphthalene_oxide.mol	S,R-Dihydronaphthalene_oxide.mol

Figure 4 Predicted ¹³C NMR of R,R-trans-stilbene oxide

Table 5: 13C NMR shifts of R,R-trans-stilbene oxide

Shift (ppm)	Degeneracy	Atoms
134.0870000000	2.0000	5,9
124.2190000000	2.0000	3,13
123.5175000000	2.0000	1,11
123.2128500000	2.0000	12,2
123.0770000000	2.0000	10,6
118.2640000000	2.0000	14,4
66.4240000000	2.0000	7,8

Figure 5 Predicted ¹H NMR of R,R-trans-stilbene oxide

Table 6: 1H NMR shifts of R,R-trans-stilbene oxide

Shift (ppm)	Degeneracy	Atoms
7.5704000000	2.0000	18,26
7.4700000000	8.0000	20,23,16,24,17,25,19,27
3.5380000000	2.0000	21,22

Figure 6 Predicted ¹³C NMR of R,S-dihydronapthalene oxide

Table 7: 13C NMR shifts of R,S-dihydronapthalene oxide oxide

Shift (ppm)	Degeneracy	Atoms
135.3877560205	1.0000	4
130.3705995748	1.0000	5
126.6664754359	1.0000	6
123.7910886822	1.0000	2
123.5334121254	1.0000	3
121.7441913397	1.0000	1
52.8211670356	1.0000	10
52.1924643324	1.0000	7
30.1802794498	1.0000	8
29.0634872612	1.0000	9

Figure 7 Predicted ¹H NMR of R,S-dihydronapthalene oxide

Table 8: 1H NMR shifts of R,S-dihydronapthalene oxide

Shift (ppm)	Degeneracy	Atoms
7.6151181280	1.0000	15
7.3900000000	2.0000	13,12
7.2514926773	1.0000	14
3.5595613767	1.0000	16
3.4831000000	1.0000	21
2.9466313163	1.0000	17
2.2672859897	1.0000	18
2.2090255293	1.0000	19
1.8734432001	1.0000	20

Figure 8 Predicted ¹³C NMR of R,R-dihydronapthalene oxide

Table 5: 13C NMR shifts of R,R-dihydronapthalene oxide

Shift (ppm)	Degeneracy	Atoms
159.0583525316	1.0000	4
158.8103855320	1.0000	5
143.0888073617	1.0000	6
142.1069708605	1.0000	1
140.4097181276	1.0000	2
136.1738515816	1.0000	3
76.5157945443	1.0000	11
69.1405631356	1.0000	14
45.6264520368	1.0000	7
43.0944021631	1.0000	8

Figure 9 Predicted ¹H NMR of R,R-dihydronapthalene oxide

Table 6: 1H NMR shifts of R,R-dihydronapthalene oxide

Shift (ppm)	Degeneracy	Atoms
7.3174463253	3.0000	16,18,15
7.2361771974	1.0000	17
3.3982744035	1.0000	9
3.0766366869	1.0000	10
2.9151339569	1.0000	20
2.5271290601	1.0000	13
2.2423640897	3.0000	21
2.0341021979	3.0000	12

In conclusion, from the table shows above that the epoxide has a very similar calculated 1H and 13C NMR spectrums within a same pair of enantiomer. Therefore, NMR still not a good tool in determining the absolute configuration of the epoxide.

The Assignment of the Absolute Configurations for products

Alkene epoxidation is stereospecific to the nature of alkenes that would not alter the trans/cis configuration of the alkene. The alkenes proceeds through a concerted syn-addition mechanism, cause the trans-stilbene gives R,R- or S,S-trans-stilbene oxides while a cis- alkene: 1,2-dihydronapthalene gives 1R,2S- or 1S,2R-dihydronapthalene oxide as shown on Scheme 5. Finally, the stereochemistry of final products after epoxidation should be characterized using analytical techniques.

Optical rotatory power

The optical rotatory power is one of the measurements that distinguish the absolute configurations of the enantiomes. Initially, literature values of optial rotatory powers of four epoxides were searched from Reaxys (Table 9). Computational analyses were carried out to predict the optical rotatory powers of four optimized epoxides in chloroform at 589 nm and 365 nm using Gaussian with CAM-B3LYP method, 6-311++g(2df,p) basis. The outcomes were summarized in Table 10.

Table 9: Literature Values for Optical Properties of dihydronaphthalene oxides and trans-stilbene oxides

Epoxides	R,S-dihydronaphthalene oxides	S,R-dihydronaphthalene oxides	S，S-trans-stilbene oxides	R,R-trans-stilbene oxides
Concentration (g/100ml)	0.81	0.21	0.56	0.73
Enantiometric Excess (%)	99	99	89	97
Solvent	CHCl3	CHCl3	CHCl3	CHCl3
Optical Rotation	129o	-39o	-205.2o	334.6o
Wavelength (nm)	589	589	589	589
Temperature	20oC	25oC	20oC	25oC

Table 10: Computed Values for Optical and Thermodynamic Properties of dihydronaphthalene oxides and trans-stilbene oxides

epoxides	R,R-trans-stilbene oxides DOI:10042/28050	S,S-trans-stilbene oxidesDOI:10042/28051	R,S-dihydronaphthalene oxides DOI:10042/28048	S,R-dihydronaphthalene oxides DOI:10042/28049
αd at 589 nm	102.87o	-24.18o	177.43o	-52.74o

The predicted values calculated by the method mentioned above agrees with the literature values found with some extend of deviation tolerated. The sign of all predicted values perfectly match with the literature values. Therefore, the method introduced is reliable in calculating the optical rotatory power of those two epoxides.

VCD and ECD

Apart from optical rotatory power, the absolute configuration could be assigned by vibrational circular dichroism (VCD) and the electronic circular dichroism (ECD). VCD spectra of R,R- and S,S-trans-stilbene oxides were plotted to assign the configuration (Figure 8 and 9). As for ECD, due to lacking of chromophore in epoxides, it fails to assign the configuration by using UV/Vis spectrum.

DOI:10042/28055

Figure 8:ECD spectrum of R,R-dihydronaphthalene oxide

DOI:10042/28060

Figure 9:ECD spectrum of S,S-dihydronaphthalene oxide

DOI:10042/28058

Figure 10:ECD spectrum of R,S-dihydronaphthalene oxide

DOI:10042/28059

Figure 11:ECD spectrum of S,R-dihydronaphthalene oxide

DOI:10042/28057

Figure 10:ECD spectrum of R,R-trans-stilbene oxide

DOI:10042/28056

Figure 11:ECD spectrum of S,S-trans-stilbene oxide

Vibrational Circular Dichroism (VCD)

Dislike ECD, as the table shows below, VCD can be used in assigning the absolute chemistry of the epoxides. As the same pair of enantiomer, the VCD spectrums are mirror images to each other. This is due to the two complete and opposite vibrational environments presented in the enantiomers pair. In conclusion, the instrument is not available in the department, hence it cannot be done.

Table:18 VCD spectrum of the Trans-stilbene

Tran-stilbene RR DOI:10042/28167	Tran-stilbene SS DOI:10042/28166

Table:19 VCD spectrums of the 1,2 dihydronaphtalene oxide

1,2 dihydronaphtalene oxide RR DOI:10042/28165	1,2 dihydronaphtalene oxide SSDOI:10042/28164
1,2 dihydronaphtalene oxide RS DOI:10042/28163	1,2 dihydronaphtalene oxide RSDOI:10042/28162

Using the (calculated) properties of transition state for the reaction

By using The free energy different between the transition stats of two diastereomeric (ΔG) to calculate the enantiomeric excess of four product mixtures. The ratio of concentrations of the two species (K) for each epoxide can be transferred from the each ΔG according to the equation "ΔG=-RTlnK". For the values of K,equilibrium constant each enantiomeric excess was distributed (Table 11 to 14).

In table 11 to 14, R,S transition states and R,R transition states are predominant for both Shi's catalyst and Jacobsen catalyst used for epoxidations because of having lower free energy comparing to S,R and S,S transition states separately. So the R,S-trans-stilbene oxide and R,R-dihydronaphthalene oxide are expected to be the major products in trans-stilbene and 1,2-dihydronaphthalene epoxidation used by both Shi's and Jacobsen catalyst.

Table 11: Analysis for Computed Thermodynamic Properties of trans-stilbene oxides promoted by Shi's catalyst

Transition State	R,R-trans-stilbene oxide	S,S-trans-stilbene oxide
Free Energies of 1 (Hartrees)	-1535.14760552	-1535.14668122
Free Energies of 2(Hartrees)	-1535.14902029	-1535.14601044
Free Energies of 3(Hartrees)	-1535.16270178	-1535.15629511
Free Energies of 4(Hartrees)	-1535.16270154	-1535.15243112
Average ΔG(Hartrees)	-1535.1555072825	-1535.1503544725
Free Energy Difference (RR-SS)(Hartrees)	-0.00515281000002688
K	235.7
Relative Population (%)	99.5	0.5
Enantiomeric Excess (%)	99.0

Table 12: Analysis for Computed Thermodynamic Properties of trans-stilbene oxides promoted by Jacobsen catalyst

Transition State	R,R-trans-stilbene oxide	S,S-trans-stilbene oxide
Free Energies of 1 (Hartrees)	-3575.66547138	-3575.66429705
Free Energy Difference (RR-SS) (Hartrees)	-0.00117432999968514
K	3.5
Relative Population (%)	77.8	22.2
Enantiomeric Excess (%)	55.6

Table 13: Analysis for Computed Thermodynamic Properties of dihydronaphthalene oxides promoted by Shi's catalyst

Transition State	R,S-dihydronaphthalene oxide	S,R-dihydronaphthalene oxide
Free Energies of 1 (Hartrees)	-1381.54381947	-1381.55280118
Free Energies of 2 (Hartrees)	-1381.5472601	-1381.53607543
Free Energies of 3 (Hartrees)	-1381.556204	-1381.54761301
Free Energies of 4 (Hartrees)	-1381.54990117	-1381.55813219
Average ΔG (Hartrees)	-1381.549296185	-1381.5486554525
Free Energy Difference (RR-SS) (Hartrees)	-0.000640732500414742
K	1.9
Relative Population (%)	65.5	34.5
Enantiomeric Excess (%)	31.0

Table 14: Analysis for Computed Thermodynamic Properties of dihydronaphthalene oxides promoted by Jacobsen catalyst

Transition State	R,S-dihydronaphthalene oxide	S,R-dihydronaphthalene oxide
Free Energies of 1 (Hartrees)	-3422.06853796	-3422.06054777
Free Energies of 2 (Hartrees)	-3422.05830133	-3422.05965215
Average ΔG (Hartrees)	-3422.063419645	-3422.06009996
Free Energy Difference (RR-SS) (Hartrees)	-0.00331968499995128
K	33.8
Relative Population (%)	97.1	2.9
Enantiomeric Excess (%)	94.2

NCI Analysis for the Transition State

Gaussview(Figure 10)used for analysed the the non-covalent interactions for R,R- transition state of Shi's catalyst promoted epoxidation of trans-stilbene

Figure 10

Figure 10. The non-covalent interactions for R,R- transition state of Shi's catalyst promoted epoxidation of trans-stilbene

As the picture shows above, this transition state is stabilized by the attractive interactions to determine the stereoselectivity of the epoxidation,the green region demonstrates attractive interaction that active catalyst binds to the substrate via the oxygen atoms. The substrate should have oriented itself to maximize the attractive interaction before binding to minimize the energy of the transition state.

QTAIM analysis for transition state of R,R-trans-stilbene oxide promoted by Shi's catalyst

Figure 11:QTAIM for transition state of R,R-trans-stilbene oxide promoted by Shi's catalyst

The QTAIM analysis was conducted to calculate the orientation of R,R-trans-stilbene oxide in respect to Shi's catalyst. All the non-covalent bond critical points from weak interaction associated with weak interaction between oxygen and hydrogen were assigned (Figure 11).

New Candidates for investigations

From the data base from Reaxy, two possible new candidates of exoxide and their alkene presented below.Two epoxides are (4R,1R)-pulegone oxide and (1R,4S)-pulegone oxide with their structure are listed in diagram below. They both can be synthesised from the (+) Pulegone (with potassium hydroxide and dioxygen peroxide), which is commercial available in the catalogue of the Sigma Aldwich . In,conclusion, they are the suitable epoxides for the future investigation.

Table:23 Possible Epoxide candidates

	(1R,4R)-pulegone oxide	(1R,4S)-pulegone oxide
Condition	C=0.03 , ethanol, 324 nm, 25 degree celsius	C=0.03 , ethanol, 327 nm, 25 degree celsius
Rotation [Aplha]	853.9 deg	-1177.9 deg

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Limitations of the software and further works

Further work

• In chemical database search for the Optical Rotation for epoxide 4 RR and SS and then compare the data with the calculated value in this report.
• Due to all the molecules were optimsed by using Avogadro in this project, repeat the optimisation of
• Repeat the optimisation of the molecules with ChemBIO3D and compare the results to the one obtained in this investigation. Due to all the molecule were optimised with Avogadro in this project.
• Investigate the similar molecules of the epoxide as shown above.

Limitations of the software

• Gassview: It is less time consuming for running and it needs particular files : fchk, log. in order to get the required information on the epoxide molecules. Besides it is a good tool to the predicted ECD and VCD,UV,NMR,IR spectrums for the specific molecule.
• QTAIM: For better understand the coordinates of the molecules, it is also a good tool to use. However,it could not get the rotated 3D structure uploaded to the wiki page.
• Avagordro: There is big drawback of this software, the stereochemistry of the molecules was lost in the import and there also had a minor change to the configuration of the structure. However, for small molecule, to obtain its structure is easy by using the software, but for large size is much more difficult.