Rep:Mod:CHEM126825124225121800

Part 1A - Confirmational Analysis using Molecular Mechanics

The Hydrogenation of Cyclopentadiene Dimer

Compounds 1 and 2

Cyclopentadiene readily undergoes a Diels Alder cycloaddition to form a dimeric product. Dimerisation is stereospecific, and results in the endo product (1) over the exo product (2). A series of optimisations were conducted in Avogadro using the parameters below to obtain the most stable conformations and energies for comparison.

Force Field: MMFF94s
Algorithm: Conjugate Gradients

Compound	TOTAL ENERGY (kcal/mol)	CML
1	55.37610	link
2	58.20369	link

Calculations showed the exo isomer (1) to be more stable by 2.82759 kcal/mol than the endo isomer (2). The experimental observations however show 2 to be formed preferentially over 1 despite 2 being higher in energy.

Chemical reactions are driven by having negative free energy changes, and the larger that change the more thermodynamically stable the product is. However, the activation energy (or barrier) over which the reactants must overcome in order to be converted into products is also important. It can therefore be seen that the dimerisation of cyclopentadiene is controlled by kinetic factors relating to the transition state (i.e. the transition state energy for the formation of 2 is lower than 1 and thus it is formed faster).

Compounds 3 and 4

Compounds 3 and 4 were analysed in a similar fashion to above.

Force Field: MMFF94s
Algorithm: Conjugate Gradients

Compound	Bond Stretching Energy (kcal/mol)	Angle Bending Energy (kcal/mol)	Tortional Stretch Bending Energy (kcal/mol)	Tortional Energy (kcal/mol)	Out-of-plane Bending Energy (kcal/mol)	Van der Walls Energy (kcal/mol)	Electrostatic Energy (kcal/mol)	TOTAL ENERGY (kcal/mol)	CML
3	3.31272	31.98784	-2.10535	-1.51908	0.01282	13.63753	5.11947	50.44595	link
4	2.82708	24.68137	-1.65942	-0.39444	0.00026	10.65877	5.14692	41.26055	link
Difference	0.48564	7.30647	-0.44593	-1.12464	0.01256	-2.97876	-0.02745	9.1854

The biggest difference to the stability of 3 and 4 can be seen in the angle bending energy (4 shows an angle bending energy value 7.30647 kcal/mol less than that of 3). Despite this, many of the values reported in the differences row are actually negative indicating that the value for 4 is greater than 3. Overall however, 4 is lowest in energy.

Atropisomerism in an Intermediate related to the Synthesis of Taxol

[[

Image:Taxol molecules.gif‎|center|400px]]

A variety of conformations of the 6 member ring in Taxol were observed. ChemBio 3D was used to optimise the geometry by a series of energy optimisations and manual manipulation of atoms. Both chair and twist boat conformations were found, with the chairs usually being lower in energy. Interestingly, for Compound 10, one of the chairs found is actually higher in energy than both of the twist boats.

Force Field: MM2

Compound 9

Compound 10

Ring Conformation	Energy (kcal/mol)	CML
Chair 1	47.8395	link
Chair 2	58.3856	link
Twist Boat 1	53.0099	link
Twist Boat 2	65.6336	link

Ring Conformation	Energy (kcal/mol)	CML
Chair 1	52.5418	link
Chair 2	42.6828	link
Twist Boat 1	49.5132	link
Twist Boat 2	46.4335	link

The data obtained shows the most stable antropisomer to be isomer 10, with the 6 membered ring in one of the 2 chair conformations. This conformation has an energy of 42.6828 kcal/mol. This atropisomer is thus likely to react in carbonyl addition reactions.

A series of compounds known as hyperstable alkenes are known in literature^[1]. These compounds are less strained than their saturated hydrocarbon derivatives and thus shown unusual stability to reaction. The energy difference between a hydrocarbon and its olefin derivative is known as the olefin strain energy (OS). By definition, hyperstable alkenes have negative OS values. Bridgehead olefins that have twisted geometries often show hyperstable alkene behaviour. Thus the alkene functionality in isomers 8 and 9 is likely to show reduced reactivity as they contain this motif.

Taxol has indeed been proposed in literature^[2] to exibit hyperstable alkene behaviour when annalysed at the MM2 level.

Part 1B: Spectroscopic Simulation using Quantum Mechanics

Spectroscopy of an intermediate related to the synthesis of Taxol

Both Compounds 17 and 18 were modeled with respect to energy, but the NMR data is only reported for Compound 18. The geometry was optimized in ChemBio3D using an MM2 force field.

Geometries were optimised at the density functional level using B3LYP and a 6-31G(d,p) basis set. An EmpiricalDispersion=GD3 factor was also applied.

Compound	17	18
Geometry
jmol
MM2 Optimised Energy	63.9623 kcal/mol	64.3641 kcal/mol
Free Energy (Sum of electronic and thermal free energies)	-1651.393028 Hartrees	-1651.394012 Hartrees
DOI	DOI:10042/27067	DOI:10042/27068

The data computed for the compounds by quantum mechanics shows Compound 18 to be slightly more stable than 17.

¹H NMR

Compound 18

Computed ¹H Spectrum

Computed ¹H Data
(Benzene)

Experimental ¹H Data^[3]
(300 MHz, C₆D₆)

Chemical Shift (ppm)	Integration
5.97	1H
3.12	2H
2.95	2H
2.89	1H
2.80	2H
2.67	1H
2.54	2H
2.43	1H
2.31	2H
1.98	2H
1.83	2H
1.64	1H
1.53	3H
1.34	1H
1.27	1H
1.21	2H
0.96	2H
0.90	1H
0.60	1H

Chemical Shift (ppm)	Multiplicity	Integration
5.21	m	1H
3.00-2.70	m	6H
2.70-2.35	m	4H
2.20-1.70	m	6H
1.58	t (J = 5.4 Hz)	1H
1.50-1.20	m	3H
1.10	s	3H
1.07	s	3H
1.03	s	3H

¹³C NMR

Compound 18

Computed ¹³C

Computed ¹³C Data
(Benzene)

Experimental ¹³C Data^[3]
(76 MHz, C₆D₆)

Difference

Chemical Shift (ppm)
211.92
147.87
120.12
92.84
65.94
54.94
54.76
49.53
48.03
45.65
44.01
41.47
38.51
33.69
32.47
28.36
26.50
24.44
24.01
22.58

Chemical Shift (ppm)
211.49
148.72
120.90
74.61
60.53
51.30
50.94
45.53
43.28
40.82
38.73
36.78
35.47
30.84
30.00
25.56
25.35
22.21
21.39
19.83

0.43
-0.85
-0.78
18.23
5.41
3.64
3.82
4.00
4.75
4.83
5.28
4.69
3.04
2.85
2.47
2.80
1.15
2.23
2.62
2.75

A comparison of the NMR data to literature.

The ¹³C NMR data computed as a whole agrees well to literature. Although the resonance reported in literature at 74.61 ppm differs largely to that computed of 92.84 ppm, the remaining data is in good agreement.

On the otherhand, the ¹H NMR data shows significant differences to that computed. Many of the multiplets reported in literature that integrated to a number of hydrogens are obtained as seperate resonaces in the computed spectrum. Some peaks are in approximate agreement to that found experimentally. For example, the multiplet reported in literature at 5.21 ppm occurs at 5.97 ppm in the calculated spectrum.

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

Crystal structures of The Shi and Jacobsen catalysts

Pentahelicene

Bond lengths for the the anomeric centre contained within the 6 member ring in the Shi catalysts were found. The O-C-O bond lengths were 1.434 Å and 1.423 Å. Further to this, other C-O bond distances were observed and are labelled in the figure above.

The anomeric effect is usually observed in cyclohexane rings that contain a heteroatom. It is defined by the fact that substituents on carbons next to the atom have a preference for an axial orientations rather than the expected equatorial which would minimise 1,3-diaxial repulsions. A lone pair on the heteroatom is able to overlap with an antiperiplanar antibonding C-X orbital from the substituent in a favourable, stabilising interaction. This shortens the C-O bond between the heteroatom in the ring and the subsituent as it now has more double bond character. Conversely, the C-X bond is elongated as electron density is placed into an antibonding orbital.

Pentahelicene

The closest approach between hydrogens atoms on the adjacent t-butyl groups in the Jacobsen catalyst were measured as 2.421 Å. This gives a carbon - carbon closest approach distance between these groups of 3.696 Å. It should be noted that these are obtained from the crystal structure. It can be inferred that when the molecule 'froze' to crystallise, it would do so in its lowest energy orientation with these t-butyl groups as far apart as possible.

The Van der Walls radius of hydrogen has been determined as 1.20 Å.^[4] Therefore, 2x the VdW radius gives a value that is just less (2.40 Å) than the measured closest approach of 2.421 Å. Therefore, in the crystal state (inferred as the lowest energy as above), there is marginal steric interactions between the t-butyl groups.

Calculated NMR properties of epoxides from Styrene and Trans-stilbene

An epoxide from Styrene - (R)-2-phenyloxirane

¹H NMR

¹³C NMR

Chemical Shift (ppm)	Integration
7.489	4H
7.299	1H
3.662	1H
3.117	1H
2.537	1H

Chemical Shift (ppm)	Integration
135.133	1C
124.135	1C
123.415	1C
122.961	2C
118.273	1C
54.056	1C
53.484	1C

DOI:10042/27069

Coupling Constants

Coupling constants were obtained by running a quantum mechanical calculation. DOI:10042/27340

 
Total nuclear spin-spin coupling J (Hz):
                1             2             3             4             5
      1  0.000000D+00
      2  0.574369D+02  0.000000D+00
      3 -0.151392D+01  0.573242D+02  0.000000D+00
      4  0.982212D+01 -0.207013D+01  0.567495D+02  0.000000D+00
      5 -0.121803D+01  0.939092D+01 -0.134967D+01  0.595917D+02  0.000000D+00
      6  0.577241D+02 -0.211450D+01  0.968070D+01 -0.333490D+00  0.618056D+02
      7  0.440000D+01 -0.177196D+01  0.502033D+01  0.368208D+01  0.556341D+02
      8 -0.878747D+00  0.154325D+01 -0.157807D+00  0.659424D+01 -0.492838D+00
      9  0.167609D+03  0.208042D+01  0.806257D+01 -0.138845D+01  0.752792D+01
     10  0.223460D+01  0.166009D+03  0.200431D+01  0.778470D+01 -0.159630D+01
     11  0.799587D+01  0.185755D+01  0.167057D+03  0.240538D+01  0.745455D+01
     12 -0.106381D+01  0.760809D+01  0.116350D+01  0.165818D+03  0.179055D+01
     13  0.552225D+00  0.759010D+01 -0.122778D+01  0.731163D+01  0.149401D+01
     14  0.744998D+00  0.222256D+00 -0.130634D+00  0.547577D+01  0.408296D+01
     15  0.360732D+00 -0.476003D+00  0.751845D+00 -0.303430D+00  0.120264D+02
     16  0.426009D+00 -0.427786D+00  0.353852D+00 -0.731781D+00  0.661508D+01
                6             7             8             9            10
      6  0.000000D+00
      7  0.233682D+01  0.000000D+00
      8  0.520562D+01  0.729416D+02  0.000000D+00
      9  0.265339D+01  0.627324D+00  0.734431D-01  0.000000D+00
     10  0.798593D+01  0.888566D+00 -0.572611D+00  0.852548D+01  0.000000D+00
     11 -0.143813D+01  0.155293D+00  0.342169D+00  0.101402D+01  0.866338D+01
     12  0.655886D+01  0.676474D+01 -0.251467D+00  0.367007D+00  0.783142D+00
     13  0.164157D+03  0.406130D+01 -0.463702D+00  0.892216D+01  0.735697D+00
     14  0.586432D+01  0.162126D+03 -0.416555D+00  0.504130D+00 -0.385559D+00
     15 -0.517922D+00 -0.512997D-01  0.166786D+03 -0.250424D+00  0.314431D+00
     16 -0.530606D+00 -0.216723D+01  0.162867D+03 -0.115438D+00  0.202286D+00
               11            12            13            14            15
     11  0.000000D+00
     12  0.860881D+01  0.000000D+00
     13  0.469567D+00  0.172501D+01  0.000000D+00
     14 -0.157690D-01 -0.152639D+00 -0.838173D+00  0.000000D+00
     15 -0.129756D+00  0.304893D+00 -0.257744D-01  0.126795D+02  0.000000D+00
     16 -0.314741D+00  0.232354D+00  0.439559D+00  0.181908D+02  0.696814D+00
               16
     16  0.000000D+00

An epoxide from Trans-stilbene - trans–1,2–diphenylethylene oxide [S,S]

¹H NMR

¹³C NMR

Chemical Shift (ppm)	Integration
7.571	2H
7.479	8H
3.537	2H

Chemical Shift (ppm)	Integration
134.088	2C
124.221	2C
123.518	2C
123.212	2C
123.076	2C
118.263	2C
66.425	2C

DOI:10042/27070

Coupling Constants

Coupling constants were obtained by running a quantum mechanical calculation. DOI:10042/27339

Total nuclear spin-spin coupling J (Hz):
                1             2             3             4             5
      1  0.000000D+00
      2  0.603403D+02  0.000000D+00
      3 -0.115501D+01  0.611460D+02  0.000000D+00
      4  0.931627D+01 -0.269161D+00  0.613415D+02  0.000000D+00
      5 -0.110762D+01  0.102534D+02  0.100420D+01  0.633677D+02  0.000000D+00
      6  0.606625D+02 -0.124262D+00  0.105389D+02 -0.193319D+00  0.622889D+02
      7 -0.589146D+00  0.548106D+00 -0.667743D+00  0.509412D+01 -0.555655D+00
      8  0.569435D+00 -0.312655D+00  0.600199D+00 -0.667935D+00  0.495269D+00
      9 -0.335600D+00  0.236087D+00 -0.312703D+00  0.548251D+00 -0.343116D+00
     10  0.544321D+00 -0.335683D+00  0.569360D+00 -0.589211D+00  0.551924D+00
     11 -0.318380D+00  0.219877D+00 -0.319221D+00  0.427289D+00 -0.232671D+00
     12  0.551844D+00 -0.343096D+00  0.495230D+00 -0.555803D+00  0.789643D+00
     13 -0.213892D+01  0.561821D+01  0.223063D+01  0.695447D+02  0.121665D+01
     14  0.185169D+01 -0.134769D+00  0.737420D+01  0.455281D+00  0.730224D+01
     15  0.156421D+03  0.274451D+00  0.816330D+01 -0.136208D+01  0.844501D+01
     16 -0.718645D-01  0.156351D+03  0.109598D+01  0.717877D+01 -0.125338D+01
     17  0.831908D+01 -0.129332D+01  0.153624D+03  0.230372D+01  0.721360D+01
     18  0.823540D+01 -0.101648D+01  0.834429D+01  0.216952D+01  0.151134D+03
     19  0.199188D+00  0.874702D+01 -0.123811D+01  0.715544D+01  0.142082D+01
     20 -0.212057D+00  0.133671D+00 -0.225389D+00  0.309365D+00 -0.197067D+00
     21  0.234419D-01 -0.757270D-01  0.464971D-01 -0.822724D-01  0.378130D-01
     22 -0.204864D+00  0.149832D+00 -0.207106D+00  0.347199D+00 -0.203496D+00
     23  0.216012D-01 -0.671917D-01  0.447700D-01 -0.114347D+00  0.303178D-01
     24 -0.217186D+00  0.159494D+00 -0.888279D-01  0.282248D+00 -0.105807D+00
     25  0.342470D+00  0.164536D+00  0.989268D+01  0.103757D+01  0.711774D+01
     26 -0.459746D+00  0.381101D+00 -0.758563D+00  0.598834D+01 -0.538683D+00
                6             7             8             9            10
      6  0.000000D+00
      7  0.427356D+00  0.000000D+00
      8 -0.319286D+00  0.613456D+02  0.000000D+00
      9  0.219865D+00 -0.269613D+00  0.611395D+02  0.000000D+00
     10 -0.318541D+00  0.931577D+01 -0.115521D+01  0.603474D+02  0.000000D+00
     11  0.226513D+00 -0.193500D+00  0.105372D+02 -0.124444D+00  0.606585D+02
     12 -0.232615D+00  0.633494D+02  0.100325D+01  0.102548D+02 -0.110793D+01
     13  0.471414D+01  0.454811D+00  0.737569D+01 -0.135127D+00  0.185182D+01
     14 -0.767476D+00  0.695511D+02  0.223021D+01  0.561866D+01 -0.213883D+01
     15  0.571986D+00  0.347200D+00 -0.207197D+00  0.149869D+00 -0.204807D+00
     16  0.855148D+01 -0.821676D-01  0.463905D-01 -0.756895D-01  0.235469D-01
     17 -0.780448D+00  0.309282D+00 -0.225429D+00  0.133700D+00 -0.212037D+00
     18 -0.236206D+01  0.282101D+00 -0.887614D-01  0.159482D+00 -0.217422D+00
     19  0.156801D+03 -0.114237D+00  0.446540D-01 -0.671630D-01  0.217569D-01
     20  0.155776D+00  0.230579D+01  0.153631D+03 -0.129332D+01  0.831776D+01
     21 -0.691329D-01  0.717778D+01  0.109593D+01  0.156350D+03 -0.724360D-01
     22  0.146631D+00 -0.136214D+01  0.816412D+01  0.276852D+00  0.156418D+03
     23 -0.756374D-01  0.715644D+01 -0.123851D+01  0.874615D+01  0.199532D+00
     24  0.133966D+00  0.216708D+01  0.834233D+01 -0.101621D+01  0.823611D+01
     25  0.651660D+00  0.598861D+01 -0.759011D+00  0.381346D+00 -0.459659D+00
     26  0.449923D+00  0.103837D+01  0.989358D+01  0.164404D+00  0.342615D+00
               11            12            13            14            15
     11  0.000000D+00
     12  0.622973D+02  0.000000D+00
     13 -0.767042D+00  0.730272D+01  0.000000D+00
     14  0.471203D+01  0.121674D+01  0.705725D+02  0.000000D+00
     15  0.146526D+00 -0.203565D+00  0.949545D+00 -0.708766D+00  0.000000D+00
     16 -0.692341D-01  0.377937D-01 -0.104754D+00  0.324524D+00  0.117587D+02
     17  0.155582D+00 -0.197159D+00  0.936101D+01 -0.205850D+00  0.876609D+00
     18  0.134076D+00 -0.105698D+00  0.500211D+01 -0.409109D+00  0.789382D+00
     19 -0.757643D-01  0.302569D-01  0.614638D+00  0.111608D+00  0.115700D+02
     20 -0.780605D+00  0.721394D+01 -0.206283D+00  0.936035D+01  0.615458D-01
     21  0.855310D+01 -0.125333D+01  0.324518D+00 -0.104615D+00 -0.123831D+00
     22  0.569703D+00  0.844474D+01 -0.708867D+00  0.949479D+00  0.115369D+00
     23  0.156796D+03  0.142083D+01  0.111617D+00  0.614547D+00 -0.122036D+00
     24 -0.235732D+01  0.151136D+03 -0.409157D+00  0.499979D+01  0.406319D-01
     25  0.449441D+00 -0.538991D+00  0.144797D+03 -0.316766D+00 -0.498488D+00
     26  0.651764D+00  0.711871D+01 -0.317531D+00  0.144795D+03  0.318097D+00
               16            17            18            19            20
     16  0.000000D+00
     17  0.120152D+02  0.000000D+00
     18  0.221080D+00  0.248858D+01  0.000000D+00
     19  0.122893D+01  0.103421D+00  0.125247D+02  0.000000D+00
     20 -0.137715D+00  0.662458D-01  0.315729D+00 -0.491621D-01  0.000000D+00
     21 -0.495353D-01 -0.137705D+00 -0.729010D-01 -0.256857D-01  0.120133D+02
     22 -0.123828D+00  0.615172D-01  0.406273D-01 -0.122040D+00  0.876366D+00
     23 -0.256932D-01 -0.491399D-01 -0.136702D+00 -0.535066D-01  0.103554D+00
     24 -0.728783D-01  0.315705D+00  0.982935D-01 -0.136697D+00  0.248842D+01
     25  0.129070D+00 -0.405769D+00 -0.119036D+01  0.725008D+00  0.344295D+00
     26 -0.319480D+00  0.344068D+00  0.318672D+00 -0.111296D+00 -0.405924D+00
               21            22            23            24            25
     21  0.000000D+00
     22  0.117591D+02  0.000000D+00
     23  0.122884D+01  0.115700D+02  0.000000D+00
     24  0.221036D+00  0.789263D+00  0.125243D+02  0.000000D+00
     25 -0.319525D+00  0.318122D+00 -0.111334D+00  0.318711D+00  0.000000D+00
     26  0.129124D+00 -0.498484D+00  0.725226D+00 -0.119044D+01  0.182685D+02
               26
     26  0.000000D+00

The reported literature for optical rotations

Reaxys was searched using specific stereoisomers. All values reported in Reaxys at 589 nm in the correct solvent were analysed and then averaged. In the case of (R)-2-phenyloxirane, the sign of the value reported was variable. Details of the calculation are available by following the links in the table below. Only values reported in chloroform were used to determine the literature average as this was the solvent used in the computations.

Epoxide	Stereochemistry	Average Literature Optical Rotation at 589 nm
2-phenyloxirane	[R]	- 22.42 ^o Link to data summary
trans–1,2–diphenylethylene oxide	[S,S]	- 227.10 ^o Link to data summary

The calculated chiroptical properties of the product

Epoxide	Stereochemistry	OR	ECD	VCD
2-phenyloxirane	[R]	-30.37 ^o	Click here for spectra	Click here for spectra
2-phenyloxirane	[R]	DOI:10042/27088	DOI:10042/27091	DOI:10042/27090
trans–1,2–diphenylethylene oxide	[S,S]	-298.12 ^o	Click here for spectra	Click here for spectra
trans–1,2–diphenylethylene oxide	[S,S]	DOI:10042/27096	DOI:10042/27097	DOI:10042/27098

The calculated optical rotation for (R,R)-2-phenyloxirane agrees very well to the average value obtained from a literature search. That of trans–1,2–diphenylethylene oxide however does not agree as favorably.

Using the calculated properties of the transition state for the reaction

Using the following equations, and free energies reported for the transition states by quantum mechanical calculations, the enantiomeric excess for the products of the epoxidation of trans-β-methyl styrene using two different catalysts are shown below.

Δ $G = - R T l n K$

$E n a n t i o m e r i c E x c e s s = | \frac{K - 1}{K + 1} | * 100 %$

Shi Catalyst Epoxidation of trans-β-methyl styrene

The table below reports the energy of the lowest transition state provided in the experimental script, for each of the possible stereoisomeric products with the specific catalyst used.

Transition States	Stereochemistry	Energy TS
Shi Epoxidation of trans-β-methyl styrene	R,R	-1343.032443
Shi Epoxidation of trans-β-methyl styrene	S,S	-1343.024742

ΔE (Hartrees)		-0.007701
ΔE (kJ/mol)		-20.21897704
K		3500.996818
Enantomeric Excess		99.943 %

This calculated enantiomeric excess predicts an excess of the (R,R) diastereoisomer to be formed.

A literature search^[5] yielded results from previous experimental work that supported these conclusions - i.e. that the (R,R) enantiomer was made selectively.

Jacobsen Catalyst Epoxidation of trans-β-methyl styrene

Transition States	Stereochemistry	Energy TS
Jacobsen Epoxidation of trans-β-methyl styrene	R,R	-3383.254344
Jacobsen Epoxidation of trans-β-methyl styrene	S,S	-3383.262481

ΔE (Hartrees)		0.008137
ΔE (kJ/mol)		21.3636951
K		0.000179949
Enantiomeric Excess		99.996 %

The Jacobsen epoxidation^[6] is known to prefer cis alkene subjects to enantiopure epoxidations. Although examples of the epoxidation of cis-β-methyl styrene could be found in literature, the equivalent for trans-β-methyl styrene were not found.

Investigating the non-covalent interactions in the active-site of the reaction transition state

The TS for (R,R)-trans-β-methyl styrene was investigated using the Shi catalyst.

The following parameters were used:
- Type = Total Density
- Grid = Fine

Orbital

In the above images, a number of interactions can be observed. Those in green are weakly attractive, in blue strongly attractive, in yellow are weekly repulsive and in in red are strongly repulsive. A new bond can be seen to be forming in the right hand image between the C-C of the alkene in the starting material and an oxygen atom on the Shi catalyst. Extensive green areas are observed on the NCI analysis which indicate substantial non covalent interactions occuring in the active site of the reaction transition state.

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

The TS for (R,R)-trans-β-methyl styrene was investigated.

QTAIM View 1	QTAIM View 2	QTAIM View 3

Bond critical points can be identified in the above diagram as yellow spheres. Interestingly some BCPs do not lie along bonds. Furthermore some do not lie exactly between nuclei as might be expected. In the right hand image BCPs have been highlighted with green boxes. The NCP located at the top right of the image does not lie in the place of a traditional covalent bond and is involved with the bond forming in the transition state of the reaction.

Two further BCPs (yellow spheres) have been highlighted in the green box towards the bottom left of the image. These do relate to covalent bonds but illustrate the assymetrical orientation of the BCP related to the bond atoms. This is caused by differences in atom electronegativity.

Suggested new candidates for the investigations

The compound (-)-epiepoformin was chosen as a new canditate for investigation. It's optical rotation has only been reported once in literature as -311 deg (Ethanol, 589nm, 0.27 g/100ml).^[7]. A possible synthesis is shown for the compound by epoxidation of the least hindered alkene (i.e. the right hand alkene in the diagram on this page). Furthermore, it is likely the epoxide ring would be placed on the top of the molecule due to steric repulsions from the OH group pointing down in the starting material. This would ensure correct product stereochemistry.

Although the starting material shown is not currently available from Sigma Aldrich, it's synthesis has been achieved by a research group.^[8]. Interestingly the starting material compound shows activity against renal and colon cancers.

References

↑ W. F. Maier, P. Von Rague Schleyer, J. Am. Chem. Soc., 1981, 103, 1891. DOI:10.1021/ja00398a003
↑ C. S. Swindell, T. F. Isaacs, K. J. KanesTetrahedron Letters, 1985, 3, 289-292. DOI:10.1016/S0040-4039(01)80799-1
↑ ^3.0 ^3.1 L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers", J. Am. Chem. Soc., 1990, 112, 227–28.DOI:10.1021/ja00157a043
↑ R. Scott Rowland and Robin Taylor, J. Phys. Chem., 1996, 100 (18), 7384-7391. DOI:10.1021/jp953141+
↑ Z.X Wang, L. Shu, M. Frohn, Y. Tu, Y. Shi, Organic Syntheses, 2003, 80, 9. DOI:10.1002/0471264180.os080.02
↑ E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng J. Am. Chem. Soc., 1991, 113, 7063–7064; DOI:10.1021/ja00018a068
↑ David M. Pinkerton , Martin G. Banwell, Anthony C. Willis Org. Lett., 2009, 11 (19), 4290–4293; DOI:10.1021/ol9016657
↑ Wells G, Berry JM, Bradshaw TD, Burger AM, Seaton A, Wang B, Westwell AD, Stevens MF. J Med Chem., 2003, 13;46(4), 532–541; DOI:10.1021/ol9016657

[ja00398a003-1] W. F. Maier, P. Von Rague Schleyer, J. Am. Chem. Soc., 1981, 103, 1891. DOI:10.1021/ja00398a003

[S0040-4039(01)80799-1-2] C. S. Swindell, T. F. Isaacs, K. J. KanesTetrahedron Letters, 1985, 3, 289-292. DOI:10.1016/S0040-4039(01)80799-1

[ja00157a043-3] 3.0 ^3.1 L. Paquette, N. A. Pegg, D. Toops, G. D. Maynard, R. D. Rogers", J. Am. Chem. Soc., 1990, 112, 227–28.DOI:10.1021/ja00157a043

[href-4] R. Scott Rowland and Robin Taylor, J. Phys. Chem., 1996, 100 (18), 7384-7391. DOI:10.1021/jp953141+

[j0471264180-5] Z.X Wang, L. Shu, M. Frohn, Y. Tu, Y. Shi, Organic Syntheses, 2003, 80, 9. DOI:10.1002/0471264180.os080.02

[10.1021/ja00018a068-6] E. N. Jacobsen , W. Zhang , A. R. Muci ,J. R. Ecker , L. Deng J. Am. Chem. Soc., 1991, 113, 7063–7064; DOI:10.1021/ja00018a068

[epi-7] David M. Pinkerton , Martin G. Banwell, Anthony C. Willis Org. Lett., 2009, 11 (19), 4290–4293; DOI:10.1021/ol9016657

[epi2-8] Wells G, Berry JM, Bradshaw TD, Burger AM, Seaton A, Wang B, Westwell AD, Stevens MF. J Med Chem., 2003, 13;46(4), 532–541; DOI:10.1021/ol9016657

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

Part 1A - Confirmational Analysis using Molecular Mechanics

The Hydrogenation of Cyclopentadiene Dimer

Compounds 1 and 2

Compounds 3 and 4

Atropisomerism in an Intermediate related to the Synthesis of Taxol

Part 1B: Spectroscopic Simulation using Quantum Mechanics

Spectroscopy of an intermediate related to the synthesis of Taxol

1H NMR

13C NMR

A comparison of the NMR data to literature.

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

Crystal structures of The Shi and Jacobsen catalysts

Calculated NMR properties of epoxides from Styrene and Trans-stilbene

An epoxide from Styrene - (R)-2-phenyloxirane

Coupling Constants

An epoxide from Trans-stilbene - trans–1,2–diphenylethylene oxide [S,S]

Coupling Constants

The reported literature for optical rotations

The calculated chiroptical properties of the product

Using the calculated properties of the transition state for the reaction

Shi Catalyst Epoxidation of trans-β-methyl styrene

Jacobsen Catalyst Epoxidation of trans-β-methyl styrene

Investigating the non-covalent interactions in the active-site of the reaction transition state

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

Suggested new candidates for the investigations

References

¹H NMR

¹³C NMR