Rep:Mod:fs1309

Year 3 Computational lab report by feng shen

Part 1

1) The Hydrogenation of Cyclopentadiene Dimer

The Hydrogenation of Cyclopentadiene According to the optimizations, the endo form is the thermodynamically more stable product compared to the exo form. But during the formation of dimer, kinetics factor (the activation energy) plays a much more important role and contradicts the thermodynamic prediction. In this case, the endo transition state is stabilised by the secondary orbital interactions between ᴨ orbitals, while such stabilisation interaction does not happen in the case of exo transition state. Therefore instead of forming the more thermodynamically stable exo product, the reaction proceeds via the pathway with the lower activation energy and forms the endo product.

Table of results from MM2 minimization
Contribution of total energy kcal/mol	product 3	product 4
Stretch	1.28	1.10
Bend	19.87	14.52
Stretch-bend	-0.83	-0.55
Torsion	10.81	12.5
Non-1,4 VDW	-1.23	-1.07
1,4-VDW	5.63	4.51
Dipole/dipole	0.16	0.14
Total	35.69	31.15

As the table shown above suggest, the bend is the most important factor that affect the stability. The reason for the energy difference arises from the position of double bond present in the molecule. As in such 5 or 6 member ring system, the bond angle of a double can no longer maintain as 120° degree and therefore torsional strain and bend arise. The smaller the deviation between actual bond angle and 120°, the more stable the product. According to the bond angle measurement, product 4 has the bond angle of 112°, which is closer to 120° than product 3 does and therefore it’s lower in energy.


product 3	product 4

Reference: 1. Notes from Professor Henry Rzepa on http://www.ch.ic.ac.uk/local/organic/conf/ 19/10/2011

2) Stereochemistry and Reactivity of an Intermediate in the Synthesis of Taxol.

conmparison of total energy between product 9 and 10
	product 9	product 10
Total energy (Kcal/mol)(MM2)	47.84	53.16
Total energy (Kcal/mol)(MMFF94)	70.55	77.87

Further minimization by manually editing the structure was not successful as the same structure was obtained after MM2 optimization for all manual editions.

From MM2 Minimization,product 9 is more stable compared to product 10. Two different results were obtained from MM2 and MMFF94 because different factors are encounter in these 2 different methods. The reasons why alkenes react so slowly is due to the hyper stable nature of the olefins and the presence of equilibrium process as shown on the right. Also the olefin becomes hyper stable as it has less strain than the parent hydrocarbon and therefore and shows decreased reactivity because of the bridgehead location of the double bonds. Such energy difference is termed as olefin strain energy and can be used to interpret and predict the stability and reactivity of the bridgehead alkene.

S. W. Elmore and L. Paquette, Tetrahedron Letters, 1991, 319
See J. G. Vinter and H. M. R. Hoffman, J. Am. Chem. Soc., 1974, 96, 5466
Another well known example is within Vancomycin: J. Am. Chem. Soc., 1999, 121, 3226
An interesting variation is of "atropenantioselective cycloetherification" (G. ÊIslas-Gonzalez, M. ÊBois-Choussy and J. ÊZhu, Org. Biomol. Chem., 2003, 30-32.
First paper formally recognizing the new class of "hyperstable" olefins (Wilhelm F. Maier, Paul Von Rague Schleyer, J. Am. Chem. Soc., 1981, 103, 1891
David K. Johnson and Bradford P. Mundy Tetrahedron Letters Volume 30, Issue 48 , 1989, Pages 6633-6636
Wilhelm F. Maier, Paul Von Rague Schleyer J. Am. Chem. Soc., 1981, 103 (8), pp 1891–1900

3) Regioselective Addition of Dichlorocarbene

Section 1

Surfaces of molecular orbitals using Gaussian
orbital	3D model from gaussian
HOMO
HOMO-1
LUOMO
LUMO+1
LUMO+2	[[Image:LUMO+2.jpg\|thumb\|widthpx\|]

Surface of HOMO obtained from MOPAC method suggests that the double bond endo to the chloride substituent is the most nucleophilic. This is due to the much more diffuse pi* orbital endo to chloride, which results in a better interactions between eletrophile and the double bond, compared to the other double bond.

Section 2 The influence of C-Cl bond on the vibrational frequencies of the molecule.

IR prediction from Gaussian.

Mono Alkene

Diene

Comparison of IR frequencies (^cm-1 )
Functional group	Diene	alkene
C-Cl	693	672
C=C	1736 and 1757	1757

The IR spectra of diene and alkene are different due to the interaction between Cl substituent and the double bond endo to it. Which results in differences in the C-Cl bond and C=C (endo to Cl) IR frequencies. The difference between two double stretching frequecnies arise from the stabilizing antiperiplanar interactions, which strengthens the exo double bond, between the C-Cl σ* orbital and the occupied anti filled pi orbital. This makes the endo double bond more reactive and therefore matches the analysis in part 1.

Reference: B. Halton, R. Boese and H. S. Rzepa., J. Chem. Soc., Perkin Trans 2, 1992, 447

4)Monosaccharide chemistry: glycosidation

1: A methyl group is chosen here to keep the computational demand minimal. Hydrogen atom can not be used here as it tends to form hydrogen bonds between adjacent hydroxyl group. The MM2 method is used here as it also includes interaction between oxygen lone pairs and a better simulation of molecular modelings are obtained using MM2.

Table showing isomers of A and B and their energy
Isomers of A	Conformation	Energy (Kcal/mol)	Isomers of B	Conformation	Energy (Kcal/mol)
Above the Plane A		32.23	Above the Plane B		40.56
Below the plane A'		54.12	Below the Plane B'		56.77

From the table above, the more stable isomers are A and B, they are both simliar to the intermediate in structure.

2: Comparison between C and D.

Comparison between C and D
Intermediate	Conformations	Energy (Kcal/mol)	Stabilization energy=Energy of A-C / B-D (Kcal/mol)
C		31.07	32.23-31.07=1.16
D		52.17	54.12--52.17=1.95

[[media:|...Measurements of bond angles and bond lengths using MM2 and MOPAC/PM6 method ...]]

As the results suggest, both methods show similar results in measuring C-H and C-C bond and they are very close to the optimal data. The difference arises in the case when oxygen get involved, the PM6 method has a greater deviation than the MM2 method does.

Due to the existence of the new 5 member ring, the only possible isomers for C and D may arise from the rotation of C-C bond between C6 and C13.

Possible isomers of C and D.
Isomers	Conformations
C'
D'

Part 2 MIni project

Regio- and stereoselective conversion of alkenes to epoxides

Both 1H NMR and IR spectroscopy techniques can be used here to identify which double bond has been epoxidised.

1) For 1H NMR, only 1 H peak will appear in the alkene hydrogen region if double bond 1 has been epoxidised, while 2 H peaks will appear within the same region if the epoxidation takes place at double bond 2.

2) For the IR spectrum. two different C=C double bond stretches can be observed for the 2 diastereoisomers. This is because the electronegative bromine on double bond 2 can withdraw the electron density from the double bond and results in a weaker bond and therefore lower frequency compared to the other double bond does.

¹³C NMR prediction using Gaussian:

Predication of ¹³C NMR spectrum of compound 14 and 15
Number of carbon atoms in 14	Chemical shift / ppm	Number of carbon atoms in 15	Chemical shift / ppm	comparison to the literature /ppm
6	130.00	6	130.00	129.9
1	131.97	1	131.97	126.5
11	112.79	11	112.79	111.4
5	78.04	5	78.04	74.2
4	77.40	4	77.40	72.7
3	52.17	3	52.17	49.5
2	51.36	2	51.36	48.3
13	32.25	13	32.25	27.5
12	32.20	12	32.20	26.0

The NMR predictions on 13C NMR using Gaussian match the literature very well.

The two diastereoisomers obtained can be explained by analyzing the intermediates of the reaction. The mCPBA or NBS will first attack on one side of the alkene system. If the electrophile attacks from the same side of the acetal group, there will be steric hindrance and electrostatic repulsion between oxygen (mCPBA) or Br (NBS) lone pairs and acetal oxygen lone pairs as shown in the table below. This will result in high kinetic barriers for the reaction to proceed via this pathway. While such interactions in the case of electrophilic attack from the other side of alkene do not exist, the reaction prefers to proceed via a pathway with lower activation energy. The reaction using mCPBA stops at this point by forming epoxide, the other reaction with NBS form a bromonium, which follows by rear site nucleophilic attack by hydroxide ion, after which the oxygen can use its lone pair to replace the adjacent bromine and ends up with epoxide. (see mechanism shown on the right)

Models showing steric and electrostatic interactions
Reagents	Model
mCPBA
NBS

Reference

Germán Fonseca, Gustavo A. Seoane Tetrahedron: Asymmetry Volume 16, Issue 7, 4 April 2005, Pages 1393-1402
T. HUDLICKY,F. RULIN,T. TSUNODA,H. LUNA,C. ANDERSEN,J. D. PRICE, Israel journal of chemistry,Volume 23, Issue 29, page no, July 21, 1992