STEREOCHEMISTRY OF THE EPOXIDATION OF BICYCLO [ 2 . 2 . 1 ] HEPT-2-ENE AND ITS 7-SYN-SUBSTITUTED DERIVATIVES . A DFT STUDY

The stereochemical aspects of epoxidation of norbornene and its 7-syn-substituted derivatives by performic acid were investigated. Geometry and thermodynamic parameters of transition states and prereactive complexes were computed at the UBHandHLYP/6-31G(d) level of theory. It is shown that the transition states have a pronounced biradical character and a nearly coplanar orientation of the C=C bond and the molecule of performic acid. Transition state analysis revealed that, in the case of the syn-7-hydroxy derivative, the preference for the exo-approach of the oxidant can be explained by the stabilization of transition state with hydrogen bonding. In contrast, a chlorine atom or a methyl group at the 7-syn position facilitated the formation of endo-epoxides due to steric repulsion between the substituent

Later, epoxidation of 7-syn-substituted norbornenes with mCPBA was used to quantify the steric bulk of various groups [22; 23], as shown in Table 2.The observed exo/endo ratios are in line with the amount of the «open space» between the double bond and the substituent, as calculated by Davis and co-workers [23] using Wilcox's approach [24].Polarity factors did not influence the reaction, as shown by the comparison between the outcomes for epoxidation and hydroboration.The influence of methyl and nitrile groups on the epoxidation of bicyclo[2.2.1]hept-2-en-anti-7ols was studied by Gassman [25]: For X = CH 3 , the ratio of exo-to endo-isomers was 78:22, while for X = CN this ratio was 55:45.This was interpreted as evidence of the lesser steric bulk from the nitrile group.Epoxidation of syn-7-bromomethyl-anti-7-bromonorbornene gave approximately equal amounts of the two epoxide isomers [26].
Several cases are known when the bridge-substituted norbornenes undergo preferential exo-attack.It is possible when the polar factor outweighs the steric one.A hydroxyl group is one of such substituents [27; 28].
Despite the significant interest to the epoxidation of substituted norbornenes, the stereochemistry of this process has been computationally studied only by closed-shell PES scanning for the reactions of unsubstituted norbornene, using either a PM3 approach [11] or a spin-restricted variant of B3LYP/6-31G(d) [9; 10].No quantum-chemical investigation has been published so far that would deal with the substituent effects, steric and electronic factors.Therefore, we studied PES's for the reactions of norbornene (1), and its syn-7-substituted derivatives (2-4), with performic acid.Importantly, an earlier investigations of PES's for the epoxidation of ethylene and cyclopropene by peroxyformic acid at the CASS-CF(10,10)/6-31G(d) and UQCISD/ 6-31G(d) levels
Formation of endo-epoxides can be preferred when the exo-face of norbornene is shielded by bulky groups.Brown quantified the influence of methyl substituents in various positions on the stereochemistry of epoxidation with meta-chloroperbenzoic acid (mCPBA) [20].Table 1 shows that only 7-syn-substituents inhibited the exo-attack.This data agrees with the earlier results for the epoxidation of bornylene [21].

Results and discussion
First-order saddle points, which represented the transition states (TS's) for the formation of syn-7-substituted epoxynorbornanes (Fig. 1), as well as the corresponding reactive complexes were on the calculated PES's.
According to the calculations, the activation energy for the formation of exo-epoxynorbornane (1 x ) is 13.13 kJ/mol higher than for the corresponding endo-isomer (1 n ).Steric repulsion between the performic acid and the norbornene core in all transition states leads to the essentially coplanar alignment of the oxidant and the C=C bond (H-O 1 -C 2 -C 3 (α) dihedral angle, Fig. 1).The major destabilizing factor in the TS1 n when compared to TS1 x is a higher deformation energy, arising from the deformation of the rigid molecular framework.Among the noteworthy structural alterations in the TS1 n are the change in the H-C 2 -C 3 -C 4 dihedral angle and the more planar arrangement of the six-membered ring, quantified by the β parameter -an angle between the planes C 1 C 2 C 3 and C 2 C 6 C 5 (Fig. 1, Table 3).The β value for norbornene itself is 111.9° and for TS1 n -116.5°.In contrast to TS1 x and norbornene, the double bond fragment in TS1 n is exo-bent, and thus the C 1 -H and C 2 -H bonds are more eclipsed, leading to the significant torsional strain.Attachment of a chlorine atom or a methyl group to the C 7 leads to a significant increase in the energy of activation of exo-epoxidation compared to unsubstituted norbornene.This manifests itself in the reversal of stereochemistry of epoxidation and the predominant formation of syn-7-methyland syn-7-chloro-endo-epoxynorbornanes (2 n , 3 n ).The observed selectivity can be explained by the steric (van der Waals) repulsion between the substituent and the hydrogen atom of the peracid.
Further analysis of the computational data showed that the syn-7-hydroxyl group in TS4 xa and TS4 xb participates in the hydrogen bonding with the attacking peracid during exo-addition.When the peracid is syn-oriented (TS4 xa ), two hydrogen bonds are formed, and the molecule of performic acid becomes non-planar (the H-O 1 -O 2 -C 8 angle is 63.8°).TS4 xb is characterized by a single hydrogen bond and planar oxidant structure (Fig. 1).Due to the significant stabilizing effect of the hydrogen bonding in transition states TS4 xa /TS4 xb , the exo-approach of the peracid is much more favored over the endo-attack.

Table 3 Bond angles and dihedral angles (°) in compounds 1-4 and the corresponding transition states (UBHandH
Wavefunction analysis for the located TS's indicates the biradical nature of all of these species (Table 4).Interestingly, spin densities on the atoms C 2 and C 3 in the exo-transition states are symbatic with the calculated activation energies of the corresponding reactions.

Conclusions
In this work, we have investigated the potential energy surfaces that correspond to the biradical mechanism of the interaction of norbornene, and its 7-syn-substituted derivatives, with performic acid.All of the located transition states are characterized by the nearly coplanar alignment of the oxidant and the C=C bond.Stereochemistry of the epoxidation is determined by the balance of steric and electronic factors.Thus, a chlorine atom or a methyl group at the 7-syn position facilitate formation of endo-epoxides while syn-7-hydroxyl group significantly stabilizes exo-transition state due to formation of hydrogen bonds.

Acknowledgement
This work has been supported by Extreme Science and Engineering Discovery Environment (XSEDE), which is funded by National Science Foundation grant number OCI-1053575.S. O. also acknowledges the Ministry of Education and Science of Ukraine for financing his academic visit to the University of Oxford (United Kingdom).

Table 1 Influence of the position of a methyl group on epoxidation of substituted norbornenes [17; 20
; 21] Thus, spin unrestricted variant of DFT theory at the UBHandHLYP/6-31G(d) level has been applied in the current study.