Facial selectivity in epoxidation of 2-cyclohexen-1-ol with peroxy acids. A computational DFT study

We addressed the mechanism of epoxidation of 2-cyclohexen-1-ol by locating all the transition structures (TSs) for the reaction of peroxyformic acid ( PFA) with both pseudoequatorial and pseudoaxial cyclohexenol conformers (fi ve TSs for each conformer) and, for purpose of comparison, also those for t he PFA epoxidation of cyclohexene. Geometry optimizations were performed at the B3LYP/6-31G* level, energies refined with single point B3LYP/6-311+G** //B3LYP/6-31G* calculations and solvent effects introduced with the CPCM me thod. Our results can be summarized as follows: (i) all TSs exhibit a spiro -like structure, that is, the dihedral angle between the peroxy acid plane and the forming oxirane plane is closer to 90 degrees than to 0 degrees (or 180 degrees); (ii) there is a stabilizing hydrogen bonding interaction in syn TSs that, however, is partly counteracted by unfavorable entropic effec ts; (iii) syn,exo TSs with hydrogen bonding at the PFA peroxy oxygens are d efinitely more stable than syn,endo TSs hydrogen bonded at the PFA carbonyl oxygen; (iv) facial selectivity of epoxidation of both cyclohexenol confor mers is mostly the result of competition between only two TSs, namely, an a nti,exo TS and its syn,exo counterpart. The latter TS is more stable than t he former one, as stabilization by hydrogen bonding overrides the unfavorab le entropic and solvent effects; (v) calculations correctly predict both th e experimental dominance of attack leading to syn epoxide for both cyclohex enol conformers and the higher syn selectivity observed for the pseudoequat orial as compared to the pseudoaxial derivative. Moreover, also the experim ental relative and absolute epoxidation rates for cyclohexene and cyclohexe nol as well as for pseudoaxial and pseudoequatorial cyclohexenol derivative s are fairly well reproduced by computational data.