Effect of α-fluorination on asymmetric epoxidation of trans-olefins using α-fluorinated cyclohexanone dioxiranes

Abstract

Epoxidations of trans-β-methylstyrene, trans-stilbene and trans-methyl p-methoxycinnamate using chiral dioxiranes derived from both enantiopure diastereomers of α-fluoro cyclohexanones, (2 S, 5 R)- 3a– 6a and (2 R, 5 R)- 3e– 6e are studied and compared. From ab initio calculations at the HF/6–31G ∗ level of conformational inter-conversion for (2 S, 5 R)- D5a and (2 R, 5 R)- D5e dioxiranes it was found that, due to the α-fluorine atom, conformer K1 is more stable in the case of (2 S, 5 R)- D5a while conformer K2 is more stable in the case of (2 R, 5 R)- D5e. However, in both cases, the more stable conformers, K1 and K2, undergo rapid inter-conversion. Therefore, based on slow epoxidation reactions and rapid ring inversion of six-membered ring dioxiranes the Curtin–Hammett principle holds. Conformation K2 with axial fluorine having been found to be more reactive, the inversion of configuration observed for the epoxides obtained with ketones 3e– 6e (compared with ketones 3a– 6a) could be rationalized from competitive reactions of K2 and K1 conformations leading to simultaneous production of both (−) and (+) epoxides in the case of ketones 3e– 6e.