Enantioselective Ring Opening of Epoxides by Fluoride Anion Promoted by a Cooperative Dual-Catalyst System

Abstract

An enantioselective method for the synthesis of beta-fluoroalcohols by catalytic nucleophilic fluorination of epoxides is described. Mild reaction conditions and high selectivity are made possible by the use of benzoyl fluoride as a soluble, latent source of fluoride anion. A chiral amine and chiral Lewis acid serve as cooperative catalysts for desymmetrizations of five- through eight-membered cyclic epoxides, affording products in up to 95% ee. The cocatalytic protocol is also effective for kinetic resolutions of racemic terminal epoxides, which proceed with k(rel) values as high as 300.