1. Reaction Design for Nucleophilic Fluorination with Chiral Lewis Base Catalysts
Abigail G. Doyle, Department of Chemistry, Princeton University
Molecules that contain C–F bonds serve as important pharmaceutical agents, agrochemicals, radiotracers for imaging technologies, and performance materials. Nonetheless, very few methods exist to efficiently and selectively generate C–F bonds. We have identified an enantioselective method for the synthesis of β-fluoroalcohols by catalytic nucleophilic fluorination of epoxides. 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 krel values as high as 300. Our current efforts are aimed at elucidating the mechanism of the fluorination reaction and applying this insight to the development of an enantioselective synthesis of β-fluoro amines by fluoride ring opening of aziridines.