Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide

Abstract

A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a S_RN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH₂, amide, ester).