Photoinduced regioselective difluorination of secondary inert C(sp3)–H bonds in sulfonamides via 1,5-hydrogen-atom transfer

Abstract

Difluorinated compounds are important structural motifs in organic synthesis and medicinal chemistry because fluoride can modulate the properties of various molecules. In this paper, we present an efficient and convenient method for achieving difluorination of inert C(sp³)–H bonds based on an N-directed 1,5-hydrogen-atom transfer (1,5-HAT) strategy. This difluorination approach tolerates various functional groups and allows for the late-stage difluorination of complex molecules. The proposed mechanism involves the formation of an amine radical cation and a radical chain propagation process, which also provides a new avenue of nitrogen-centered radical generation for the 1,5-HAT reaction.