Radical Decarboxylation-Initiated SH2' Reaction of β,β-Difluoroenol Sulfonates: Access to α,α-Difluoroketones

Org Lett. 2024 Jun 7;26(22):4797-4802. doi: 10.1021/acs.orglett.4c01555. Epub 2024 May 26.

Abstract

Reported herein is a novel radical decarboxylation-initiated SH2' reaction of β,β-difluoroenol sulfonates. This transformation is characterized by mild reaction conditions, a broad substrate scope, and late-stage modification of drug molecules, providing general and mechanistically distinct access to bioactive and synthetically versatile α,α-difluoroketones. Preliminary mechanistic studies demonstrate that this reaction proceeds through a succession of silver-mediated decarboxylative radical generation and radical-addition-induced β-elimination of the sulfonyl radical.