C-H Fluoroalkylsulfinylation/Intramolecular Rearrangement for Precise Synthesis of Fluoroalkyl Sulfoxides

Org Lett. 2022 May 13;24(18):3378-3383. doi: 10.1021/acs.orglett.2c01151. Epub 2022 May 2.

Abstract

An efficient methodology to access various fluoroalkyl sulfoxides bearing ortho/para-functionalized amine scaffolds from arylhydroxylamines is described. The transformation was featured with new electrophilic trifluoromethylthiolated reagents, good functional group tolerance, and late-stage modification of complex bioactive scaffolds, providing a rapid access to prepare numerous trifluoromethyl- and difluoromethyl-substituted sulfoxides. Mechanism studies and density functional theory calculations suggest this reaction goes through a nucleophilic trifluoromethylthiolation of arylhydroxylamine and subsequent internal 2,3-sigmatropic rearrangement involving a sulfur and oxygen transfer process.