Highly ortho‐Selective Trifluoromethylthiolation Reactions using a Ligand Exchange Strategy

Abstract

AbstractThe trifluoromethylthio group (SCF3) is a highly privileged modifier for drug molecules. Direct CH trifluoromethylthiolation reactions are highly valuable synthetic tools for the late‐stage modification of drug candidates, which have so far been underexplored. We report a palladium‐catalyzed ortho‐selective mono‐trifluoromethylthiolation reaction of arenes. The reaction proceeds through a key ligand exchange pathway using readily available silver trifluoromethylthiolate (AgSCF3). Acetic acid was found to be crucial to minimize oxidative dimerization of the starting materials and to facilitate the “SCF3−” transfer. We expect this strategy to have broad applications in CH functionalization reactions using a stand‐alone oxidant and various anions.magnified image