Huang Group
School of Chemical Biology & Biotechnology

Weiyu Yin’s work has been published in Adv.Synth.Catal.


Highly ortho-Selective Trifluoromethylthiolation Reactions using a Ligand Exchange Strategy

Weiyu Yin, ZhaofengWang and Yong Huang*, Adv. Synth. Catal. 2014356, 2998 – 3006

The trifluoromethylthio group ([BOND]SCF3) is a highly privileged modifier for drug molecules. Direct C[BOND]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[BOND]H functionalization reactions using a stand-alone oxidant and various anions.