Chen's Reagent: A Versatile Reagent for Trifluoromethylation,Difluoromethylenation, and Difluoroalkylation in Organic Synthesis†

Methyl fluorosulfonyldifluoroacetate (FSO₂CF₂CO₂Me or MFSDA), often called “Chen's reagent”, is commonly used to synthesize trifluoromethylated and difluoroalkylated compounds. This important reagent was initially developed as an efficient trifluoromethylating agent by Professor Qing‐Yun Chen and co‐workers at Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences in 1989. Since then, this reagent has been widely used in academia and industry for the copper‐mediated trifluoromethylation of aryl, alkenyl, and even some alkyl halides, among others. During the last decade, this reagent was further developed as a difluorocarbene precursor as well as a radical difluoroalkylating agent under visible light promoted redox catalysis. This review aims to briefly highlight the initial discovery, historical development, and synthetic applications of Chen's reagent, and provide some guidelines for readers to use Chen's reagent in their own synthesis.