Recent advance in synthetic applications of difluoromethyl phenyl sulfone and its derivatives

Abstract

Organofluorine compounds often possess unique chemical, physical and biological properties and therefore, they play important roles in pharmaceuticals, agrochemicals, and advanced materials. Notably, the introduction of CF2 motif as an oxygen surrogate could significantly improve the metabolic stability and bioavailability of the target molecules. Therefore, selective introduction of the CF2 group into organic molecules is an appealing task. It has been realized that the (phenylsulfonyl)difluoromethyl group is a versatile CF2 building block, which can be readily transformed into other useful fluorinated functionalities such as difluoromethyl (CF2H), difluoromethylene (–CF2–), and difluoromethylidene (=CF2) groups. This article overviews the recent advance of (phenylsulfonyl)difluoromethylation reactions as well as their synthetic applications in organic synthesis within the past decade. Five modes of difluoroalkylation reactions have been developed, including nucleophilic (phenylsulfonyl)difluoromethylations, electrophilic (phenylsulfonyl)difluoromethylations, radical (phenylsulfonyl)difluoromethylations, difluorocarbene reactions, and transition-metal mediated (phenylsulfonyl)difluoromethylations.