Progress of Difluoromethyl Heteroaryl Sulfones as Difluoroalkylation Reagents

Due to the uniqueness of fluorine atom and C-F bond, difluoromethylene has special properties. As a bioisostere of an oxygen or a carbonyl group, it plays an important role in medicines, pesticides and materials. Difluoromethyl heteroaryl sulfones, represented by 2-PySO2CF2H (Hu reagent), have been developed recently as difluoromethylation reagents, and widely recognized by synthetic chemists for their ease of preparation, good functional group tolerance and universal applicability to a wide range of carbonyl compounds. Through different types of reactions such as nucleophilic substitution, nucleophilic addition, Julia-Kocienski olefination reaction, and radical-mediated difunctionalization, they introduced difluoromethyl, difluoromethvlene, gem-difluoroalkene and other fluorine-containing groups into aldehydes, ketones, and heterocyclic compounds. For the first time, the synthesis of fluorine-containing organic compounds involved in various difluoromethy I heteroaryl sulfones in the past decade is reviewed from the perspective of reaction types and their application studies.