New Synthetic Approaches for the Construction of Difluoromethylated Architectures

Fluorinated compounds play a vital role in the fields of agrochemicals, pharmaceuticals, and materials science because of their unique lipophilicity, permeability, and metabolic stability. Among all such appealing fluorine-containing functional groups, the difluoromethyl group has attracted considerable attention owing to its outstanding chemical and physical properties. It has been used as a lipophilic hydrogen bond donor and a bioisostere of thiol, hydroxy, or amino groups. The excellent properties of the CF2H group have motivated many chemists to develop effective strategies for the selective incorporation of the CF2H group into target molecules. Over the past decades, a variety of efficient, atom-economical, and facile methods have been discovered for the difluoromethylation of organic substrates. This review summarizes the developments in different types of difluoromethylations, which could be classified into the following categories: radical difluoromethylation, transition metal-catalyzed difluoromethylation, and nucleophilic and electrophilic difluoromethylation.