New Synthetic Approaches for the Construction of Difluoromethylated Architectures

Abstract

Fluorinated compounds occupy a crucial position in the field of agrochemicals, pharmaceuticals, and material science because of their irreplaceable 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, which has been used as a lipophilic hydrogen bond donor and a bioisostere of thiol, hydroxy, or amino group. The excellent properties of CF2H group have stimulated the efforts of many chemists to develop effective strategies for the selective incorporation of 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 of different types of difluoromethylation, which could be classified into the following categories: radical difluoromethylation, transition metal-catalyzed difluoromethylation, nucleophilic and electrophilic difluoromethylation.