Selective difluoromethylation and monofluoromethylation reactions

The selective introduction of fluorine atom(s) and fluorinated moieties into organic molecules has become an important and fast-growing research field, since fluorine atoms play crucial roles in life science and materials science-related applications. Similar to the trifluoromethyl group, both difluoromethyl and monofluoromethyl groups can often bring about many beneficial effects to the target molecules, and a variety of CF2H- and CH2F-containing pharmaceuticals and agrochemicals have been developed. Among the synthetic methods for CF2H- and CH2F-containing compounds, selective di- and monofluoromethylation (i.e., introduction of CF2H and CH2F groups into organic molecules) represent one of the most straightforward synthetic methods and thus can be conveniently used in the synthetic design. This feature article summarizes the presently known selective difluoromethylation and monofluoromethylation methods, including nucleophilic, electrophilic, and free radical di- and monofluoromethylation reagents and reactions.