Recent progress in the direct monofluoromethylation of C-H bonds

Fluorine chemistry is of critical importance in the agricultural, pharmaceutical, and materials industries, as the incorporation of fluorine atoms or fluorine-containing groups into organic compounds can significantly enhance their chemical and physical properties. Among these groups, the monofluoromethyl (CH₂F) group has emerged as a distinctive fluorine motif, serving as a metabolically stable and lipophilic bioisostere for functional groups such as NH₂, OH, and SH, and making it a privileged structural unit in drug discovery. As a result, considerable attention has recently been directed toward developing new and practical methods for introducing this group into organic molecules. In this regard, the direct monofluoromethylation of C-H bonds has recently emerged as an ideal strategy, as it does not require pre-functionalized starting materials and allows for more efficient and streamlined synthetic routes. This review highlights recent advances in this area, with particular emphasis on the mechanistic aspects of the reactions.