C–H bond halogenation: unlocking regiodivergence and enhancing selectivity through directing group strategies

Organohalides represent a crucial class of compounds widely used as key precursors for organometallic reagents, bioactive molecules, and nucleophilic substitution reactions. The increasing prominence of cross-coupling reactions has further elevated the importance of aryl halides, establishing them as key building blocks in organic synthesis. Recent advances in C–H functionalization have underscored the strategic role played by directing groups, in which functional groups act as internal ligands to facilitate C–H activation. This method has emerged as a highly efficient approach for forming C–C and C–X bonds with exceptional regioselectivity directly from otherwise inert C–H bonds. This review highlights recent progress in applying various functional groups, including carboxylic acids, aldehydes, amides, 8-aminoquinoline, N-oxides, PIP, pyridine, and other heterocyclic systems, as directing groups in C–H halogenation reactions over the past five years.