C–H Bond Halogenation: Unlocking Regiodivergence and Enhancing Selectivity through Directing Group Strategies

Abstract

Organohalides represent a crucial class of compounds extensively employed as key precursors for organometallic reagents, bioactive molecules, and nucleophilic substitution reactions. Furthermore, the growing prominence of cross-coupling reactions has significantly enhanced the importance of aryl halides, positioning them as essential building blocks in organic synthesis. Recent advancements in C–H functionalization have highlighted the strategic role of directing groups, where functional groups act as internal ligands to facilitate C–H activation. This approach has emerged as a highly efficient strategy for forming C–C and C–X bonds with exceptional regioselectivity from otherwise inert C–H bonds. This review highlights the recent progress in the application of various functional groups, including carboxylic acids, aldehydes, amides, 8-aminoquinoline, N-oxide, PIP, pyridine, and other heterocyclic systems, as directing groups in C–H halogenation reactions over the past five years.