Recent advances in remote C(sp3)-H functionalization via chelating group-assisted metal-catalyzed chain-walking reaction

Aliphatic C(sp(3))-H moieties are ubiquitous in numerous organic compounds. Direct functionalization of inert C(sp(3))-H bonds is a powerful and straightforward approach for the efficient construction of diverse carbon-carbon or carbon-heteroatom bonds. Chelating group directed metal-catalyzed remote functionalization of readily available alkenes has emerged as an appealing strategy for rapidly accessing various value-added aliphatic molecules. With the aid of directing groups, various alpha-, beta- and gamma-functionalized alkanes could be synthesized smoothly with excellent regioselectivity. The preferred formation of a stable five- or six-membered metallacycle intermediate terminates the chain-walking at a specific methylene site, which serves as the driving force for excellent site-selective migratory functionalization. This review herein is aimed at summarizing the recent progress on the metal-catalyzed regiodivergent functionalization of unactivated alkenes by merging alkene isomerization and cross-coupling with the assistance of directing auxiliary. Last but not least, the current situations and future directions in this field are highlighted and discussed. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.