Site-selective functionalization of remote aliphatic C-H bondsviaC-H metallation

Abstract

Directing group assistance provided a paradigm for controlling site-selectivity in transition metal-catalyzed C-H functionalization reactions. However, the kinetically and thermodynamically favored formation of 5-membered metallacycles has greatly hampered the selective activation of remote C(sp3)-H bondsvialarger-membered metallacycles. Recent development to achieve remote C(sp3)-H functionalizationviathe C-H metallation process largely relies on employing specific substrates without accessible proximal C-H bonds. Encouragingly, recent advances in this field have enabled the selective functionalization of remote aliphatic C-H bonds in the presence of equally accessible proximal ones by taking advantage of the switch of the regiodetermining step, ring strain of metallacycles, multiple non-covalent interactions, and favourable reductive elimination from larger-membered metallacycles. In this review, we summarize these advancements according to the strategies used, hoping to facilitate further efforts to achieve site- and even enantioselective functionalization of remote C(sp3)-H bonds.