Transition-metal-catalyzed site-selective γ- and δ-C(sp3)–H functionalization reactions

C(sp3)–H bonds are ubiquitously present in natural raw materials. Direct functionalization of these bonds provides a highly valuable approach to increasing molecular complexity. However, the inertness of these bonds and their high bond-dissociation energies, low acidity, and unreactive molecular orbital profiles make them challenging reaction components. To overcome these hurdles, the site-selective C(sp3)–H functionalization approach has been developed via various strategies that provide distinct, straightforward, and atom-efficient access to constructing C–C and C–X bonds. This review discusses transition-metal-catalyzed site-selective γ- and δ-C(sp3)–H functionalization of simple aliphatic substrates. The purpose of this review is to characterize the current state of the art in transition-metal-catalyzed site-selective γ- and δ-C(sp3)–H functionalization reactions, their mechanisms, and their application in the late-stage functionalization of medicinal compounds and the construction of medicinally important complex molecules.