Aryl radical-mediated hydrogen atom transfer for α-C(sp3)-H functionalization of N-protected amines.

The selective α-C(sp3)-H functionalization of amines has emerged as a valuable strategy for the rapid construction of structurally diverse and synthetically important amine architectures. Among the various approaches developed for α-amino radical generation, intramolecular radical translocation via hydrogen atom transfer (HAT) has gained significant attention owing to its predictable site selectivity, mild reaction conditions, and broad synthetic versatility. In particular, 1,5-hydrogen atom transfer processes enable the selective activation of α-C(sp3)-H bonds of N-protected amines through kinetically favored six-membered transition states, providing efficient access to α-amino carbon radicals even in complex molecular settings. The strategic use of N-protecting groups as radical precursors or relay elements has further enabled controlled radical translocation and subsequent bond-forming transformations with high regioselectivity. Recent advances in photoredox catalysis, transition-metal catalysis, and electron donor-acceptor (EDA) complex activation have considerably expanded the scope and mechanistic diversity of these transformations. Despite substantial progress, challenges associated with substrate generality, protecting-group design, mechanistic understanding, and enantioselective control continue to limit broader applications. This review provides a focused and mechanistically unified overview of α-C(sp3)-H functionalization of N-protected amines enabled by intramolecular radical translocation. The discussion is organized by radical relay design, activation mode, and downstream functionalization patterns. It critically evaluates the advantages, limitations, and future opportunities in this rapidly evolving area of radical-mediated C-H functionalization.