Site-Selective α-C(sp 3 )-H Bond Functionalization of Amines/Amides via 1,2-Hydrogen Atom Transfer

Abstract

Site-selective functionalization of C(sp 3 )-H bond represents a core challenge in modern organic synthesis. The strategy of nitrogen-centered radical-mediated 1,2-hydrogen atom transfer (1,2-HAT) provides an efficient new pathway for the precise α-C(sp 3 )-H bonds functionalization of amines/amides. This article systematically reviews the latest research advances in this field, with a focus on the design and development of nitrogen radical precursors such as N-aroyloxyamides, N-aryloxyamides, N-alkoxyamides, and hydroxamic esters. It delves into the reaction mechanisms and the principles governing chemoselectivity in 1,2-HAT processes under photoredox catalysis, transition-metal-free conditions, and transition-metal synergistic catalysis. The review summarizes the applications of this strategy in the construction of C-C bonds and carbonheteroatom bonds, highlighting its core advantages, including mild reaction conditions, excellent functional group tolerance, high site selectivity, and applicability in the late-stage functionalization of complex molecules. Finally, the current challenges in this field are analyzed, and future research directions and application prospects are discussed.