Photoinduced Copper-Catalyzed α-C(sp3)–H Azidation of Amines via Aryl Radical-Mediated 1,5-Hydrogen Atom Transfer

α-Azido amines represent valuable and privileged functional precursors for the incorporation of diverse nitrogen-based groups and have broad applications in biological research and drug discovery. However, the catalytic and practical preparation of α-azido amines remains a persistent challenge. Herein, by using a 2-iodobenzoyl group as a radical translocating group, we present a general and mild α-azidation of various readily available cyclic, acyclic, and aromatic amines with TMSN3 in high regio- and diastereoselectivity via a photoinduced copper-catalyzed system. This protocol tolerates a broad array of functional groups and allows for the late-stage azidation of bioactive complex molecules. Mechanistic and density functional theory (DFT) studies support the reductive quenching of the excited-state copper(I) photocatalyst with azide anions for generating the azido radical and Cu(0) complex. The outer-sphere electron transfer (OSET) between the Cu(0) complex and 2-iodobenzamide followed by aryl radical-mediated 1,5-hydrogen atom transfer (HAT) generates the α-aminoalkyl radical. These two radical species then participate in the final cross-coupling through a radical-polar crossover (RPC) pathway to yield α-azido amines.