Copper-Catalyzed General and Selective α-C(sp3)–H Silylation of Amides via 1,5-Hydrogen Atom Transfer

The development of a general and selective method for α-C(sp3)–H silylation of feedstock amines has been a long-standing challenge. In this paper, we disclose a mild, general, practical, and highly regio- and diastereoselective α-C(sp3)–H silylation of various readily available acyclic, cyclic, and aromatic amines with silylboranes through a copper-catalyzed intramolecular 1,5-hydrogen atom transfer (HAT) strategy. The mild activation of 2-iodobenzamide to generate an aryl radical enabled by a ligand-coordinated silyl copper complex without additional heating or photoinduced conditions, as well as the intramolecular selective 1,5-HAT process to produce the crucial α-aminoalkyl radical species, is the key to the success of this chemistry. This silylation protocol has demonstrated its potential utility in the late-stage modification of structurally complex drugs and bioactive molecules. Therefore, it is expected that this method will find applications in synthetic chemistry and drug discovery.