Copper-Catalyzed Amide Radical-Directed Cyanation of Unactivated Csp3-H Bonds

A method for site-selective intermolecular delta/epsilon-C-sp(3)-H cyanation of aliphatic sulfonamides is developed using TsCN as the cyanating reagent, catalyzed by a Cu(I)/phenanthroline complex. The mild, expeditious, and modular protocol allows efficient remote C-sp(3)-H cyanation with good functional group tolerance and high regioselectivity. Mechanistic studies indicate that the reaction might proceed through a Cu(I)-mediated N-F bond cleavage to generate an amidyl radical, 1,5-HAT, and cyano group transfer of the resulting carbon radical with TsCN.