Copper-Catalyzed Amide Radical-Directed Cyanation of Unactivated C_sp³–H Bonds

Abstract

A method for site-selective intermolecular δ/ε-Csp3–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 Csp3–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.