Direct Catalytic Deaminative Cyanation of Aliphatic Primary Amines

The cyano group is an important and versatile functional group in medicinal chemistry. It is an important target in its own right while also serving as a precursor to other valuable motifs including aminomethyl and carboxamide groups. However, direct deaminative cyanation of aliphatic amines remains a significant challenge due to the inertness of C–N bonds and the instability of amines under oxidative conditions. Herein, we report the first catalytic, direct deaminative cyanation of aliphatic primary amines without preactivation. This method employs an anomeric amide for radical generation from amines and TMSCN as the cyano source, with a copper catalyst and N-fluorosulfonamide reagent cooperatively facilitating both radical coupling and propagation. This work notably represents the first successful integration of anomeric amide activation with a transition metal-catalyzed bond-forming manifold. The process proceeds via in-situ formation of an isodiazene intermediate, with the N–F derived nitrogen-centered radical serving to scavenge the competing HAT process and enable efficient C–CN bond formation. This strategy enables not only efficient cyanation but also asymmetric deaminative cyanation, stereocenter inversion, and downstream transformations such as homologation and CO insertion, offering new tools for diversification of a privileged and abundant precursor.