Direct copper-catalysed deaminative cyanation of aliphatic primary amines

The cyano group is a versatile motif in medicinal chemistry, serving as both a target and a precursor to other functional groups. However, direct deaminative cyanation of aliphatic amines remains a challenge due to the inertness of C–N bonds and the instability of amines under oxidative conditions. Here we report a 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 integrates anomeric amide activation with transition-metal-catalysed bond formation. The strategy enables not only efficient cyanation but also asymmetric deaminative cyanation, stereocentre inversion and downstream transformations such as homologation and CO insertion, providing versatile tools for amine diversification. Direct deaminative cyanation of aliphatic amines is hampered by inert C–N bonds and oxidative instability. Now a copper-catalysed, preactivation-free approach enabled by anomeric amide activation is reported that also includes an asymmetric variant.