Asymmetric Coupling of Carbon-Centered Radicals Adjacent to Nitrogen: Copper-Catalyzed Cyanation and Etherification of Enamides

The first copper-catalyzed asymmetric cyanation and etherification reactions of enamides have been established, where a carbon-centered radical adjacent to a nitrogen atom (CRAN) is enantioselectively trapped by a chiral copper(II) species. Moreover, the asymmetric cyanation of vinyl esters was disclosed as well. These reactions feature very mild reaction conditions and high functional group tolerance, and give a series of chiral alpha-cyano amides, alpha-cyano esters and alpha-hemiaminals in good yields with excellent enantioselectivity. The chiral alpha-cyano amides can be easily converted into enantioenriched 1,2-diamines and amino acids.