Copper-Catalyzed Carbonylative Hydroamidation of Styrenes to Branched Amides

Amides are one of the most ubiquitous functional groups in synthetic and medicinal chemistry. Novel and rapid synthesis of amides remains in high demand. In this communication, a general and efficient procedure for branch-selective hydroamidation of vinylarenes with hydroxyamine derivatives enabled by copper catalysis has been developed for the first time. The reaction proceeds under mild conditions and tolerates a broad range of functional groups. Applying a chiral phosphine ligand, an enantioselective variant of this transformation was achieved, affording a variety of chiral alpha-amides with excellent enantioselectivities (up to 99 %ee) and high yields.