Copper-Catalyzed Asymmetric Hydroamination: A Unified Strategy for the Synthesis of Chiral β-Amino Acid and Its Derivatives

Catalytic asymmetric aza-Michael represents one of the most convenient and atom-economical approaches for the rapid construction of biologically active chiral beta-amino acid frameworks. However, the direct enantioselective addition of nitrogen-based nucleophiles to intrinsically low reactivity of alpha, beta-unsaturated carboxylic acid, ester, and amide, as well as simple alpha,beta-unsaturated nitrile, remains a long-standing challenge. Herein, we report a unified Cu-catalyzed asymmetric reversal hydroamination, capable of direct preparation of a series of beta-amino acid, ester, amide, and nitrile in a highly regio- and enantioselective manner, without the requirement of traditional preinstallation of stoichiometric quantities of auxiliaries.