Chemo- and Regioselective Asymmetric Synthesis of Cyclic Enamides through the Catalytic Umpolung Organocascade Reaction of α-Imino Amides

The efficient chemo- and regioselective catalytic asymmetric syntheses of enamides, which are important core structures of bioactive natural products, have been achieved through the first umpolung organocascade reaction of alpha-imino amides. A variety of enamides have been synthesized enantioselectively in high yields with up to 99% ee. Notably, both enantiomers of the products can be selectively prepared by the simple pretreatment of the substrate. Mechanistic studies reveal that E/Z-geometry information from the substrate is transferred to the product. The present method can be applied to a wide range of alpha-imino amides, irrespective of the electronic nature of the substituents.