Highly Enantioselective 1,4-Michael Additions of Nucleophiles to Unsaturated Aryl Ketones with Organocatalysis by Bifunctional Cinchona Alkaloids

The development of general and efficient asymmetric organocatalytic additions of malononitrile and nitromethane to 1,5-diarylpenta-2,4-dien-1-ones (cinnamylideneacetophenones) catalyzed by cinchona organocatalysts is reported. The reactions afforded excellent enantioselectivities (up to 99%), high yields (up to 97%), and exclusive 1,4-addition regioselectivities. The potential of these new enantioselective additions lies in the demonstration that organocatalysts bearing primary amino groups in combination with TFA provide effective catalytic systems for the activation of a broad range of aryl ketones under mild conditions to give compounds with high levels of enantioselectivity and yields.