Enantioselective and diastereoselective conjugate additions to α,β-unsaturated carbonyl compounds with bifunctional organic catalysts based on cinchona alkaloids

ORGN 24

Fanghui Wu, fhwu@brandeis.edu and Li Deng, deng@brandeis.edu. Chemistry Department, Brandeis University, MS 015, 415 South Street, Waltham, MA 02454
The conjugate addition of α-substituted 1, 3-dicarbonyl donors to α,β-unsaturated carbonyl compounds provides a powerful strategy for the creation of all-carbon quaternary stereocenters, due to the accessibility of a wide range of both the Michael donors and acceptors and the proven wide utility of the 1,4-adducts. We will present the development and synthetic applications of broadly effective catalytic asymmetric conjugate additions to carbonyl acceptors such as α,β-unsaturated ketones and aldehydes. These reactions utilize readily available bifunctional organic catalysts derived from cinchona alkaloids. The enantioselectivity achieved under modified conditions is unprecedented, ranging from 80-99%. Excellent enantioselectivity(up to 99%) and diastereoselectivity(up to 25:1) were also obtained for reactions with α-substituted α,β-unsaturated carbonyl compounds as Michael donors. The applications of these reactions in catalytic enantioselective syntheses of the biologically interesting natural product will also be discussed.