Highly Enantioselective Michael Addition of α-Substituted Cyano Ketones to β,γ-Unsaturated α-Keto Esters using Bifunctional Thiourea-Tertiary Amine Catalysts: An Easy Access to Chiral Dihydropyrans

摘要

An asymmetric Michael addition of α-substituted cyano ketones to β,γ-unsaturated α-keto esters to form chiral dihydropyrans catalyzed by a series of α-amino acid-derived thiourea-tertiary amines is presented. A novel tyrosine-derived thiourea catalyst was identified as the optimal catalyst providing the desired product in 91-95% yields and with 90-96% ee at a low catalyst loading of 2.0 mol%. The utility of the reaction was exemplified by facile conversion of the dihydropyran product into pharmaceutically useful dihydropyridine.