The Enantioselective, Br?nsted Acid Catalyzed, Vinylogous Mannich Reaction

摘要

Asymmetric Mannich reactions are among the most fundamental carbon-carbon bond forming reactions in organic chemistry, and the reaction products are versatile intermediates in the synthesis of chiral, enantiomerically enriched amines.[1] Vinylogous Mannich reactions of ,-unsaturated carbonyl compounds, furnishing highly functionalized -amino ,-unsaturated carbonyl compounds, have established themselves in natural product synthesis.[2] However, only very few catalytic, enantioselective versions have been devised, and these are limited to very special substrate patterns. Building on the results of Martin,[3] Hoveyda, Snapper, and Carswell developed silver-catalyzed, vinylogous Mannich reactions of 2-silyloxy furans, leading to highly enantiomerically enriched butenolides.[4] Chen and co-workers recently reported the first direct asymmetric vinylogous Mannich reaction of ,-dicyanoalkenes and tert-butyloxycarbonyl (Boc)-protected imines with a bifunctional thiourea catalyst, leading to the corresponding products in high yields, excellent enantioselectivities, and complete -regioselectivity.[5] J?rgensen and Niess catalyzed the same reaction successfully under phase-transfer conditions with a chiral pyrrolidinium salt in up to 95 % ee.