Asymmetric Aza-Diels-Alder Reactions of in Situ Generated ß,ß-Disubstituted α,ß-Unsaturated N-H Ketimines Catalyzed by Chiral Phosphoric Acids.

ABSTRACT

A novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters has been realized by asymmetric aza-Diels-Alder reactions of 3-amido allylic alcohols with oxazolones enabled by chiral phosphoric acid catalysis. A series of aryl/alkyl- and alkyl/alkyl-disubstituted 3-amido allylic tertiary alcohols and 4-substituted oxazolones could be well tolerated in these reactions, producing dihydropyridinones with excellent diastereoselectivities and high enantioselectivities. Mechanistic study and control experiments were performed to shed light on the reaction mechanism, in which a configurationally defined ß,ß-disubstituted α,ß-unsaturated N-H ketimine was proposed as the key intermediate.