Asymmetric Tandem Mannich-Michael Reactions of Amino Acid Ester Imines with Danishefsky's Diene

Article abstract of DOI:10.1021/jo00042a027

Imines 1 derived from aromatic, aliphatic, and functionalized aldehydes and various amino acid esters react with Danishefsky's diene under Lewis acid catalysis via a tandem Mannich-Michael mechanism to give cyclic 6-substituted 2,3-didehydro-4-piperidinones in good to high yields and with diastereomeric ratios reaching from 92:8 up to 97:3.The chiral auxiliary is removed by conversion of the α C atom of the amino acid into an acetalic center, employing a Curtius reaction as the key step.For the elucidation of the absolute configuration, the alkaloids (S)-coniine and (R)-δ-coniceine are synthesized from the enaminones 5i and 5r.