Enantioselective Mannich Reactions of γ,δ-Unsaturated β-Keto Esters and Application in the Synthesis of β’-Amino enones, 2,6-Disubstituted Piperidin-4-ones and (+)-241D

Enantioselective, organocatalytic Mannich reactions of γ,δ-unsaturated β-keto esters were developed. The Mannich products are readily decarboxylated to the corresponding amino enones, which can be cyclized to enantiomerically enriched 2,6-disubstituted piperidin-4-ones. The strategy is applied in a synthesis of the dendrobatid alkaloid (+)-241 D. Stereoselective reduction of a Mannich product provides a functionalized allylic alcohol with three contiguous stereocenters.