Enantiodivergent Approach to the Synthesis of Cis-2,6-Disubstituted Piperidin-4-ones.

Abstract

Enantiopure β-amino ketone derivatives were synthesized by decarboxylative Mannich reaction of chiral N- tert-butanesulfinyl imines with β-keto acids and were subsequently transformed into cis-2,6-disubstituted piperidin-4-ones through an organocatalyzed condensation with aldehydes. Both enantiomers were accessible from the same precursors by inverting the order in the reaction sequence of the aldehydes involved in the imine formation and the intramolecular Mannich condensation. The synthesis of the piperidine alkaloids (+)-241D, (-)-epimyrtine, and (-)-lasubine II demonstrated the utility of this methodology.