Proline catalyzed, one-pot three component Mannich reaction and sequential cyclization toward the synthesis of 2-substituted piperidine and pyrrolidine alkaloids

Abstract

A very effective one-pot three component reaction of 4-bromobutanal or 5-bromopentanal, acetone, and p-anisidine catalyzed by proline is reported. A three component Mannich reaction followed by cyclization leading to the synthesis of 2-substituted pyrrolidine and piperidine derivatives through simultaneous formation of two C–N and one C–C bond is reported. The usefulness of the reaction is demonstrated by the synthesis of (±)coniine, (±)pelletrine, (±)sedridine, and (±)allosedridine.