Biomimetic Organocatalytic Approach to 4-Arylquinolizidine Alkaloids and Application in the Synthesis of (−)-Lasubine II and (+)-Subcosine II

An enantioselective, biomimetic organocatalytic synthesis of 4-arylquinolizidin-2-ones, key intermediates in the synthesis of several Lythraceae alkaloids, was developed. The methodology features S -proline-mediated Mannich/aza-Michael reactions of readily available arylideneacetones and Δ 1 -piperideine. The total syntheses of (−)-lasubine II and (+)-subcosine II as well as the formal syntheses of structurally related Lythraceae alkaloids were achieved. The use of Δ 1 -pyrroline in the Mannich/aza-Michael reaction provides enantiomerically enriched 5-arylindolizidin-7-ones, which are precursors to nonopiate antinociceptive agents.