Preparation of enantiopure substituted piperidines containing 2-alkene or 2-alkyne chains: application to total syntheses of natural quinolizidine-alkaloids.

Journal of Organic Chemistry 75(6):1911 (2010) PMID 20155953

A general method for the preparation of enantiopure 2-alkene- or 2-alkyne-containing chain substituted piperidines was established by using nonracemic Betti base as a chiral auxiliary. The key step is that the auxiliary residue was removed by a novel base-catalyzed N-debenzylation via a formation of o-quinone methide mechanism in stead of the traditional hydrogenolysis, by which the alkene or alkyne groups survived. By this method, ten 2-alkene- or 2-alkyne-containing chain substituted piperidines were prepared on the gram scale within a few hours. To demonstrate the efficiency of the method and the versatility of the product, total syntheses of natural alkaloids (+)-pelletierine, (-)-lasubine II, and (+)-cermizine C were achieved by using (S)-2-allyl-N-Boc-piperidine as a versatile building block.

DOI: 10.1021/jo902615u