Enantiopure 2,6-disubstituted piperidines bearing one alkene- or alkyne-containing substituent: preparation and application to total syntheses of indolizidine-alkaloids?

Organic & Biomolecular Chemistry Pub Date: 2010-02-25 DOI: 10.1039/B927007H

Abstract

A general and efficient procedure for the preparation of 2,6-disubstituted piperidines bearing one alkene- or alkyne-containing substituent was developed by using non-racemic Betti base as a chiral auxiliary. Many chiral benzylamines are excellent auxiliaries, but they were rarely used for this purpose because of the inefficient removal of the N-benzyl auxiliary residue under non-hydrogenative conditions. We found that N,N-disubstituted Betti base derivative has a typical Mannich structure of o-naphthol. When it carried out a base-catalyzed formation of o-quinone methide, an efficient non-hydrogenative N-debenzylation was achieved, and the alkene and alkyne groups survived. To demonstrate the efficiency of the method and the versatility of the products, asymmetric total syntheses of indolizidine-alkaloids (?)-167B, (?)-195H, (?)-209D and (?)-223AB were accomplished.

Graphical abstract: Enantiopure 2,6-disubstituted piperidines bearing one alkene- or alkyne-containing substituent: preparation and application to total syntheses of indolizidine-alkaloids
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