Synthesis of 3,4-disubstituted piperidines by carbonyl ene and prins cyclizations: A switch in diastereoselectivity between Lewis and Bronsted acid catalysts

[GRAPHIC] A novel diastereoselective approach to cis and trans 3,4-disubstituted piperidines is described. Carbonyl ene cyclization of aldehydes 6a-e catalyzed by the Lewis acid methyl aluminum dichloride in refluxing chloroform affords trans piperidines 8a-e with diastereomeric ratios of up to 93:7. By contrast, Prins cyclization of 6a-e catalyzed by hydrochloric acid at low temperatures affords cis products 7a-e with diastereomeric ratios of up to 98:2.