Synthesis of 3,4-disubstituted piperidines by carbonyl ene and Prins cyclizations: a switch in diastereoselectivity between Lewis and Brønsted acid catalysts

Jodi T Williams; Perdip Singh Bahia; John S Snaith

doi:10.1021/ol0266929

Synthesis of 3,4-disubstituted piperidines by carbonyl ene and Prins cyclizations: a switch in diastereoselectivity between Lewis and Brønsted acid catalysts

Org Lett. 2002 Oct 17;4(21):3727-30. doi: 10.1021/ol0266929.

Authors

Jodi T Williams¹, Perdip Singh Bahia, John S Snaith

Affiliation

¹ School of Chemical Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

PMID: 12375929
DOI: 10.1021/ol0266929

Abstract

[reaction: see text] 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.