Synthesis of 3,4-disubstituted piperidines by carbonyl ene and Prins cyclizations: a switch in diastereoselectivity between Lewis and Brønsted acid catalysts.
[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.
Williams
Jodi T
JT
School of Chemical Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Bahia
Perdip Singh
PS
Snaith
John S
JS