Enantioselective synthesis of cis- and trans-3,5-disubstituted piperidines. Synthesis of 20S- and 20R-dihydrocleavamine.
[reaction: see text] Diastereoselective alkylation at the carbonyl alpha-position of chiral nonracemic lactams 2 and 3, the former prepared by cyclocondensation of (R)-phenylglycinol with a racemic gamma-substituted delta-oxoester in a process that involves a dynamic kinetic resolution and the latter by a subsequent equilibration, provides access to enantiopure cis- and trans-3,5-disubstituted piperidines. The usefulness of the approach is illustrated with the synthesis of the alkaloids 20S- and 20R-15,20-dihydrocleavamine.
Amat
Mercedes
M
Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028-Barcelona, Spain. amat@ub.edu
Escolano
Carmen
C
Lozano
Oscar
O
Llor
Núria
N
Bosch
Joan
J
D000470:Alkaloids / Q000138:chemical synthesis*; D000478:Alkylation; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C478301:20R-15,20-dihydrocleavamine; D000470:Alkaloids; D007769:Lactams; D010880:Piperidines