Asymmetric synthesis of 2,4,5-trisubstituted piperidines from sulfinimine-derived delta-amino beta-ketoesters. Formal synthesis of pseudodistomin B triacetate.
[reaction: see text] N-Sulfinyl delta-amino beta-ketoester enaminones, a new sulfinimine-derived chiral building block, undergoes, on hydrolysis in one pot, an intramolecular Michael addition followed by a retro-Michael-type elimination to give enantiopure 2,4,5-trisubstituted piperidines, a structural motif found in numerous biologically active alkaloids. This new chiral building block is readily prepared by treating N-sulfinyl delta-amino beta-ketoesters with dimethylformamide dimethyl acetal. This new protocol was illustrated with a concise formal asymmetric synthesis of marine alkaloid pseudodistomin B triacetate.
Davis
Franklin A
FA
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA. fdavis@temple.edu
Zhang
Junyi
J
Li
Yingxin
Y
Xu
He
H
DeBrosse
Charles
C
D000080:Acetals / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D003500:Cyclization; D004126:Dimethylformamide / Q000737:chemistry; D004952:Esters / Q000737:chemistry*; D007097:Imines / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013441:Sulfinic Acids / Q000737:chemistry
D000080:Acetals; D000470:Alkaloids; D000588:Amines; D004952:Esters; D007097:Imines; D007659:Ketones; D010880:Piperidines; D013441:Sulfinic Acids; C415192:pseudodistomin B triacetate; D004126:Dimethylformamide