Enantioselective synthesis of trans-4-methylpipecolic acid.
An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).
Alegret
Carlos
C
Unitat de Recerca en Síntesi Asimètrica (URSA-PCB), Institute for Biomedical Research and Departament de Química Orgànica, Universitat de Barcelona, Parc Científic de Barcelona c/Josep Samitier, 1-5, 08028 Barcelona, Spain.
Santacana
Ferran
F
Riera
Antoni
A
D000499:Allylamine / Q000031:analogs & derivatives; D003500:Cyclization; D004852:Epoxy Compounds / Q000737:chemistry; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism