Preparation of enantiopure 4-oxygenated pipecolic acid derivatives

✍ Scribed by Yves Bousquet; Paul C. Anderson; Tibor Bogri; Jean-Simon Duceppe; Louis Grenier; Ingrid Guse

• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 646 KB
• Volume: 53
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(97)10059-x

✦ Synopsis

Two approaches to enantiopure 4-oxo-and 4-(R)-hydroxypipecolic acid derivatives from protected L-aspartic acid were developed. The first route exploits an intramolecular Michael addition on the stable enaminone 8. Hydrogenation and concomitant decarboxylation gave the 4-oxo derivative 11 which was reduced selectively to the 4-(R)-hydroxy derivative 12. The second route starts with a Michael addition followed by an intramolecular Dieckmann condensation to build the piperidine ring. The 4-oxo derivatives 11 and 19 are thus obtained in an expeditious manner on large scale without any chromatographic purification. Both sequences proved to be highiy stereoselective.