Preparation of enantiopure 4-oxygenated pipecolic acid derivatives

Article abstract of DOI:10.1016/S0040-4020(97)10059-X

Two approaches to enantiopure 4-ore- 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-(X)-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 highly stereoselective.