An Efficient Approach to the Family of 4-Substituted Pipecolic Acids. Syntheses of 4-Oxo-, cis-4-Hydroxy-, and trans-4-Hydroxy-L-pipecolic Acids from L-Aspartic Acid

Article abstract of DOI:10.1016/0040-4039(95)00183-D

Syntheses of 4-oxo-, cis-4-hydroxy-, and trans-4-hydroxy-L-pipecolic acids from L-aspartic acid using hexafluoroacetone as protecting reagent are described.Combination of a Stille cross-coupling reaction with subsequent Lewis acid catalyzed intramolecular Michael addition provides 4-oxo-L-pipecolic acid 5 or trans-6-methyl-4-oxo-L-pipecolic acid.Borohydride reduction of the protected 4-oxo-L-pipecolic acid derivative gives the corresponding cis-4-hydroxy-L-pipecolic acid 8.The trans isomer 10 is obtained in good yield via Mitsunobu inversion. - Key words: 4-Oxo-L-pipecolic acid, 4-hydroxy-L-pipecolic acids, L-aspartic acid, hexafluoroacetone, intramolecular Michael addition, Stille reaction