Asymmetric Syntheses of Enantiopure 4-Substituted Pipecolic Acid Derivatives

Abstract

(2R,4R)-4-Methylpipecolic acid and (2S,4R)-4-hydroxypipecolic acid, two biologically active amino acids, were synthesized using the same strategy. A third amino acid, obtained in a protected form, was also obtained in the same way. The key step of these syntheses involves an intramolecular ene-iminium cyclization which occurs with complete stereoselectivity. The resulting exocyclic double bond can react in a diastereoselective way to afford pure lactones, which can then be efficiently converted into the amino acids.