ENANTIOSELECTIVE SYNTHESIS OF SUBSTITUTED PIPECOLIC ACID-DERIVATIVES

Enantiomerically pure 4-piperidones, prepared by asymmetric [4 + 2] Di els-Alder cycloadditon of chiral 2-aminodienes with imines, have been used as starting materials for the synthesis of several derivatives of pipecolic acid. The alpha-amino acid moiety is obtained after the oxi dation of a hydroxy group or a furan ring of a conveniently protected 2-aryl-6-(hydroxymethyl)-4-piperidone. Depending on the starting piper idone and the synthetic strategy, it is possible to obtain D- or L-fun ctionalized pipecolic acid derivatives by a short synthetic procedure. Moreover, a stereoselective epimerization of the alpha-carbon atom of a particular pipecolate allows for the preparation of both cis- and t rans-6-(hydroxymethyl)pipecolic acids, structures related with dipepti de isosteres.