Asymmetric synthesis of the four stereoisomers of 4-hydroxypipecolic acid

The asymmetric synthesis of all four stereoisomers of 4-hydroxypipecolic ac id (1) from the polyfunctionalized chiral building blocks delta -amino beta -keto esters (S-S,R)-(+)-5 or (R-S,S)-(-)-5 is described. Key steps in the synthesis are the stereoselective reductions of b-phenylpiperidine-2,4-dio ne (6) and N-sulfinyl delta -amino beta -keto esters 5 to cis 4-hydroxy 2-p iperidinone 7 and syn-delta -amino beta -hydroxy ester 9, respectively. The only protecting/deprotecting group chemistry required is related to the ox idation step.