Stereoselective synthesis of (2S,4R)-4-hydroxypipecolic acid

A new synthetic route to enantiopure (2S,4R)-4-hydroxypipecolic acid from commercial ethyl (3S)-4-chloro-3-hydroxybutanoate is reported. The synthesis is based on the Pd-catalyzed methoxycarbonylation of a 4-alkoxy-substituted delta-valerolactam-derived vinyl triflate followed by the stereocontrolled hydrogenation of the enamine double bond. The final product was obtained after exhaustive hydrolysis in 20% yield over 10 steps. ((C)Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).