The synthesis of (2S,4R)- and (2R,4R)-4-hydroxypipecolic acid has been realized from commercial ethyl (R)-4-cyano-3-hydroxybutanoate through palladium-catalyzed methoxycarbonylation of a 4-hydroxy-substituted lactam-derived vinyl phosphate followed by the stereocontrolled reduction of the enamine double bond. The stereoselective hydrogenation of the suitably 4-hydroxy-protected enantiomer afforded the cis-(2S,4R)-4-hydroxypipecolic acid product, obtained in 66% overall yield over seven steps. The trans-product (42% overall yield over 8 steps) was instead obtained by hydride conjugate addition to the same α,β-unsaturated ester.

A Short and Convenient Synthesis of Enantiopure cis- and trans-4-Hydroxypipecolic Acid

TABASSO, Silvia;DEAGOSTINO, Annamaria;PRANDI, Cristina
2009-01-01

Abstract

The synthesis of (2S,4R)- and (2R,4R)-4-hydroxypipecolic acid has been realized from commercial ethyl (R)-4-cyano-3-hydroxybutanoate through palladium-catalyzed methoxycarbonylation of a 4-hydroxy-substituted lactam-derived vinyl phosphate followed by the stereocontrolled reduction of the enamine double bond. The stereoselective hydrogenation of the suitably 4-hydroxy-protected enantiomer afforded the cis-(2S,4R)-4-hydroxypipecolic acid product, obtained in 66% overall yield over seven steps. The trans-product (42% overall yield over 8 steps) was instead obtained by hydride conjugate addition to the same α,β-unsaturated ester.
2009
-
3611
3616
https://www.thieme-connect.de/DOI/DOI?10.1055/s-0029-1216979
Ernesto G. Occhiato; Dina Scarpi; Antonio Guarna; Silvia Tabasso; Annamaria Deagostino; Cristina Prandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/132203
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