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.
Key word
amino acids - carbonylations - coupling - lactams - palladium
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