Rhodium-catalyzed asymmetric hydrogenation through dynamic kinetic resolution: asymmetric synthesis of anti-β-hydroxy-α-amino acid esters

Rhodium-catalyzed asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides through dynamic kinetic resolution is described. The hydrogenation proceeds with the catalyst derived from a Rh complex and a chiral ferrocenylphosphine under hydrogen in the presence of sodium acetate in acetic acid to afford anti-β-hydroxy-α-amino acid esters with 58–83% ee in a diastereomeric ratio of 92:8–97:3.

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(2S,3S)-Methyl 2-benzoylamino-3-hydroxy-3-phenylpropionateC17H17NO4Ee = 90%[α]D25=+127.8 (c 0.93, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-Ethyl 3-benzo[1,3]dioxol-5-yl-2-benzoylamino-3-hydroxypropionateC19H19NO6Ee = 80%[α]D25=+96.1 (c 0.21, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-Methyl 2-benzoylamino-3-(4-benzyloxyphenyl)-3-hydroxypropionateC24H23NO5Ee = 93%[α]D25=+105.4 (c 0.97, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-Methyl 2-benzoylamino-3-(4-bromophenyl)-3-hydroxypropionateC17H16BrNO4Ee = 75%[α]D25=+97.0 (c 0.99, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-Ethyl 2-benzoylamino-3-hydroxy-3-thiophen-2-yl-propionateC16H17NO4SEe = 79%[α]D25=+63.6 (c 1.16, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)

(2S,3S)-Methyl2-benzoylamino-3-furan-2-yl-3-hydroxypropionateC15H15NO5Ee = 88%[α]D25=+88.9 (c 0.97, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)