Asymmetric hydrogenation of α-keto phosphonates with chiral phosphine–phosphoramidite ligands

Rh-catalyzed asymmetric hydrogenation of challenging α-keto phosphonates has been developed. With a new chiral phosphine–phosphoramidite ligand, a wide range of α-keto phosphonates were hydrogenated to afford the corresponding (R)-α-hydroxy phosphonates with moderate to good enantioselectivities (up to 87% ee).

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(R)-Dimethyl(hydroxy(phenyl)methyl)phosphonateC9H13O4PEe: 87%[α]D25 = +41.1 (c 1.08, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Diethyl(hydroxy(phenyl)methyl)phosphonateC11H17O4PEe: 87%[α]D25 = +29.3 (c 1.33, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Diisopropyl(hydroxy(phenyl)methyl)phosphonateC13H21O4PEe: 80%[α]D25 = +20.4 (c 1.64, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl((4-chlorophenyl)(hydroxy)methyl)phosphonateC9H12ClO4PEe: 80%[α]D25 = +39.7 (c 1.26, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl(hydroxy(4-methoxyphenyl)methyl)phosphonateC10H15O5PEe: 83%[α]D25 = +38.9 (c 1.32, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl(hydroxy(p-tolyl)methyl)phosphonateC10H15O4PEe: 85%[α]D25 = +48.4 (c 1.19, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl(hydroxy(m-tolyl)methyl)phosphonateC10H15O4PEe: 85%[α]D25 = +33.2 (c 1.52, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl((3,4-dimethoxyphenyl)(hydroxy)methyl) phosphonateC11H17O6PEe: 83%[α]D25 = +25.5 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Dimethyl(1-hydroxyethyl)phosphonateC4H11O4PEe: 50%[α]D25 = −4.4 (c 1.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)