Direct anti-selective asymmetric hydrogenation of α-amino-β-keto esters through dynamic kinetic resolution using Ru-axially chiral phosphine catalysts—stereoselective synthesis of anti-β-hydroxy-α-amino acids

The asymmetric hydrogenation of α-amino-β-keto esters using ruthenium (Ru) anti-selectively proceeds via a dynamic kinetic resolution to afford anti-β-hydroxy-α-amino acids with high enantiomeric purities, which are important chiral building blocks for the synthesis of medicines and natural products. A mechanistic investigation has revealed that the Ru-catalyzed asymmetric hydrogenation takes place via the hydrogenation of the double bond in the enol tautomer of the substrate.

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Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-4-methyl-pentanoateC20H23NO4Ee = 100%[α]D23=+33.9 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-cyclobutyl-3-hydroxy-propionateC21H23NO4Ee = 100%[α]D23=+22.3 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-cyclopentyl-3-hydroxy-propionateC22H25NO4Ee = 100%[α]D24=+20.5 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-cyclohexyl-3-hydroxy-propionateC23H27NO4Ee = 100%[α]D25=+14.8 (c 1.10, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-cycloheptyl-3-hydroxy-propionateC24H29NO4Ee = 100%[α]D25=+12.9 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-pentanoateC19H21NO4Ee = 100%[α]D22=+36.2 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-hexanoateC20H23NO4Ee = 100%[α]D22=-18.3 (c 0.96, CHCl3)Source of chirality: MeO-BIPHEPAbsolute configuration: (2S,3S)

Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-4,4-dimethyl-pentanoateC21H25NO4Ee = 79%[α]D22=+23.9 (c 1.00, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)

Methyl (2S,3S)-2-benzoylamino-3-cyclohexyl-3-hydroxy-propionateC17H23NO4Ee = 96%[α]D26=+35.5 (c 1.07, CHCl3)Source of chirality: BINAPAbsolute configuration: (2S,3S)