Chiral ligand derived from (1S,2R)-norephedrine as a catalyst for enantioselective prochiral ketone reduction

Chiral oxazaborolidines derived from (1S,2R)-(+)-norephedrine and substituted salicylaldehydes were employed in the asymmetric reduction of prochiral ketones using borane dimethyl sulfide as a reducing agent. The secondary alcohols were formed in excellent yields (45–99.8%) with enantioselectivities up to 99.8%. The effect of the substitution in the aromatic ring of the ligand was discussed with the enantioselectivity of the product.

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4-Bromo-2-({[(1S,2R)-1-hydroxy-2-phenylpropyl]amino}methyl)phenolC16H18BrNO2[α]D30=+14 (c 0.3, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (1S,2R)

4-Chloro-2-({[(1S,2R)-1-hydroxy-2-phenylpropyl]amino}methyl)phenolC16H18ClNO2[α]D30=+11.1 (c 0.2, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (1S,2R)

2-({[(1S,2R)-2-Hydroxy-1-methyl-2-phenylethyl]amino}methyl)-4-nitrophenolC16H18N2O4[α]D30=+53 (c 0.2, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (1S,2R)

2-({[(1S,2R)-2-Hydroxy-1-methyl-2-phenylethyl]amino}methyl)phenolC16H19NO2[α]D30=+17.6 (c 0.25, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (1S,2R)

2-({[(1S,2R)-1-Hydroxy-2-phenylpropyl]amino}methyl)benzene-1,4-diolC16H19NO3[α]D30=+28 (c 0.2, CHCl3)Source of chirality: (1S,2R)-(+)-norephedrineAbsolute configuration: (1S,2R)