β-Hydroxyamide derivatives of salicylic acid as organocatalysts for enantioselective reductions of prochiral ketones

In order to find the most effective catalyst for the enantioselective reduction of a prochiral ketone, a series of novel β-hydroxyamide derivatives of salicylic acid and chiral amino alcohols were synthesized. Different substituted prochiral ketones have been reduced in high yield (up to 99%) and the corresponding secondary alcohols are formed with good enantiomeric excess (up to 86%). The mechanism of this type of catalyst can be explained by considering the reaction mechanism for the CBS catalyst.

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2-Hydroxy-N-[(1S)-2-hydroxy-1-phenylethyl]benzamideC15H15NO3[α]D20=+33.0 (c 1.12, CHCl3)Source of chirality: (2S)-2-amino-2-phenylethanolAbsolute configuration: (2S)

2-Hydroxy-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]benzamideC16H17NO3[α]D20=-19.0 (c 1.7, CHCl3)Source of chirality: (2S)-2-amino-3-phenyl-1-propanolAbsolute configuration: (2S)

2-Hydroxy-N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]benzamideC21H19NO3[α]D20=+40.0 (c 1, CH3CN)Source of chirality: (1S,2R)-(+)-2-amino-1,2-diphenylethanolAbsolute configuration: (1S,2R)

2-Hydroxy-N-[(2S)-1-hydroxy-3-methyl-1,1-diphenylbutan-2-yl]benzamideC24H25NO3[α]D20=-107.0 (c 1, CHCl3)Source of chirality: (2S)-(−)-2-amino-3-methyl-1,1-diphenyl-1-butanolAbsolute configuration: (2S)

2-Hydroxy-N-[(1S)-2-hydroxy-1,2,2-triphenylethyl]benzamideC27H23NO3[α]D20=-296.0 (c 1, CHCl3)Source of chirality: (S)-(−)-2-amino-1,1,2-triphenylethanolAbsolute configuration: (2S)

2-Hydroxy-N-[(2S)-1-hydroxy-1,3-diphenylpropan-2-yl]benzamideC28H25NO3[α]D20=-95.0 (c 1, CHCl3)Source of chirality: (S)-(−)-2-amino-1,1,3-triphenyl-1-propanolAbsolute configuration: (2S)

2-Hydroxy-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]benzamideC16H15NO3[α]D20=-5.6 (c 1.08, CHCl3)Source of chirality: (1R,2S)-(+)-cis-1-amino-2-indanolAbsolute configuration: (1R,2S)