A series of novel β-hydroxyamide based catalysts for borane-mediated enantioselective reductions of prochiral ketones

The enantioselective reduction of prochiral ketones with borane in the presence of a chiral ligand has received considerable attention. Hydroxylamine-based chiral ligands with amide and hydroxyl functions in the presence of other co-ordinating groups are highly effective in these asymmetric reductions. The current work presents a simple one step synthesis of a series of β-hydroxyamide-based ligands from the reaction between 3-hydroxy-2-naphthoic acid and chiral amino alcohols and their applications as catalysts in asymmetric borane-mediated reductions of aromatic prochiral ketones in THF. The reductions provided the corresponding secondary alcohols with up to 96% ee and in good to excellent yields (89–99%). DFT calculations at B3LYP/6-31+g(d) level offered theoretical models to account for the enantioselectivity imposed by the chiral ligands in the reductions of the ketones.

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3-Hydroxy-N-[(2S)-2-hydroxy-1-phenylethyl]naphthalene-2-carboxamideC19H17NO3[α]D20 = −188.9 (c 1, CHCl3)Source of chirality: (2S)-2-amino-2-phenylethanolAbsolute configuration: (2S)

3-Hydroxy-N-[(2S)-1-hydroxy-3-phenylpropan-2yl]naphthalene-2-carboxamideC20H19NO3[α]D20 = −91.6 (c 1, CHCl3)Source of chirality: (2S)-2-amino-3-phenyl-1-propanolAbsolute configuration: (2S)

3-Hydroxy-N-[(2S)-1-hydroxy-3-methyl-1,1-diphenylbutane-2-yl]naphthalene-2-carboxamideC28H27NO3[α]D20 = −21.8 (c 1, CHCl3)Source of chirality: (2S)-(−)-2-amino-3-methyl-1,1-diphenylbutane-1-olAbsolute configuration: (2S)

3-Hydroxy-N-[(2S)-2-hydroxy-1,2,2-triphenylethyl]naphthalene-2-carboxamideC31H25NO3[α]D20 = −388.2 (c 1, CHCl3)Source of chirality: (S)-(−)-2-amino-1,1,2-triphenylethanolAbsolute configuration: (2S)

3-Hydroxy-N-[(2S)-1-hydroxy-1,1,3-triphenylpropan-2-yl]naphthalene-2-carboxamideC23H27NO3[α]D20 = −97.8 (c 1, CHCl3)Source of chirality: (S)-(−)-2-amino-1,1,3-triphenylpropane-1-olAbsolute configuration: (2S)

3-Hydroxy-N-[(2S)-1-hydroxy-3-methyl-1,1-diphenylbutane-2-yl]naphthalene-2-carboxamideC25H21NO3[α]D20 = +98 (c 1, CH3CN)Source of chirality: (1S,2R)-(+)-2-amino-1,2-diphenylethane-1-olAbsolute configuration: (1S,2R)

3-Hydroxy-N-[(1R,2S)-cis-2-hydroxy-2,3-dihydro-1H-inden-1-yl]naphthalene-2-carboxamideC20H17NO3[α]D20 = +63.0 (c 1, CH3CN)Source of chirality: (1R,2S)-(+)-cis-1-amino-2-indanolAbsolute configuration: (1R,2S)