A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane

A novel C3-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity.

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(S)-2-Bromo-1-(4-bromophenyl)-ethanolC8H8Br2O[α]D20=+27.6 (c 0.41, CHCl3), 88% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Bromo-1-(4-methylphenyl)-ethanolC9H11BrO[α]D20=+34.7 (c 0.63, CHCl3), 85% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Bromo-1-(4-nitro-phenyl)-ethanolC8H8BrNO3[α]D20=+34.5 (c 0.27, CHCl3), 50% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-1-Phenyl-propanolC9H12O[α]D20=+37.1 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-Phenyl-butanolC10H14O[α]D20=+30.5 (c 0.2, CHCl3), 70% ee.Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-2-Chloro-1-(4-fluoro-phenyl)-ethanolC8H8FClO[α]D20=+47.0 (c 0.21, CHCl3), 90% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-1,2,3,4-Tetrahydronaphthalen-1-olC12H12O[α]D20=-20.8 (c 0.25, CHCl3), 70% ee.Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-Phenyl-ethanolC8H10O[α]D20=+27.5 (c 0.2, CHCl3), 68% eeSource of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-2-Bromo-1-(4-fluoro-phenyl)-ethanolC8H8BrClO[α]D20=+27.5 (c 0.2, CHCl3), 84% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

2-Bromo-1-(3-bromophenyl)-ethanolC8H8Br2O[α]D20=+22.3 (c 0.95, CHCl3), 90% eeSource of chirality: asymmetric synthesis

2-Bromo-1-(4-fluorophenyl)-ethanolC8H8BrFO[α]D20=+30.6 (c 0.64, CHCl3), 90% ee.Source of chirality: asymmetric synthesis

Tris(3-ethylamino-4-[2(S)-(hydroxyl-diphenyl-methyl)-pyrrolidin-1-yl]-cyclobut-3-ene-1,2-dione)amineC69H69N7O9[α]D23=+33.6 (c 3, DMSO)Source of chirality: l-prolineAbsolute configuration: (S)

(S)-2-Bromo-1-phenyl-ethanolC8H9BrO[α]D23=+48.3 (c 1, CHCl3), 93% eeSource of chirality: asymmetric synthesisAbsolute configuration: (S)

1,3,5-Tris(3-[2-(S)-(hydroxyl-diphenyl-methyl)-pyrrolidin-1-yl]-4-methylamino-cyclobut-3-ene-1,2-dione)benzeneC72H66N6O9[α]D23=+78.6 (c 3, DMSO)Source of chirality: l-prolineAbsolute configuration: (S)

1,3,5-Tris(3-[2-(S)-(hydroxyl-diphenyl-methyl)-pyrrolidin-1-yl]-4-methylamino-cyclobut-3-ene-1,2-dione)-2,4,6-trismethylbenzeneC75H72N6O9[α]D23=+82.7 (c 3, DMSO)Source of chirality: l-prolineAbsolute configuration: (S)

1,3,5-Tris(3-(1R,2S)-(2-hydroxy-indan-1-ylamino)-4-methylamino-cyclobut-3-ene-1,2-dione)benzeneC48H42N6O9[α]D23=+14.1 (c 1.7, DMSO)Source of chirality: (1R,2S)-indanolAbsolute configuration: (1R,2S)

1,3,5-Tris(3-(1R,2S)-(2-hydroxy-1,2-diphenyl-ethylamino)-4-methylamino-cyclobut-3-ene-1,2-dione)benzeneC63H54N6O9[α]D23=-25.3 (c 3, DMSO)Source of chirality: (1R,2S)-2-hydroxy-1,2-diphenylethylamineAbsolute configuration: (1R,2S)