Chiral spiroaminoborate ester as a highly enantioselective and efficient catalyst for the borane reduction of furyl, thiophene, chroman, and thiochroman-containing ketones

Prochiral heteroaryl ketones containing furan, thiophene, chroman, and thiochroman moieties were successfully reduced in the presence of 1–10 mol % of spiroaminoborate ester 1 with different borane sources to afford non-racemic alcohols in up to 99% ee. In addition, modest enantioselectivity, around 80% ee, was achieved in the reduction of linear α,β-unsaturated heteroaryl ketones.

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Chroman-4-olC9H10O2Ee >99.8%[α]D20=+61 (c 0.04, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1(Thiophen-2-yl)ethanolC6H8OSEe = 98%[α]D23=+26 (c 2.0, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

1-(5-Chloro-thiophen-2-yl)-ethanolC6H7ClOSEe = 98%[α]D23=+27.4 (c 1.5, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(Thiophen-3-yl)ethanolC6H8OSEe = 98.4%[α]D23=+27 (c 1.5, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(2,5-Dimethylthiophen-3-yl)ethanolC8H12OSEe = 95.6%[α]D23=+18 (c 3.5, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(2,5-Dichlorothiophen-3-yl)ethanolC6H6Cl2OSEe = 99.8%[α]D20=+30 (c 0.011, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-Thiochroman-4-olC9H10OSEe = 98.7%[α]D23=+134 (c 1.9, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-6-Chlorothiochroman-4-olC9H9ClOSEe = 98.7%[α]D23=+79 (c 1.9, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-4,5,6,7-Tetrahydrobenzo[b]thiophen-4-olC8H10OSEe = 94%[α]D23=-7 (c 1.0, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R,E)-4-Phenylbut-3-3n-2-olC10H12OEe = 80%[α]D23=+25 (c 4, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R,Z)-4-(Furan-2-yl)but-3-en-2-olC8H10O2Ee = 83%[α]D23=+24 (c 2.5, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R,E)-4-(Thiophen-2-yl)but-3-en-2-olC8H10OSEe = 80%[α]D23=+18.2 (c 2.3, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

2,3-Dihydro-benzofuran-3-olC8H8O2Ee = 92%[α]D23=+61 (c 1.8, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(Furan-2-yl)-ethanolC6H8O2Ee = 95%[α]D23=+21 (c 1.45, CHCl3)Bp: 150 °C/1mmHgSource of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(5-Methylfuran-2-yl)-ethanolC7H10O2Ee = 91%[α]D23=+7.2 (c 1.25, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)

(R)-1-(Benzofuran-2-yl)-ethanolC10H10O2Ee = 96%[α]D23=+18 (c 3, CHCl3)Source of chirality: (S)-2-[(1,3,2-dioxaborolan-2-yloxy)diphenylmethyl]pyrrolidineAbsolute configuration: (R)