Catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl aromatic ketones with diethylzinc

The catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl ketones using diethylzinc as the β-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied to the chemo- and enantioselective reduction of α-methyl/trifluoromethyl diketone, affording 88% yield and 70% ee of the fluorinated hydroxylketone product.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(R)-2,2,2-Trifluoro-1-phenylethanoneC8H7F3O[α]D30.5 = −16.1 (c 0.50, CH2Cl2), 73% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2,2,2-Trifluoro-1-(4-fluorophenyl)ethanolC8H6F4O[α]D29.5 = −16.5 (c 0.50, CH2Cl2), 61% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)-2,2,2-trifluoroethanolC8H6ClF3O[α]D30.6 = −10.8 (c 0.50, CH2Cl2), 60% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2,2,2-Trifluoro-1-p-tolylethanolC9H9F3O[α]D28.5 = −14.7 (c 0.50, CH2Cl2), 61% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2,2,2-Trifluoro-1-(naphthalen-6-yl)ethanolC12H9F3O[α]D29.9 = −11.8 (c 1.00, CH2Cl2), 40% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Chloro-2,2-difluoro-1-phenylethanolC8H7ClF2O[α]D30.1 = −9.1 (c 0.50, CHCl3), 71% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-(2,2,2-Trifluoro-1-hydroxyethyl)phenyl)ethanoneC10H9F3O2[α]D30.2 = −13.1 (c 1.00, CH2Cl2), 70% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)