An oxazaborolidine-based catalytic method for the asymmetric synthesis of chiral allylic alcohols

The enantioselective reduction of a broad range of prochiral α,β-unsaturated ketones 1a–1y using the oxazaborolidine-based catalyst providing chiral allylic alcohols 2a–2y with both high enantioselectivity and chemoselectivity is described. The optimum reaction conditions were found using the oxazaborolidine catalysts prepared in situ from the chiral amino alcohols and borane reagents. Various chiral amino alcohols 4a–4f were screened for this one-pot asymmetric reduction of α,β-enones. Amino alcohol 4a [(R)-DPP] and trimethylboroxine catalyze this asymmetric reduction in toluene at −20 °C within 0.5–2 h in a highly efficient manner. The synthesized chiral allylic alcohols 2a–2y are new compounds, which are valuable intermediates in the preparation of new ligands and in the synthesis of several natural molecules.

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(E)-2-(3-Methylbenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC18H18O91% ee[α]D25 = −38 (c 1.4, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(2-Methylbenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC18H18O90% ee[α]D25 = −46 (c 1.2, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(4-Methoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC18H18O280% ee[α]D25 = −28 (c 1.2, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(2-Methoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC18H18O230% ee[α]D25 = −12 (c 1.4, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(4-Nitrobenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC17H15NO272% ee[α]D25 = +20 (c 1, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-Thiophen-2-ylmethylene-1,2,3,4-tetrahydronaphthalen-1-olC15H14OS68% ee[α]D25 = −11 (c 2.4, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-Furan-2-ylmethylene-1,2,3,4-tetrahydronaphthalen-1-olC15H14O260% ee[α]D25 = −10 (c 3.2, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(5-Methyl-furan-2-ylmethylene)-1,2,3,4-tetrahydronaphthalen-1-olC16H16O282% ee[α]D25 = −5 (c 2.5, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(4-Dimethylaminobenzylidene)-1,2,3,4-tetrahydronaphthalen-1-olC19H21NO50% ee[α]D25 = +27 (c 0.9, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(2-Methoxynaphthalen-1-ylmethylene)-1,2,3,4-tetrahydronaphthalen-1-olC22H20O292% ee[α]D25 = −6 (c 3.3, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-Benzylidene-indan-1-olC16H14O22% ee[α]D25 = +18 (c 0.9, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(3-Methylbenzylidene)-indan-1-olC17H16O30% ee[α]D25 = +32 (c 3.2, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(2-Methylbenzylidene)-indan-1-olC17H16O40% ee[α]D25 = −15 (c 1.5, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(4-Methoxybenzylidene)-indan-1-olC17H16O248% ee[α]D25 = −12 (c 1.4, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-(2-Methoxybenzylidene)-indan-1-olC17H16O226% ee[α]D25 = −4 (c 4.8, CHCl3)Source of chirality: Asymmetric reduction

(E)-2-Furan-2-ylmethylene-indan-1-olC14H12O252% ee[α]D25 = +10 (c 2.9, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-Phenyl-icos-1-en-3-olC26H44O92% ee[α]D25 = +2 (c 3.6, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-o-Tolyl-icos-1-en-3-olC27H46O90% ee[α]D25 = +5 (c 3.6, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-(4-Methoxy-phenyl)-icos-1-en-3-olC27H46O294% ee[α]D25 = +2 (c 2.7, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-(2-Methoxy-phenyl)-icos-1-en-3-olC27H46O272% ee[α]D25 = +3 (c 3.9, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-Furan-2-yl-icos-1-en-3-olC24H42O264% ee[α]D25 = −3 (c 4.5, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-(4-Dimethylaminophenyl)-icos-1-en-3-olC28H49NO92% ee[α]D25 = +28 (c 4.5, CHCl3)Source of chirality: Asymmetric reduction

(E)-1-Thiophen-2-yl-icos-1-en-3-olC24H42OS82% ee[α]D25 = +5 (c 2.5, CHCl3)Source of chirality: Asymmetric reduction