Enantioselective Rh-catalyzed transfer hydrogenation of α-sulfonyloxy heteroaryl ketones; asymmetric synthesis of (S)-bufuralol

Asymmetric transfer hydrogenation of α-sulfonyloxy heteroaryl ketones mediated by Cp∗RhCl[(S,S)-TsDPEN] using an azeotropic mixture of formic acid/triethylamine afforded the corresponding diol-2-monosulfonates in excellent yield with high enantioselectivity. This led to the asymmetric synthesis of (S)-bufuralol.

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(S)-2-Mesyloxy-1-(2-furanyl)ethanolC7H10O5SEe = 98%[α]D27=-30.7 (c 1.01, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(2-furanyl)ethanolC13H14O5SEe = 99%[α]D27=-25.5 (c 1.63, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Mesyloxy-1-(2-thiophenyl)ethanolC7H10O4S2Ee = 95%[α]D27=-33.2 (c 0.56 CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(2-thiophenyl)ethanolC13H14O4S2Ee = 96%[α]D27=-31.3 (c 1.12, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(2-bezofuranyl)ethanolC17H16O5S[α]D27=-29.0 (c 0.98, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(5-nitrobezofuran-2-yl)ethanolC17H15NO7SEe = 88%[α]D20=-18.0 (c 0.6, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Mesyloxy-1-(5-methoxybezofuran-2-yl)ethanolC12H14O6SEe = 96%[α]D30=-32.0 (c 1.0, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(5-methoxybezofuran-2-yl)ethanolC18H18O6SEe = 96%[α]D27=-23.15 (c 0.97, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(5-bromobezofuran-2-yl)ethanolC17H15BrO5SEe = 94%[α]D20=-18.8 (c 0.91, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Mesyloxy-1-(7-ethylbezofuran-2-yl)ethanolC13H16O5SEe = 97%[α]D20=-45.15 (c 1.11, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(7-ethylbezofuran-2-yl)ethanolC19H20O5SEe = 95%[α]D20=-33.1 (c 0.66, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(7-methoxybezofuran-2-yl)ethanolC18H18O6SEe = 96%[α]D20=-29.6 (c 0.52, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(S)-2-Tosyloxy-1-(2-benzothiophenyl)ethanolC17H16O4S2Ee = 96%[α]D20=-45.0 (c 0.56, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(R)-2-Tosyloxy-1-(3-thiophenyl)ethanolC13H14O4S2Ee = 96%[α]D27=-33.7 (c 1.28, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-2-Tosyloxy-1-(3-benzofuranyl)ethanolC17H16O5SEe = 95%[α]D20=-40.2 (c 0.51, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-2-Tosyloxy-1-(3-benzothiophenyl)ethanolC17H16O4S2Ee = 93%[α]D20=-77.05 (c 0.51, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(S)-BufuralolC16H23NO2Ee = 99%[α]D20=-54.5 (c 0.37, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)