Enantioselective reduction of benzofuryl halomethyl ketones: asymmetric synthesis of (R)-bufuralol

Enantioselective reduction of representative 2-(bromoacetyl)- and 2-(chloroacetyl)benzofurans with (−)-B-chlorodiisopinocampheylborane and by transfer hydrogenation with formic acid/triethylamine in the presence of RhCl[R,R-TsDPEN](C5Me5) is described. Transfer hydrogenation of the chloro ketones produced the corresponding chlorohydrins of ⩾95% ee. (R)-Bufuralol of 96% ee was prepared from the corresponding chloro ketone by transfer hydrogenation–substitution.

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1-(Benzofuran-2-yl)-2-chloroethanolC10H9ClO2Ee = 97%[α]D25=+27.7 (c 3.60, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

1-(Benzofuran-2-yl)-2-bromoethanolC10H9BrO2Ee = 91%[α]D20=+15.9 (c 5.03, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Bromo-1-(3-methylbenzofuran-2-yl)ethanolC11H11BrO2Ee = 94%[α]D20=+44.6 (c 3.92, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Chloro-1-(3-methylbenzofuran-2-yl)ethanolC11H11ClO2Ee = 97%[α]D20=+12.4 (c 3.22, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Chloro-1-(7-ethylbenzofuran-2-yl)ethanolC12H13ClO2Ee = 98%[α]D25=+29.6 (c 5.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Chloro-1-(3,5-dimethylbenzofuran-2-yl)ethanolC12H13ClO2Ee = 98%[α]D25=+17.1 (c 5.26, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Chloro-1-(3,7-dimethylbenzofuran-2-yl)ethanolC12H13ClO2Ee = 96%[α]D25=+8.1 (c 4.91, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S

2-Chloro-1-(5-ethyl-3-methylbenzofuran-2-yl)ethanolC13H15ClO2Ee = 97%[α]D25=+9.4 (c 5.30, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S