Asymmetric synthesis of β-amino alcohols by the transfer hydrogenation of α-keto imines

The asymmetric transfer hydrogenation of representative aryl and benzofuranyl 2-tert-butylaminoethanones with formic acid–triethylamine, catalyzed by RhCl[(R,R)-TsDPEN](C5Me5), produced the corresponding β-tert-butylamino alcohols in 97–99% ee. A short asymmetric synthesis of (R)-bufuralol, a potent β-adrenergic receptor antagonist, is described. This approach to β-amino alcohols from ketones circumvents the halogenation–reduction–amination sequence.

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2-tert-Butylamino-1-(4-chlorophenyl)-ethanolC12H18ClNOEe = 97%[α]D20=+66.6 (c 2.06, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

1-(4-Bromophenyl)-2-(tert-butylamino)ethanolC12H18BrNOEe = 98%[α]D20=+65.9 (c 2.05, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

1-(Benzofuran-2-yl)-2-(tert-butylamino)ethanolC14H19NO2Ee = 98%[α]D23=+37.6 (c 2.10, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

2-(tert-Butylamino)-1-(7-ethylbenzofuran-2-yl)ethanolC16H23NO2Ee = 98%[α]D20=+27.2 (c 1.93, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (R)