Asymmetric transfer hydrogenation of 2-tosyloxy-1-(4-hydroxyphenyl)ethanone derivatives: synthesis of (R)-tembamide, (R)-aegeline, (R)-octopamine, and (R)-denopamine

Catalytic transfer hydrogenation of 2-tosyloxy-1-(4-hydroxyphenyl)ethanone derivatives leads to efficient synthesis of β-adrenergic agonists, (R)-tembamide, (R)-aegeline, (R)-octopamine, and (R)-denopamine.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(R)-1-(4-Methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanolC16H18O5SEe = 94%[α]D25=-50.7 (c 0.79, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-1-(4-Benzyloxyphenyl)-2-(p-tolylsulfonyloxy)ethanolC22H22O5SEe = 95%[α]D25=-42.5 (c 0.79, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-2-Azido-1-(p-methoxyphenyl)ethanolC9H11N3O2[α]D25=-86.1 (c 1.39, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-2-Amino-1-(p-methoxyphenyl)ethanolC9H13NO2[α]D25=-38.3 (c 0.49, EtOH)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-TembamideC16H17NO3[α]D25=-59.4 (c 0.57, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-AegelineC18H19NO3[α]D25=-49.1 (c 0.27, MeOH)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-(−)-2-Azido-1-(p-benzyloxyphenyl)ethanolC15H15N3O2[α]D25=-70.3 (c 1.09, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-OctopamineC8H11NO2[α]D25=-37.3 (c 1.02, H2O)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-1-(p-Benzyloxyphenyl)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethanolC25H29NO4[α]D25=-19.2 (c 1.1, MeOH)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)

(R)-DenopamineC18H23NO4[α]D25=-27.7 (c 0.91, MeOH)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (R)