Asymmetric Transfer Hydrogenation of ω -Bromo Acetophenones in Aqueous Media

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Optical active ω-bromophenylethanols are useful building blocks for synthesis of various pharmaceuticals such as α 1-, β 2-, and β 3- adrenergic receptor agonists, which are always obtained though a biotransformative pathway and using boron reagent with rigorous conditions [1]. To our knowledge, the metal-catalysed transfer hydrogenation is seldom applied in this reaction. Recently we have developed a water-soluble chiral Ru-complex and applied successfully in transfer hydrogenation of ω-bromo acetophenones in aqueous media [2], which can not be performed in homogeneous system with HCOOH/NEt3 as hydrogen donor[3] .In this paper, we will report that asymmetric transfer hydrogenation of ω-bromo acetophenones was successfully performed in aqueous media by employing hydrophobic Rh-amido complex (TsDPEN-Rh) as catalyst and HCOONa as hydrogen donor. Moreover, marked increasing of activity and high enantioselectivity (up to 98%) of ω-bromo acetophenone 1a was found in the presence of different micelles or vesicles. This method was also applied successfully in preparation of the important chiral medicinal intermediates, such as the precursor of salbutamol, 2b and fermoterol, 2c with high enantioselectivity.
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