Selective Asymmetric Transfer Hydrogenation of α‐Substituted Acetophenones with Bifunctional Oxo‐Tethered Ruthenium(II) Catalysts

Abstract

Abstract A practical method for the asymmetric transfer hydrogenation of α‐substituted ketones was developed utilizing oxo‐tethered N ‐sulfonyldiamine‐ruthenium complexes. Reduction by HCO 2 H and HCO 2 K in a mixed solvent of EtOAc/H 2 O allowed for the selective synthesis of halohydrins from 2‐bromoacetophenone (98%) and 2‐chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO 2 H and Et 3 N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α‐sulfonated ketones without eroding the leaving group. magnified image