Homogeneous Chiral Nickel-Catalyzed Asymmetric Hydrogenation of Substituted Aromatic α-Amiooketone Hydrochlorides through Dynamic Kinetic Resolution

摘要

Precious transition metals, such as rhodium, iridium, and ruthenium, play a crucial role in homogeneous catalysis of asymmetric hydrogenation. However, they are expensive rare metals and are anticipated to be limited by the depletion of natural resources in the future. Hence, the investigation and development of sustainable methods using abundant and cheap base transition metals is desirable. Recently, we have developed of homogeneous chiral nickel catalysts for the asymmetric hydrogenation of a chiral, labile α-amino-β-keto esters through dynamic kinetic resolution (DKR). Asymmetric hydrogenation through DKR constitutes one of the most important carbon-hydrogen bond forming reactions, in which racemic substrates can be converted into enantiomerically pure products with two or more contiguous stereogenic centers using a single op-eration. As an extension of this study, we have investigated the diastereoselective hydrogenation of substituted aromatic α-aminoketone hydrochlorides by using a homogeneous achi-rai nickel catalyst. During the course of this study, we discovered a novel asymmetric hydrogenation and a remarkable selectivity change, based on the solvent effect. We now describe the asymmetric hydrogenation of substituted aromatic a-aminoketone hydrochlorides through DKR to afford β-aminoalco-hols, which are important medicines and chiral modifiers, with anti stereochemistry and high enantio- and diasteroselec-tivity. Although the enantioselective hydrogenation of a-ami-noketones has been extensively investigated, studies concerning the diastereoselective hydrogenation of substituted aromatic primary a-aminoketones are still limited.