Rigid P-Chiral Phosphine Ligands with tert-Butylmethylphosphino Groups for Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Alkenes

Both enantiomers of 2,3-bis­(tert-butylmethylphosphino)­quinoxaline (QuinoxP*), 1,2-bis­(tert-butylmethylphosphino)­benzene (BenzP*), and 1,2-bis­(tert-butylmethylphosphino)-4,5-(methylenedioxy)­benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine–boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl α-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.

以对映纯的(S)-和(R)-叔丁基甲基膦硼烷加合物为关键中间体，通过简短合成步骤制备了2,3-双(叔丁基甲基膦基)喹喔啉(QuinoxP*)、1,2-双(叔丁基甲基膦基)苯(BenzP*)以及1,2-双(叔丁基甲基膦基)-4,5-(亚甲二氧基)苯(DioxyBenzP*)的两种对映异构体。所有此类配体均为结晶固体，暴露于空气中不易被氧化。其铑配合物在脱氢氨基酸衍生物、烯酰胺等官能化烯烃的不对称氢化反应中表现出优异的对映选择性与极高的催化活性。通过高效制备数种含氨基酸或二级胺结构单元的手性药物活性成分，证实了这类催化剂的实用价值。采用结构简单的配体BenzP*的铑配合物开展不对称氢化反应的机理研究，以α-乙酰氨基肉桂酸甲酯作为标准模型底物，结合低温核磁共振(NMR)研究与密度泛函理论(DFT)计算，揭示了该反应路径与对映选择性机制的全新认知。