American Chemical Society
ja209700j_si_001.cif (29.06 kB)

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

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posted on 2012-01-25, 00:00 authored by Tsuneo Imamoto, Ken Tamura, Zhenfeng Zhang, Yumi Horiuchi, Masashi Sugiya, Kazuhiro Yoshida, Akira Yanagisawa, Ilya D. Gridnev
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.