Additive effects of amines on asymmetric hydrogenation of quinoxalines catalyzed by chiral iridium complexes

Takuto Nagano, Atsuhiro Iimuro, Rino Schwenk, Takashi Ohshima, Yusuke Kita, Antonio Togni, Kazushi Mashima

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The additive effects of amines were realized in the asymmetric hydrogenation of 2-phenylquinoxaline, and its derivatives, catalyzed by chiral cationic dinuclear triply halide-bridged iridium complexes [{Ir(H)[diphosphine]} 2(μ-X)3]X (diphosphine=(S)-2,2'-bis(diphenylphosphino)- 1,1'-binaphthyl [(S)-BINAP], (S)-5,5'-bis(diphenylphosphino)-4,4'-bi-1,3- benzodioxole [(S)-SEGPHOS], (S)-5,5'-bis(diphenylphosphino)-2,2,2',2'- tetrafluoro-4,4'-bi-1,3-benzodioxole [(S)-DIFLUORPHOS]; X=Cl, Br, I) to produce the corresponding 2-aryl-1,2,3,4-tetrahydroquinoxalines. The additive effects of amines were investigated by solution dynamics studies of iridium complexes in the presence of N-methyl-p-anisidine (MPA), which was determined to be the best amine additive for achievement of a high enantioselectivity of (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline, and by labeling experiments, which revealed a plausible mechanism comprised of two cycles. One catalytic cycle was less active and less enantioselective; it involved the substrate-coordinated mononuclear complex [IrHCl2(2-phenylquinoxaline){(S)-BINAP}], which afforded half-reduced product 3-phenyl-1,2-dihydroquinoxaline. A poorly enantioselective disproportionation of this half-reduced product afforded (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline. The other cycle involved a more active hydride-amide catalyst, derived from amine-coordinated mononuclear complex [IrCl2H(MPA){(S)-BINAP}], which functioned to reduce 2-phenylquinoxaline to (S)-2-phenyl-1,2,3,4-tetrahydroquinoxaline with high enantioselectivity. Based on the proposed mechanism, an IrI-JOSIPHOS (JOSIPHOS=(R)-1-[(Sp)-2-(dicyclohexylphosphino)ferrocenylethyl] diphenylphosphine) catalyst in the presence of amine additive resulted in the highest enantioselectivity for the asymmetric hydrogenation of 2-phenylquinoxaline. Interestingly, the reaction rate and enantioselectivity were gradually increased during the reaction by a positive-feedback effect from the product amines.

Original languageEnglish
Pages (from-to)11578-11592
Number of pages15
JournalChemistry - A European Journal
Issue number37
Publication statusPublished - Sept 10 2012

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry


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