Additive Effects of Amines on Asymmetric Hydrogenation of Quinoxalines Catalyzed by Chiral Iridium Complexes

• Published in: Chemistry : a European journal Vol. 18; no. 37; pp. 11578 - 11592
• Main Authors: Nagano, Takuto, Iimuro, Atsuhiro, Schwenk, Rino, Ohshima, Takashi, Kita, Yusuke, Togni, Antonio, Mashima, Kazushi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 10.09.2012; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Additives; Amines; Amines - chemical synthesis; Amines - chemistry; asymmetric catalysis; Asymmetry; Catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; Derivatives; Hydrogenation; iridium; Iridium - chemistry; Iridium compounds; Molecular Structure; nitrogen heterocycles; Organometallic Compounds - chemistry; Physical Sciences; Quinoxalines; Quinoxalines - chemistry; reaction mechanisms; Science & Technology; PYRIDINE-DERIVATIVES; reaction mechanisms; asymmetric catalysis; hydrogenation; HETEROAROMATIC-COMPOUNDS; AUTOCATALYTIC REACTION; iridium; HOMOGENEOUS HYDROGENATION; HIGHLY ENANTIOSELECTIVE HYDROGENATION; DIPHOSPHINE LIGANDS; nitrogen heterocycles; QUINOLINE DERIVATIVES; BISPHOSPHINE LIGANDS; ORGANOCATALYTIC TRANSFER HYDROGENATION; IMINE HYDROGENATION
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201201366

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. Additive effects were investigated in the asymmetric hydrogenation of 2‐substituted quinoxalines catalyzed by a chiral iridium complex (see scheme). Catalytic activity and enantioselectivity were improved by the addition of an aniline derivatives and product amine.