title: Highly enantioselective hydrogenation of quinolines using phosphine-free chiral cationic ruthenium catalysts: scope, mechanism, and origin of enantioselectivity.
abstract: Asymmetric hydrogenation of quinolines catalyzed by chiral cationic η(6)-arene-N-tosylethylenediamine-Ru(II) complexes have been investigated. A wide range of quinoline derivatives, including 2-alkylquinolines, 2-arylquinolines, and 2-functionalized and 2,3-disubstituted quinoline derivatives, were efficiently hydrogenated to give 1,2,3,4-tetrahydroquinolines with up to >99% ee and full conversions. This catalytic protocol is applicable to the gram-scale synthesis of some biologically active tetrahydroquinolines, such as (-)-angustureine, and 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, a key intermediate for the preparation of the antibacterial agent (S)-flumequine. The catalytic pathway of this reaction has been investigated in detail using a combination of stoichiometric reaction, intermediate characterization, and isotope labeling patterns. The evidence obtained from these experiments revealed that quinoline is reduced via an ionic and cascade reaction pathway, including 1,4-hydride addition, isomerization, and 1,2-hydride addition, and hydrogen addition undergoes a stepwise H(+)/H(-) transfer process outside the coordination sphere rather than a concerted mechanism. In addition, DFT calculations indicate that the enantioselectivity originates from the CH/π attraction between the η(6)-arene ligand in the Ru-complex and the fused phenyl ring of dihydroquinoline via a 10-membered ring transition state with the participation of TfO(-) anion.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Institute of Chemistry and Graduate School, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China.
authors.forename: Tianli
authors.initials: T
authors.lastname: Wang
authors.forename: Lian-Gang
authors.initials: LG
authors.lastname: Zhuo
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Ding
authors.forename: Yanmei
authors.initials: Y
authors.lastname: He
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Fan
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Yu
authors.forename: Albert S C
authors.initials: AS
authors.lastname: Chan
mesh_terms: D002384:Catalysis; D006865:Hydrogenation; D011804:Quinolines / Q000737:chemistry*; D012428:Ruthenium; D013237:Stereoisomerism
chemical_list: D011804:Quinolines; D012428:Ruthenium