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.

Iron/Brønsted Acid Catalyzed Asymmetric Hydrogenation: Mechanism and Selectivity‐Determining Interactions

“…These interactions are often of noncovalent character, including repulsive forces (sterics) but also attractive forces such as C-H/π dispersion type interactions, which are increasingly recognized as selectivity-determining factors (for a recent review on this topic see also [26]). [27,28,29,30] Different iron-catalyzed hydrogenation reactions have been studied computationally, [31,32] inluding the symmetric ironcyclopentadienone-catalysed hydrogenation of acyclic imines [ 33,34 ] and ketones . [ 35 , 36 ] However, to our knowledge a similar analysis for iron-cyclopentadienone-catalysed hydrogenation in presence of a Brønsted acid has not yet been performed.…”

Metal‐Free Hydrogen Atom Transfer from Water: Expeditious Hydrogenation of N‐Heterocycles Mediated by Diboronic Acid

“…Quinoxaline and acridine derivatives gave comparable results to quinoline derivatives with good to excellent yields for most cases. Quite interestingly, 1,10‐phenanthroline gave the selective hydrogenation product 2 ab , which was isolated with a yield of 69 %.This might be attributed to the autoxidative dehydrogenation of the final reduction product under air . It was noted that benzothiazole derivatives are quite stable and usually employed as ligands in the transition‐metal catalyzed hydrogenation .…”

Solvent‐Regulated Asymmetric Hydrogenation of Quinoline Derivatives in Oligo(Ethylene Glycol)s through Host–Guest Interactions

“…Other commercially available reagents were purchased from Alfa Aeser and Aldrich and used as received without further purification. All of the ruthenium catalysts were synthesized according to a literature procedure . 1 H and 13 C NMR spectra were recorded at ambient temperature in CDCl 3 on a Bruker Model Advance DMX 300 Spectrometer ( 1 H: 300 MHz; 13 C: 75 MHz) with tetramethylsilane (TMS) as an internal standard.…”