Enantiodivergent Synthesis of Chiral Tetrahydroquinoline Derivatives via Ir-Catalyzed Asymmetric Hydrogenation: Solvent-Dependent Enantioselective Control and Mechanistic Investigations

Abstract

Ir-catalyzed asymmetric hydrogenation of quinolines was developed, and both enantiomers of chiral tetrahydroquinoline derivatives could be easily obtained, respectively, in high yields with good enantioselectivities through the adjustment of reaction solvents (toluene/dioxane: up to 99% yield, 98% ee (R), TON = 680; EtOH: up to 99% yield, 94% ee (S), TON = 1680). It provided an efficient and simple synthetic strategy for the enantiodivergent synthesis of chiral tetrahydroquinolines, and gram-scale asymmetric hydrogenation proceeded well with low-catalyst loading in these two reaction systems. A series of deuterium-labeling experiments, control experiments, and 1H NMR and electrospray ionization-mass spectrometry experiments have been conducted, and a reasonable and possible reaction process was revealed on the basis of these useful observations.

Unveiling a key catalytic pocket for the ruthenium NHC-catalysed asymmetric heteroarene hydrogenation

“…Several homogenous catalysts have been developed for the saturation of heteroarenes by asymmetric hydrogenation 8 and recent examples include complexes of iridium, rhodium, palladium, and ruthenium among other metals bearing a variety of chiral ligands. 9,10 Because of their electron donating properties and structural modularity N-heterocyclic carbenes (NHCs) evolved to be a popular choice for the design of such chiral catalyst complexes. 11 Particularly, the Ru-bis-NHC complex 1-A 10 a ,11 g ,12 has emerged as a privileged catalyst (precursor) that is versatile and powerful in the asymmetric hydrogenation of a broad range of heterocycles including chromones and flavones, 10 b the carbocyclic ring of quinoxalines, 10 a (benzo)furans, 10 c – e (benzo)thiophenes, 10 f indolizines, 10 g 2-pyridones, 10 h cyclic vinylthioethers, 10 i imidazo-pyridines, 10 j 2-oxazolones, 10 k and most recently pyrido-pyrimidones.…”

Cu‐catalyzed Synthesis of Quinolines by Dehydrogenative Reaction of 2‐Aminobenzyl Alcohol and Ketones: A Combined Experimental and Computational Study

“…3‐methyl‐2‐(p–tolyl)quinoline (3 k) [29b] . The general procedure was followed by using 2‐aminobenzyl alcohol (0.5 mmol), 4’‐methyl propiophenone (0.6 mmol), and 2 mol% of Cu(OAc) 2 /BINAP.…”

Cobalt-Catalyzed Asymmetric Dearomative [3 + 2] Annulation of Quinolines, Isoquinolines, and Pyridines

“…For the CADA reaction of quinolines, in addition to the classical catalytic asymmetric hydrogenation, − the well-developed method is the asymmetric Reissert-type reaction − (Scheme a). Due to the resonance stability of quinolines, the electrophilicity of the C2 position is weak, making it difficult to directly undergo nucleophilic dearomatization.…”