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

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 H-1 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.

Automated summary

The study developed an efficient and simple synthetic strategy for obtaining both enantiomers of chiral tetrahydroquinoline derivatives through the adjustment of reaction solvents. Gram-scale asymmetric hydrogenation proceeded well with low-catalyst loading, and a possible reaction process was revealed based on various experiments conducted.