Enantiodivergent Synthesis of Chiral Tetrahydroquinoxaline Derivatives via Ruthenium‐Catalyzed Asymmetric Hydrogenation

The enantiodivergent synthesis of R ‐ and S ‐configured tetrahydroquinoxaline derivatives holds significant importance in pharmaceutical and bioorganic chemistry. In this work, we achieved precise control over the R/S selectivity in the ruthenium‐catalyzed asymmetric hydrogenation of 2‐alkyl‐substituted quinoxalines by modulating the catalyst counteranion. Specifically, a chiral diamine–ruthenium complex bearing a BArF counteranion afforded the R ‐configured product. Remarkably, the product chirality was readily inverted by switching to racemic phosphate counteranion. Density functional theory (DFT) calculations identified various weak non‐covalent interactions (such as CH/π and hydrogen bonding) between the counteranion, catalyst, and substrate, revealing the fundamental mechanism of enantioselectivity inversion.