Enantiodivergent Synthesis of Chiral Tetrahydroquinoxaline Derivatives via Ruthenium-Catalyzed Asymmetric
Zeyu Li1,2, Wenzhe Guo1,2, Wei Hao1,2
1Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing, P. R. China.
Abstract:
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.
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