Ruthenium Complexes for Asymmetric Hydrogenation and Selective Dehalogenation Revealed via Bayesian Optimization

In this study, we report the discovery of ruthenium complexes that enable efficient asymmetric hydrogenation (AH) of ketones and selective dehalogenation. Using Bayesian optimization-assisted multiparameter screening, we identified ruthenium catalysts exhibiting distinct temperature-dependent behaviors. Below 129 °C, these catalysts achieve AH of aryl ketone halides with up to 99% conversion and >99% enantiomeric excess (ee), without hydrodehalogenation. Above this temperature, catalyst decomposition generates a ruthenium species that selectively promotes base-free dehalogenation using ethanol as a hydrogen donor, achieving yields up to 95%. Unlike conventional hydrodehalogenation catalyzed by metals such as Pd, Ni, or Rh, this method avoids the need for strong bases and hydrogen. These diverse catalytic activities were applied to synthesize the chiral fluoroiodobenzyl alcohol 2C, a key intermediate of Lorlatinib, in 60% yield with 94% ee, and to selectively dechlorinate an Ipragliflozin intermediate with a 64% yield. This work highlights the potential of ruthenium complexes for sustainable and selective catalysis.