Ligand Backbone Influence on the Enantioselectivity in the Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination of Ketones with NH3/H2 Using Binaphthyl‐Substituted Phosphines

The influence of the ligand backbone on the enantioselectivity in the ruthenium‐catalyzed direct asymmetric reductive amination of acetophenone with NH3 and H2, using bidentate binaphthyl‐substituted phosphine ligands, was investigated in a combined computational and experimental study. A model for...

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Bibliographic Details
Published in:ChemCatChem 2022-10, Vol.14 (20), p.n/a
Main Authors: Menche, Maximilian, Klein, Philippe, Hermsen, Marko, Konrath, Robert, Ghosh, Tamal, Wysocki, Jedrzej, Ernst, Martin, Hashmi, A. Stephen K., Schäfer, Ansgar, Comba, Peter, Schaub, Thomas
Format: Article
Language:English
Subjects:
Acetophenone
Ammonia
asymmetric amination
Asymmetry
Atomic properties
computational chemistry
Enantiomers
Ketones
ligand design
Ligands
mechanism
Phosphines
Ruthenium
Substitutes
Substrates
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Summary:The influence of the ligand backbone on the enantioselectivity in the ruthenium‐catalyzed direct asymmetric reductive amination of acetophenone with NH3 and H2, using bidentate binaphthyl‐substituted phosphine ligands, was investigated in a combined computational and experimental study. A model for the bite angle dependence of the enantiomeric excess (ee) when using diphosphines bearing binaphthyl‐groups on the P‐atoms was developed. This revealed a significant potential for increasing the enantioselectivity, if ligands with a larger bite angle than the previously reported (S,S)‐f‐binaphane are used. Suitable backbone candidates were selected from more than one million structures provided by the Cambridge Structural Database (CCDC‐CSD) and the most promising candidates were synthesized accordingly. Despite all efforts, an increase of the ee was not possible with this approach. The larger backbones resulted in the preference of different ligand coordination modes avoiding the formation of the more strongly enantiodiscriminant substrate pocket between the naphthyl wings. Ligand design: The bite angle influence on the enantioselectivity in the ruthenium‐catalyzed direct asymmetric reductive amination of acetophenone with NH3 and H2 using bidentate binaphthyl‐substituted phosphine ligands was investigated in a combined computational and experimental ligand design study. While the investigation reveals a high potential for this approach, it also highlights its challenges.
ISSN:1867-3880
1867-3899
DOI:10.1002/cctc.202200543