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Catalyst selection based on intermediate stability measured by mass spectrometry

Nature Chemistry volume 2, pages 417–421 (2010)Cite this article

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Abstract

The power of natural selection through survival of the fittest is nature's ultimate tool for the improvement and advancement of species. To apply this concept in catalyst development is attractive and may lead to more rapid discoveries of new catalysts for the synthesis of relevant targets, such as pharmaceuticals. Recent advances in ligand synthesis using combinatorial methods have allowed the generation of a great diversity of catalysts. However, selection methods are few in number. We introduce a new selection method that focuses on the stability of catalytic intermediates measured by mass spectrometry. The stability of the intermediate relates inversely to the reactivity of the catalyst, which forms the basis of a catalyst-screening protocol in which less-abundant species represent the most-active catalysts, ‘the survival of the weakest’. We demonstrate this concept in the palladium-catalysed allylic alkylation reaction using diphosphine and IndolPhos ligands and support our results with high-level density functional theory calculations.

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Figure 1: Catalyst-selection method applied to the palladium-catalysed allylic substitution reaction using diphosphine ligands 1a–1c and 2a–2c.
Figure 2: ‘Survival of the weakest’ method applied in the IndolPhos-Pd catalysed allylic alkylation of rac-diphenylpropenyl acetate.

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Acknowledgements

This work was supported by the National Research School Combination – Catalysis, the European Union (RTN Revcat MRTN-CT-2006–035866) and the Netherlands Organization for Scientific Research (NWO-NCF and NWO-CW). The authors thank S. Ingemann and B. de Bruin for suggestions and discussions.

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Authors and Affiliations

  1. Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, Amsterdam, 1018, WV, The Netherlands

    Jeroen Wassenaar, Eveline Jansen & Joost N. H. Reek

  2. Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling, Scheikundig Laboratorium der Vrije Universiteit, De Boelelaan 1081, Amsterdam, 1081, HV, The Netherlands

    Willem-Jan van Zeist & F. Matthias Bickelhaupt

  3. Department of Crystal & Structural Chemistry, Utrecht University, Padualaan 8, Utrecht, 3584, CH, The Netherlands

    Maxime A. Siegler & Anthony L. Spek

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  1. Jeroen Wassenaar
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Contributions

J.W., E.J. and J.N.H.R. conceived and designed the experiments and analysed the data. W.-J.v.Z. and F.M.B. conceived and designed the DFT calculations and analysed the data. M.A.S. and A.L.S. determined the X-ray crystal structure of 2b. J.W. and E.J. performed the experiments. W.-J.v.Z. performed the DFT calculations. J.W., F.M.B. and J.N.H.R. wrote the paper, and all the authors edited and commented on the manuscript.

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Correspondence to F. Matthias Bickelhaupt or Joost N. H. Reek.

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The authors declare no competing financial interests.

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Crystallographic data for compound 2b (CIF 64 kb)

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Wassenaar, J., Jansen, E., van Zeist, WJ. et al. Catalyst selection based on intermediate stability measured by mass spectrometry. Nature Chem 2, 417–421 (2010). https://doi.org/10.1038/nchem.614

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