Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Matters Arising
  • Published:

Revisiting the amine-catalysed cross-coupling

Nature Catalysis volume 4, pages 991–993 (2021)Cite this article

Subjects

The Original Article was published on 18 January 2021

arising from L. Xu et al. Nature Catalysis https://doi.org/10.1038/s41929-020-00564-z (2021).

Very recently, it was demonstrated that special amine molecules are able to catalyse the Suzuki–Miyaura coupling reaction. Here we show that in this recent transformation homeopathic palladium impurities and trace phosphorous species are present. These originate from the conditions used for the organocatalyst synthesis and are responsible for the catalytic effect instead of the amine species. This finding confirms the power of palladium in cross-coupling and draws attention to the impurity effect in this field of chemical research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Mechanistic studies of the amine-catalysed Suzuki–Miyaura coupling.

Data availability

The authors declare that the main data supporting the findings of this study are available within the article and its Supplementary Information or from the corresponding authors upon request. Source data are provided with this paper.

References

  1. Miyaura, N. & Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 95, 2457–2483 (1995).

    Article  CAS  Google Scholar 

  2. Hudson, R. & Katz, J. L. Toward the selection of sustainable catalysts for Suzuki–Miyaura coupling: a gate-to-gate analysis. ACS Sustain. Chem. Eng. 6, 14880–14887 (2018).

    Article  CAS  Google Scholar 

  3. Brown, D. G. & Boström, J. Analysis of past and present synthetic methodologies on medicinal chemistry: where have all the new reactions gone? J. Med. Chem. 59, 4443–4458 (2015).

    Article  Google Scholar 

  4. Xu, L. et al. The amine-catalysed Suzuki–Miyaura-type coupling of aryl halides and arylboronic acids. Nat. Catal. https://doi.org/10.1038/s41929-020-00564-z (2021).

  5. Arvela, R. K. et al. A reassessment of the transition-metal free Suzuki-type coupling methodology. J. Org. Chem. 70, 161–168 (2005).

    Article  CAS  Google Scholar 

  6. Buchwald, S. L. & Bolm, C. On the role of metal contaminants in catalyses with FeCl3. Angew. Chem. Int. Ed. 48, 5586–5587 (2009).

    Article  CAS  Google Scholar 

  7. Lauterbach, T., Livendahl, M., Rosellon, A., Espinet, P. & Echavarren, A. M. Unlikeliness of Pd-free gold(I)-catalyzed Sonogashira coupling reactions. Org. Lett. 12, 3006–3009 (2010).

    Article  CAS  Google Scholar 

  8. Gonda, Z., Tolnai, G. L. & Novák, Z. Dramatic impact of ppb levels of palladium on the ‘copper-catalyzed’ Sonogashira coupling. Chem. Eur. J. 16, 11822–11826 (2010).

    Article  CAS  Google Scholar 

  9. Leadbeater, N. E. When is free really free? Nat. Chem. 2, 1007–1009 (2010).

    Article  CAS  Google Scholar 

  10. Pentsak, E. O., Eremin, D. B., Gordeev, E. G. & Ananikov, V. P. Phantom reactivity in organic and catalytic reactions as a consequence of microscale destruction and contamination-trapping effects of magnetic stir bars. ACS Catal. 9, 3070–3081 (2019).

    Article  CAS  Google Scholar 

  11. French, J. M., Griffiths, J. R. & Diver, S. T. Removal of palladium from cross-coupling reactions using isocyanide reagents. Adv. Synth. Catal. 357, 361–365 (2015).

    Article  CAS  Google Scholar 

  12. Magano, J. & Dunetz, J. R. Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals. Chem. Rev. 111, 2177–2250 (2011).

    Article  CAS  Google Scholar 

  13. Carroll, M. A. & Wood, R. A. Arylation of anilines: formation of diarylamines using diaryliodonium salts. Tetrahedron 63, 11349–11354 (2007).

    Article  CAS  Google Scholar 

  14. Song, F. L., Garner, A. L. & Koide, K. A highly sensitive fluorescent sensor for palladium based on the allylic oxidative insertion mechanism. J. Am. Chem. Soc. 129, 12354–12355 (2007).

    Article  CAS  Google Scholar 

  15. Bu, X., Koide, K., Carder, E. J. & Welch, C. J. Rapid analysis of residual palladium in pharmaceutical development using a catalysis-based fluorometric method. Org. Process Res. Dev. 17, 108–113 (2012).

    Article  Google Scholar 

Download references

Acknowledgements

We thank the support of the National Research, Development and Innovation Office (NKFIH K132077, Pd124592 and KH130048). G.L.T. is grateful for a János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/536/20) and the UNKP-20-5 grant. B.V. is grateful for the support of the UNKP-20-3 grant. This work was completed in the ELTE Institutional Excellence Program supported by the National Research, Development and Innovation Office (NKFIH- TKP2020-IKA-05). The theoretical work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2033 – 390677874 – RESOLV. We thank K. Hegedüs at the Research Centre for Natural Sciences, Budapest, for assistance with the NMR measurements, and for Z. Czégény (Research Centre for Natural Sciences, Budapest) for the read through of the manuscript. We thank B. M. Stoltz and T. J. Fulton at Caltech for proofreading the manuscript.

Author information

Author notes

  1. János Daru

    Present address: Daru Research Group, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary

Authors and Affiliations

  1. ELTE “Lendület” Catalysis and Organic Synthesis Research Group, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary

    Zoltán Novák, Réka Adamik, János T. Csenki, Ferenc Béke, Regina Gavaldik, Bálint Varga & Bálint Nagy

  2. Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, Hungary

    Zoltán May

  3. Lehrstuhl für Theoretische Chemie, Ruhr–Universität Bochum, Bochum, Germany

    János Daru

  4. ELTE Tolnai Research Group, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary

    Zsombor Gonda & Gergely L. Tolnai

Authors
  1. Zoltán Novák
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Réka Adamik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. János T. Csenki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ferenc Béke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Regina Gavaldik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bálint Varga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bálint Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zoltán May
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. János Daru
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zsombor Gonda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gergely L. Tolnai
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.L.T., Z.N., Z.M., J.D. and F.B. took part in the composition of manuscript. G.L.T., Z.N. and Z.G. directed the research. R.A., F.B., J.T.C., R.G., B.V. and Z.G. performed the experiments. Z.M. performed the ICP analyses. J.D. performed the density functional theory studies. All the authors participated in the final composition of the manuscript.

Corresponding authors

Correspondence to Zoltán Novák, Zoltán May, János Daru, Zsombor Gonda or Gergely L. Tolnai.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Nicholas Leadbeater and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–7, Notes 1–6, Discussion and references.

Source data

Source Data Fig. 1

Statistical source data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novák, Z., Adamik, R., Csenki, J.T. et al. Revisiting the amine-catalysed cross-coupling. Nat Catal 4, 991–993 (2021). https://doi.org/10.1038/s41929-021-00709-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-021-00709-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing