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.

  • Article
  • Published:

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

Nature Chemistry volume 9, pages 779–784 (2017)Cite this article

Subjects

Abstract

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

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

Figure 1: Design of new ligands for Ni catalysis enables Suzuki coupling of benzylic acetals.
Figure 2: Ligand evaluation and timepoint studies.
Figure 3: Steric parameterization and analysis.

Similar content being viewed by others

References

  1. Johansson Seechurn, C. C. C., Kitching, M. O., Colacot, T. J. & Snieckus, V. Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 nobel prize. Angew. Chem. Int. Ed. 51, 5062–5085 (2012).

    Article  CAS  Google Scholar 

  2. Martin, R. & Buchwald, S. L. Palladium-catalyzed Suzuki–Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res. 41, 1461–1473 (2008).

    Article  CAS  Google Scholar 

  3. Fu, G. C. The development of versatile methods for palladium-catalyzed coupling reactions of aryl electrophiles through the use of P(t-Bu)3 and PCy3 as ligands. Acc. Chem. Res. 41, 1555–1564 (2008).

    Article  CAS  Google Scholar 

  4. Marion, N. & Nolan, S. P. Well-defined N-heterocyclic carbenes–palladium(II) precatalysts for cross-coupling reactions. Acc. Chem. Res. 41, 1440–1449 (2008).

    Article  CAS  Google Scholar 

  5. Tasker, S. Z., Standley, E. A. & Jamison, T. F. Recent advances in homogeneous nickel catalysis. Nature 509, 299–309 (2014).

    Article  CAS  Google Scholar 

  6. Zultanski, S. L. & Fu, G. C. Catalytic asymmetric γ-alkylation of carbonyl compounds via stereoconvergent Suzuki cross-couplings. J. Am. Chem. Soc. 133, 15362–15364 (2011).

    Article  CAS  Google Scholar 

  7. Tobisu, M., Yasutome, A., Kinuta, H., Nakamura, K. & Chatani, N. 1,3-Dicyclohexylimidazol-2-ylidene as a superior ligand for the nickel-catalyzed cross-couplings of aryl and benzyl methyl ethers with organoboron reagents. Org. Lett. 16, 5572–5575 (2014).

    Article  CAS  Google Scholar 

  8. Lavoie, C. M. et al. Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design. Nat. Commun. 7, 11073 (2016).

    Article  Google Scholar 

  9. Hansen, E. C. et al. New ligands for nickel catalysis from diverse pharmaceutical heterocycle libraries. Nat. Chem. 8, 1126–1130 (2016).

    Article  CAS  Google Scholar 

  10. Nielsen, D. K. & Doyle, A. G. Nickel-catalyzed cross-coupling of styrenyl epoxides with boronic acids. Angew. Chem. Int. Ed. 50, 6056–6059 (2011).

    Article  CAS  Google Scholar 

  11. Hie, L. et al. Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds. Nature 524, 79–83 (2015).

    Article  CAS  Google Scholar 

  12. Cao, X. et al. Nickel-catalyzed arylation of heteroaryl-containing diarylmethanes: exceptional reactivity of the Ni(NIXANTPHOS)-based catalyst. Chem. Sci. 7, 611–618 (2016).

    Article  CAS  Google Scholar 

  13. Harper, K. C. & Sigman, M. S. Three-dimensional correlation of steric and electronic free energy relationships guides asymmetric propargylation. Science 333, 1875–1878 (2011).

    Article  CAS  Google Scholar 

  14. Milo, A., Bess, E. N. & Sigman, M. S. Interrogating selectivity in catalysis using molecular vibrations. Nature 507, 210–214 (2014).

    Article  CAS  Google Scholar 

  15. Tolman, C. A. Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis. Chem. Rev. 77, 313–348 (1977).

    Article  CAS  Google Scholar 

  16. Clavier, H. & Nolan, S. P. Percent buried volume for phosphine and N-heterocyclic carbene ligands: steric properties in organometallic chemistry. Chem. Commun. 46, 841–861 (2010).

    Article  CAS  Google Scholar 

  17. Rosen, B. M. et al. Nickel-catalyzed cross-couplings involving carbon–oxygen bonds. Chem. Rev. 111, 1346–1416 (2011).

    Article  CAS  Google Scholar 

  18. Graham, T. J. A., Shields, J. D. & Doyle, A. G. Transition metal-catalyzed cross coupling with N-acyliminium ions derived from quinolines and isoquinolines. Chem. Sci. 2, 980–984 (2011).

    Article  CAS  Google Scholar 

  19. Graham, T. J. A. & Doyle, A. G. Nickel-catalyzed cross-coupling of chromene acetals and boronic acids. Org. Lett. 14, 1616–1619 (2012).

    Article  CAS  Google Scholar 

  20. Sylvester, K. T., Wu, K. & Doyle, A. G. Mechanistic investigation of the nickel-catalyzed Suzuki reaction of N,O-acetals: evidence for boronic acid assisted oxidative addition and an iminium activation pathway. J. Am. Chem. Soc. 134, 16967–16970 (2012).

    Article  CAS  Google Scholar 

  21. Shields, J. D., Ahneman, D. T. & Doyle, A. G. Enantioselective, nickel-catalyzed Suzuki cross-coupling of quinolinium ions. Org. Lett. 16, 142–145 (2014).

    Article  CAS  Google Scholar 

  22. Ameen, D. & Snape, T. J. Chiral 1,1-diaryl compounds as important pharmacophores. Med. Chem. Commun. 4, 893–907 (2013).

    Article  CAS  Google Scholar 

  23. Suresh, C. H. & Koga, N. Quantifying the electronic effect of substituted phosphine ligands via molecular electrostatic potential. Inorg. Chem. 41, 1573–1578 (2002).

    Article  CAS  Google Scholar 

  24. Hartwig, J. F. Organotransition Metal Chemistry: From Bonding to Catalysis (University Science, 2010).

    Google Scholar 

  25. Poater, A. et al. Sambvca: a Web application for the calculation of the buried volume of N-heterocyclic carbene ligands. Eur. J. Inorg. Chem. 2009, 1759–1766 (2009).

    Article  Google Scholar 

  26. Barder, T. E., Walker, S. D., Martinelli, J. R. & Buchwald, S. L. Catalysts for Suzuki–Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 127, 4685–4696 (2005).

    Article  CAS  Google Scholar 

  27. Taylor, B. L. H., Harris, M. R. & Jarvo, E. R. Synthesis of enantioenriched triarylmethanes by stereospecific cross-coupling reactions. Angew. Chem. Int. Ed. 51, 7790–7793 (2012).

    Article  CAS  Google Scholar 

  28. Guan, B.-T. et al. Direct benzylic alkylation via Ni-catalyzed selective benzylic sp3 C−O activation. J. Am. Chem. Soc. 130, 3268–3269 (2008).

    Article  CAS  Google Scholar 

  29. Eildal, J. N. N. et al. From the selective serotonin transporter inhibitor citalopram to the selective norepinephrine transporter inhibitor talopram: synthesis and structure–activity relationship studies. J. Med. Chem. 51, 3045–3048 (2008).

    Article  CAS  Google Scholar 

  30. Greene, M. A., Yonova, I. M., Williams, F. J. & Jarvo, E. R. Traceless directing group for stereospecific nickel-catalyzed alkyl–alkyl cross-coupling reactions. Org. Lett. 14, 4293–4296 (2012).

    Article  CAS  Google Scholar 

  31. Tollefson, E. J., Hanna, L. E. & Jarvo, E. R. Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and esters. Acc. Chem. Res. 48, 2344–2353 (2015).

    Article  CAS  Google Scholar 

  32. Williamson, A. XLV. Theory of ætherification. Philos. Mag. Series 3 37, 350–356 (1850).

    Google Scholar 

  33. Fuson, R. C. & Jackson, H. L. A comparison of certain dimesitylmethyl derivatives with the corresponding triarylmethyl compounds. J. Am. Chem. Soc. 72, 351–353 (1950).

    Article  CAS  Google Scholar 

  34. Arendt, K. M. & Doyle, A. G. Dialkyl ether formation by nickel-catalyzed cross-coupling of acetals and aryl iodides. Angew. Chem. Int. Ed. 54, 9876–9880 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge financial support from NIGMS (R01 GM100985). The authors also thank M.S. Sigman (University of Utah) for helpful suggestions on this manuscript and B. Shields, T. Graham (Merck) and D. Ahneman for discussions.

Author information

Authors and Affiliations

  1. Department of Chemistry, Princeton University, Princeton, 08544, New Jersey, USA

    Kevin Wu & Abigail G. Doyle

Authors
  1. Kevin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abigail G. Doyle
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.W. and A.G.D. conceived the work. K.W. performed and analysed the experiments and calculations. K.W. and A.G.D. designed the experiments, analysed the data and co-wrote the paper.

Corresponding author

Correspondence to Abigail G. Doyle.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 9495 kb)

Supplementary information

Crystallographic data for compound S-1. (CIF 3477 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, K., Doyle, A. Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects. Nature Chem 9, 779–784 (2017). https://doi.org/10.1038/nchem.2741

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2741

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