The highly surprising behaviour of diphosphine ligands in iron-catalysed Negishi cross-coupling

Abstract

Iron-catalysed cross-coupling is undergoing explosive development, but mechanistic understanding lags far behind synthetic methodology. Here, we find that the activity of iron–diphosphine pre-catalysts in the Negishi coupling of benzyl halides is strongly dependent on the diphosphine, but the ligand does not appear to be coordinated to the iron during turnover. This was determined using time-resolved in operando X-ray absorption fine structure spectroscopy employing a custom-made flow cell and confirmed by 31P NMR spectroscopy. While the diphosphine ligands tested are all able to coordinate to iron(ii), in the presence of excess zinc(ii)—as in the catalytic reaction—they coordinate predominantly to the zinc. Furthermore, combined synthetic and kinetic investigations implicate the formation of a putative mixed Fe–Zn(dpbz) species before the rate-limiting step of catalysis. These unexpected findings may not only impact the field of iron-catalysed Negishi cross-coupling, but potentially beyond to reactions catalysed by other transition metal/diphosphine complexes.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Generalized transition-metal-catalysed cross-coupling reactions.
Fig. 2: Activity of diphosphines in a representative iron-catalysed Negishi cross-coupling.
Fig. 3: Single-crystal X-ray structures of FeBr2–diphosphine adducts.
Fig. 4: Iron(i) versus iron(ii) in the Negishi coupling reaction.
Fig. 5: Time-resolved XAFS spectroscopy studies.
Fig. 6: Single-crystal X-ray structures of Zn(ii)–diphosphine adducts.
Fig. 7: Transmetallation studies.
Fig. 8: Schematic of a tentative suggestion for the role of chelating diphosphine in the catalytic reaction.

Data availability

Crystal structure data have been deposited at the Cambridge Crystallographic Data Centre (CCDC nos. 1836928–1836960 and 1868985) and crystallographic data are provided in the Supplementary Information. The spectroscopic, mass spectrometric, TEM and kinetic data that support the findings of this study are freely available in the University of Bristol data repository, data.bris, with the identifier https://doi.org/10.5523/bris.1kp2f62x3klb02mfz2qymcmxmx.

References

  1. 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).

    CAS  Article  Google Scholar 

  2. 2.

    Nakamura, E. et al. Iron-catalyzed cross-coupling reactions. Org. React. 83, 1–210 (2014).

    CAS  Google Scholar 

  3. 3.

    Bedford, R. B. & Brenner, P. B. The development of iron catalysts for cross-coupling reactions. Top. Organomet. Chem. 50, 19–46 (2015).

    CAS  Article  Google Scholar 

  4. 4.

    Bauer, I. & Knölker, H.-J. Iron catalysis in organic synthesis. Chem. Rev. 115, 3170–3387 (2015).

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Bedford, R. B. How low does iron go? Chasing the active species in Fe-catalyzed cross-coupling reactions. Acc. Chem. Res. 48, 1485–1493 (2015).

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Cassani, C., Bergonzini, G. & Wallentin, C.-J. Active species and mechanistic pathways in iron-catalyzed C−C bond-forming cross-coupling reactions. ACS Catal. 6, 1640–1648 (2016).

    CAS  Article  Google Scholar 

  7. 7.

    Mako, T. L. & Byers, J. A. Recent advances in iron-catalysed cross coupling reactions and their mechanistic underpinning. Inorg. Chem. Front. 3, 766–790 (2016).

    CAS  Article  Google Scholar 

  8. 8.

    Parchomyk, T. & Koszinowski, K. Iron-catalyzed cross-coupling: mechanistic insight for rational applications in synthesis. Synthesis 49, 3269–3280 (2017).

    CAS  Article  Google Scholar 

  9. 9.

    Bedford, R. B. et al. Iron-phosphine, -phosphite, -arsine and -carbene catalysts for the coupling of primary and secondary alkyl halides with aryl Grignard reagents. J. Org. Chem. 71, 1104–1110 (2006).

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Dongol, K. G., Koh, H., Sau, M. & Chai, C. L. L. Iron-catalysed sp 3sp 3 cross-coupling reactions of unactivated alkyl halides with alkyl Grignard reagents. Adv. Synth. Catal. 349, 1015–1018 (2007).

    CAS  Article  Google Scholar 

  11. 11.

    Bedford, R. B., Huwe, M. & Wilkinson, M. C. Iron-catalysed Negishi coupling of benzyl halides and phosphates. Chem. Commun. 600–602 (2009).

  12. 12.

    Hatakeyama, T. et al. Iron-catalysed fluoroaromatic coupling reactions under catalytic modulation with 1,2-bis(diphenylphosphino)benzene. Chem. Commun. 1216–1218 (2009)..

  13. 13.

    Bedford, R. B., Hall, M. A., Hodges, G. R., Huwe, M. & Wilkinson, M. C. Simple mixed Fe–Zn catalysts for the Suzuki couplings of tetraarylborates with benzyl halides and 2-halopyridines. Chem. Commun. 6430–6432 (2009).

  14. 14.

    Kawamura, S., Ishizuka, K., Takaya, H. & Nakamura, M. The first iron-catalysed aluminium-variant Negishi coupling: critical effect of co-existing salts on the dynamic equilibrium of arylaluminium species and their reactivity. Chem. Commun. 46, 6054–6056 (2010).

    CAS  Article  Google Scholar 

  15. 15.

    Hatakeyama, T. et al. Iron-catalyzed Suzuki-Miyaura coupling of alkyl halides. J. Am. Chem. Soc. 132, 10674–10676 (2010).

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Hatakeyama, T. et al. Kumada-Tamao-Corriu coupling of alkyl halides catalyzed by an iron–bisphosphine complex. Chem. Lett. 40, 1030–1032 (2011).

    CAS  Article  Google Scholar 

  17. 17.

    Hatakeyama, T., Okada, Y., Yoshimoto, Y. & Nakamura, M. Tuning chemoselectivity in iron-catalyzed Sonogashira-type reactions using a bisphosphine ligand with peripheral steric bulk: selective alkynylation of nonactivated alkyl halides. Angew. Chem. Int. Ed. 50, 10973–10976 (2011).

    CAS  Article  Google Scholar 

  18. 18.

    Lin, X., Zheng, F. & Qing, F.-L. Iron-catalyzed cross-coupling reactions between arylzinc reagents and alkyl halides bearing β-fluorines. Organometallics 31, 1578–1582 (2012).

    CAS  Article  Google Scholar 

  19. 19.

    Kawamura, S., Kawabata, T., Ishizuka, K. & Nakamura, M. Iron-catalysed cross-coupling of halohydrins with aryl aluminium reagents: a protecting-group-free strategy attaining remarkable rate enhancement and diastereoinduction. Chem. Commun. 48, 9376–9378 (2012).

    CAS  Article  Google Scholar 

  20. 20.

    Hashimoto, T., Hatakeyama, T. & Nakamura, M. Stereospecific cross-coupling between alkenylboronates and alkyl halides catalyzed by iron–bisphosphine complexes. J. Org. Chem. 77, 1168–1173 (2012).

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Hatakeyama, T. et al. Iron-catalyzed alkyl–alkyl Suzuki-Miyaura coupling. Angew. Chem. Int. Ed. 51, 8834–8837 (2012).

    CAS  Article  Google Scholar 

  22. 22.

    Adams, C. J. et al. Iron(i) in Negishi cross-coupling reactions. J. Am. Chem. Soc. 134, 10333–10336 (2012).

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Kawamura, S. & Nakamura, M. Ligand-controlled iron-catalyzed cross coupling of benzylic chlorides with aryl Grignard reagents. Chem. Lett. 42, 183–185 (2013).

    CAS  Article  Google Scholar 

  24. 24.

    Bedford, R. B. et al. Simplifying iron–phosphine catalysts for cross-coupling reactions. Angew. Chem. Int. Ed. 52, 1285–1288 (2013).

    CAS  Article  Google Scholar 

  25. 25.

    Sun, C.-L., Krause, H. & Fürstner, A. A practical procedure for iron-catalyzed cross-coupling reactions of sterically hindered aryl-Grignard reagents with primary alkyl halides. Adv. Synth. Catal. 356, 1281–1291 (2014).

    CAS  Article  Google Scholar 

  26. 26.

    Bedford, R. B. et al. Iron phosphine catalyzed cross-coupling of tetraorganoborates and related group 13 nucleophiles with alkyl halides. Organometallics 33, 5767–5780 (2014).

    CAS  Article  Google Scholar 

  27. 27.

    Bedford, R. B. et al. Expedient iron-catalyzed coupling of alkyl, benzyl and allyl halides with arylboronic esters. Chem. Eur. J. 20, 7935–7938 (2014).

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Clifton, J., Habraken, E. R. M., Pringle, P. G. & Manners, I. Subtle effects of ligand backbone on the efficienct of iron-diphos catalysed Negishi cross-coupling reactions. Catal. Sci. Technol. 5, 4350–4353 (2015).

    CAS  Article  Google Scholar 

  29. 29.

    Daifuku, S. L., Al-Afyouni, M. H., Snyder, B. E. R., Kneebone, J. L. & Neidig, M. L. A combined Mössbauer, magnetic circular dichroism, and density functional theory approach for iron cross-coupling catalysis: electronic structure, in situ formation and reactivity of iron-mesityl-bisphosphines. J. Am. Chem. Soc. 136, 9132–9143 (2014).

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Daifuku, S. L., Kneebone, J. L., Snyder, B. E. R. & Neidig, M. L. Iron(ii) active species in iron–bisphosphine catalyzed Kumada and Suzuki−Miyaura cross-couplings of phenyl nucleophiles and secondary alkyl halides. J. Am. Chem. Soc. 137, 11432–11444 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Falivene, L. et al. SambVca 2. A web tool for analyzing catalytic pockets with topographic steric maps. Organometallics 35, 2286–2293 (2016).

    CAS  Article  Google Scholar 

  32. 32.

    Lovitt, C. F., Frenking, G. & Girolami, G. S. Donor–acceptor properties of bidentate phosphines. DFT study of nickel carbonyls and molecular dihydrogen complexes. Organometallics 31, 4122–4132 (2012).

    Article  Google Scholar 

  33. 33.

    Jover, J. & Fey, N. Screening substituent and backbone effects on the properties of bidentate P,P-donor ligands (LKB-PPscreen). Dalton Trans. 42, 172–181 (2013).

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Takaya, H. et al. Investigation of organoiron catalysis in Kumada–­Tamao­–Corriu-type cross-coupling reaction assisted by solution-phase X-ray absorption spectroscopy. Bull. Chem. Soc. Jpn 88, 410–418 (2015).

    CAS  Article  Google Scholar 

  35. 35.

    Langer, R. et al. Substitional lability of diphosphine ligands in tetrahedral iron(ii) chloro complexes. Eur. J. Inorg. Chem. 2015, 141–148 (2015).

    CAS  Article  Google Scholar 

  36. 36.

    Barclay, J. E., Hills, A., Hughes, D. L. & Leigh, G. J. Crystal and molecular structures of four bis(diphosphine) complexes of iron(ii): bis[1.2-bis(diethylphosphino)ethane]di-iodoiron(ii), dichlorobis[o-phenylenebis(diphenylphosphine)]iron(ii), bis(acetonitrile)bis[o-phenylenebis(diphenylphosphine)]iron(ii)di-iodide, and lodobis-[o-phenylenebis(diphenylphosphine)]iron(ii) iodide. J. Chem. Soc. Dalton Trans. 2871–2877 (1988).

  37. 37.

    Evans, D. J., Henderson, R. A., Hills, A., Hughes, D. L. & Oglieve, K. E. Involvement of iron alkyl complexes and alkyl radicals in the Kharasch reactions: probing the catalysis using iron phosphine complexes. J. Chem. Soc. Dalton Trans. 1259–1265 (1992).

  38. 38.

    Wu, C.-C., Jung, J., Gantzel, P. K., Gütlich, P. & Hendrickson, D. N. LIESST effect studies of iron(ii) spin-crossover complexes with phosphine ligands: relaxation kinetics and effects of solvent molecules. Inorg. Chem. 36, 5339–5347 (1997).

    CAS  Article  Google Scholar 

  39. 39.

    Schoch, R., Desens, W., Werner, T. & Bauer, M. X-ray spectroscopic verification of the active species in iron-catalyzed cross-coupling reactions. Chem. Eur. J. 19, 15816–15821 (2013).

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Welther, A., Bauer, M., Mayer, M. & Jacobi, Von Wangelin iron(0) particles: catalytic hydrogenations and spectroscopic studies. ChemCatChem 4, 1088–1093 (2012).

    CAS  Article  Google Scholar 

  41. 41.

    Bedford, R. B. et al. Iron nanoparticles in the coupling of alkyl halides with aryl Grignard reagents. Chem. Commun. 1398–1400 (2006).

  42. 42.

    Bedford, R. B. et al. TMEDA in iron-catalyzed Kumada coupling: amine adduct versus homoleptic ‘ate’ complex formation. Angew. Chem. Int. Ed. 53, 1804–1808 (2014).

    CAS  Article  Google Scholar 

  43. 43.

    Klose, A. et al. Magnetic properties diagnostic for the existence of iron(ii)–iron(ii) bonds in dinuclear complexes which derive from stepwise insertion reactions on unsupported iron–aryl bonds. J. Am. Chem. Soc. 116, 9123–9135 (1994).

    CAS  Article  Google Scholar 

  44. 44.

    Jefferis, J. M. & Girolami, G. S. Crystal structure of ‘[Li(Et2O)]4[FePh4]’: corrigendum and reformulation. A remarkable example of a false solution in a wrong space group. Organometallics 17, 3630–3632 (1998).

    CAS  Article  Google Scholar 

  45. 45.

    Huang, F. et al. C–H bond activation/borylation of furans and thiophenes catalyzed by a half‐sandwich iron N‐heterocyclic carbene complex. Chem. Asian J. 5, 1657–1666 (2010).

    Article  Google Scholar 

  46. 46.

    Kalman, S. E. et al. Facile and regioselective C−H bond activation of aromatic substrates by an Fe(ii) complex involving a spin-forbidden pathway. Organometallics 32, 1797–1806 (2013).

    CAS  Article  Google Scholar 

  47. 47.

    Goedken, V. L., Peng, S.-M. & Park, Y. A new route to the formation of organocobalt(iii) and organoiron(iii) complexes. Alkylation via oxidative deamination of organic hydrazines. J. Am. Chem. Soc. 96, 284–285 (1974).

    CAS  Article  Google Scholar 

  48. 48.

    Sciarone, T. J. J., Meetsma, A., Hesssen, B. & Teuben, J. H. Benzyl anion abstraction from a (β-diiminato)Fe(ii) benzyl complex. Chem. Commun. 1580–1581 (2002).

  49. 49.

    Mund, G. et al. Unusual iron(iii) ate complexes stabilized by Li–π interactions. Chem. Eur. J. 9, 4757–4763 (2003).

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Rose, R. P., Jones, C., Schulten, C., Aldridge, S. & Stasch, A. Synthesis and characterization of amidinate–iron(i) complexes: analogies with β‐diketiminate chemistry. Chem. Eur. J. 14, 8477–8480 (2008).

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Taherimehr, M., Al-Amsyar, S. M., Whiteoak, C. J., Kleij, A. W. & Pescarmona, P. P. High activity and switchable selectivity in the synthesis of cyclic and polymeric cyclohexene carbonates with iron amino triphenolate catalysts. Green Chem. 15, 3083–3090 (2013).

    CAS  Article  Google Scholar 

  52. 52.

    Lichtenberg, C. et al. Mono- and dinuclear neutral and cationic iron(ii) compounds supported by an amidinato-diolefin ligand: characterization and catalytic application. Organometallics 34, 3079–3089 (2015).

    CAS  Article  Google Scholar 

  53. 53.

    Trovitch, R. J., Lobkovsky, E. & Chirik, P. J. Bis(imino)pyridine iron alkyls containing β-hydrogens: synthesis, evaluation of kinetic stability and decomposition pathways involving chelate participation. J. Am. Chem. Soc. 130, 11631–11640 (2008).

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Ouyang, Z. et al. Linear and T‐shaped iron(i) complexes supported by N‐heterocyclic carbene ligands: synthesis and structure characterization. Inorg. Chem. 54, 8808–8816 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Ohki, Y., Hoshino, R. & Tatsumi, K. N-Heterocyclic carbene complexes of three- and four-coordinate Fe(i). Organometallics 35, 1368–1375 (2016).

    CAS  Article  Google Scholar 

  56. 56.

    Tromp, M., Moulin, J., Reid, G. & Evans, J. Cr K-edge XANES spectroscopy: ligand and oxidation state dependence—what is oxidation state? AIP Conference Proceedings 882, 699–701 (2007).

    CAS  Article  Google Scholar 

  57. 57.

    Liu, X., Liu, Y., Hao, Y., Yang, X.-J. & Wu, B. Square helix versus zigzag chain of group 12 metal coordination polymers with 1,2-bis(diphenylphosphino)ethane (dppe). Inorg. Chem. Comm. 13, 511–513 (2010).

    CAS  Article  Google Scholar 

  58. 58.

    Dunsford, J. J., Clark, E. R. & Ingleson, M. J. Direct C(sp 2)–C(sp 3) cross-coupling of diaryl zinc reagents with benzylic, primary, secondary and tertiary alkyl halides. Angew. Chem. Int. Ed. 54, 5688–5692 (2015).

    CAS  Article  Google Scholar 

  59. 59.

    Abbenhuis, H. C. L. et al. A bimetallic tantalum–zinc complex with an ancillary aryldiamine ligand as precursor for a reactive alkylidyne species: alkylidyne-mediated C–H activation and a palladium-mediated alkylidyne functionalization. Organometallics 12, 2227–2235 (1993).

    CAS  Article  Google Scholar 

  60. 60.

    Liberman-Martin, A. L., Levine, D. S., Ziegler, M. S., Bergman, R. G. & Tilley, T. D. Lewis acid–base interactions between platinum(ii) diaryl complexes and bis(perfluorophenyl)zinc: strongly accelerated reductive elimination induced by a Z-type ligand. Chem. Commun. 52, 7039–7042 (2016).

    CAS  Article  Google Scholar 

  61. 61.

    Garden, J. A., White, A. J. P. & Williams, C. K. Heterodinuclear titanium/zinc catalysis: synthesis, characterization and activity for CO2/epoxide copolymerization and cyclic ester polymerization. Dalton Trans. 46, 2532–2541 (2017).

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

The authors thank the following for supporting the project: the UK Catalysis Hub for resources and support provided via our membership of the UK Catalysis Hub Consortium and funded by EPSRC (grants nos. EP/K014706/2, EP/K014668/1, EP/K014854/1, EP/K014714/1 and EP/M013219/1); the EPSRC for funding (grant no. EP/K012258/1), the provision of a studentship through the EPSRC Centre for Doctoral Training in Catalysis (to S.L.J.L.) and for a part-studentship (to H.M.O’B.); AstraZeneca for CASE top-up funding (to H.M.O’B.) and CONACYT (studentship for O.H.F.). The authors thank Diamond Light Source and the UK Catalysis Hub for award of beamtime through the BAG allocation to B18 (SP15151). The authors thank N. Fey for provision of and discussions concerning Ligand Knowledge Base data and P. Lawrence for help with setting up NMR experiments.

Author information

Affiliations

Authors

Contributions

A.M.M., S.L.J.L., D.G., E.K.G., H.M.O’B., H.A.S., S.A.D., J.C., D.E., O.H.-F. and R.B.B. performed and analysed experiments. A.M.M. and P.P.W. designed the flow-XAFS cell. P.P.W., A.M.M., D.G., E.K.G. and J.C. designed XAFS experiments. A.M.M., S.L.J.L. and R.B.B. designed synthetic and mechanistic experiments. R.B.B. designed computational experiments. R.B.B., A.M.M., P.P.W. and S.L.J.L. prepared this manuscript.

Corresponding author

Correspondence to Robin B. Bedford.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Supplementary information

Supplementary Information

Supplementary Methods, Supplementary Figures 1–231, Supplementary Tables 1–25, Supplementary References

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Messinis, A.M., Luckham, S.L.J., Wells, P.P. et al. The highly surprising behaviour of diphosphine ligands in iron-catalysed Negishi cross-coupling. Nat Catal 2, 123–133 (2019). https://doi.org/10.1038/s41929-018-0197-z

Download citation

Further reading