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Iron-catalysed regioselective thienyl C–H/C–H coupling

Abstract

Regioselective thienyl–thienyl coupling is arguably one of the most important transformations for organic electronic materials. A prototype of ideal organic synthesis to couple two thienyl groups by cutting two C–H bonds requires formal removal of two hydrogen atoms with an oxidant, which often limits the synthetic efficiency and versatility for oxidation-sensitive substrates (for example, donor and hole-transporting materials). Here, we found that diethyl oxalate, used together with AlMe3, acts as a two-electron acceptor in an iron-catalysed C–H activation. We describe the regioselective thienyl C–H/C–H coupling with an iron(III) catalyst, a trisphosphine ligand, AlMe3 and diethyl oxalate under mild conditions. The efficient catalytic system accelerated by ligand optimization polymerizes thiophene-containing monomers into homo- and copolymers bearing a variety of electron-donative π motifs. The findings suggest the versatility of iron catalysis for the synthesis of functional polymers, for which the potential of this ubiquitous metal has so far not been fully appreciated.

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Fig. 1: Iron-catalysed regioselective thienyl C–H/C–H coupling enabled by the TP/AlMe3/DEO system.
Fig. 2: Investigation of reaction parameters.
Fig. 3: Investigation of the ligand effect on polycondensation.
Fig. 4: Scope of iron-catalysed regioselective thienyl C–H/C–H homocoupling.
Fig. 5: Scope of iron-catalysed regioselective thienyl C–H/C–H polycondensation.

Data availability

All of the data supporting the findings of this study, including experimental procedures and compound characterization, are available within the paper and its Supplementary Information, or from the authors upon reasonable request.

References

  1. Handbook of Thiophene-Based Materials: Applications in Organic Electronics and Photonics Vols 1 and 2 (eds Perepichka, I. F. & Perepichka, D. F.) (Wiley, 2009).

  2. Stuart, D. R. & Fagnou, K. The catalytic cross-coupling of unactivated arenes. Science 316, 1172–1175 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Lyons, T. W. & Sanford, M. S. Palladium-catalyzed ligand-directed C–H functionalization reactions. Chem. Rev. 110, 1147–1169 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yang, Y., Lan, J. & You, J. Oxidative C–H/C–H coupling reactions between two (hetero)arenes. Chem. Rev. 117, 8787–8863 (2017).

    Article  CAS  PubMed  Google Scholar 

  5. Yang, Y., Nishiura, M., Wang, H. & Hou, Z. Metal-catalyzed C–H activation for polymer synthesis and functionalization. Coord. Chem. Rev. 376, 506–532 (2018).

    Article  CAS  Google Scholar 

  6. Gao, G.-L., Xia, W., Jain, P. & Yu, J.-Q. Pd(II)-catalyzed C3-selective arylation of pyridine with (hetero)arenes. Org. Lett. 18, 744–747 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Grzybowski, M., Skonieczny, K., Butenschön, H. & Gryko, D. T. Comparison of oxidative aromatic coupling and the Scholl reaction. Angew. Chem. Int. Ed. 52, 9900–9930 (2013).

    Article  CAS  Google Scholar 

  8. Takahashi, M. et al. Palladium-catalyzed C–H homocoupling of bromothiophene derivatives and synthetic application to well-defined oligothiophenes. J. Am. Chem. Soc. 128, 10930–10933 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Wang, L. & Carrow, B. P. Oligothiophene synthesis by a general C–H activation mechanism: electrophilic concerted metalation–deprotonation (eCMD). ACS Catal. 9, 6821–6836 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arndtsen, B. A., Bergman, R. G., Mobley, T. A. & Peterson, T. H. Selective intermolecular carbon–hydrogen bond activation by synthetic metal complexes in homogeneous solution. Acc. Chem. Res. 28, 154–162 (1995).

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Shang, R., Ilies, L. & Nakamura, E. Iron-catalyzed C–H bond activation. Chem. Rev. 117, 9086–9139 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. Doba, T., Matsubara, T., Ilies, L., Shang, R. & Nakamura, E. Homocoupling-free iron-catalysed twofold C–H activation/cross-couplings of aromatics via transient connection of reactants. Nat. Catal. 2, 400–406 (2019).

    Article  CAS  Google Scholar 

  14. Yu, R. P., Hesk, D., Rivera, N., Pelczer, I. & Chirik, P. J. Iron-catalysed tritiation of pharmaceuticals. Nature 529, 195–199 (2016).

    Article  PubMed  CAS  Google Scholar 

  15. Gandeepan, P. et al. 3d Transition metals for C–H activation. Chem. Rev. 119, 2192–2452 (2019).

    Article  CAS  PubMed  Google Scholar 

  16. Guo, X., Baumgarten, M. & Müllen, K. Designing π-conjugated polymers for organic electronics. Prog. Polym. Sci. 38, 1832–1908 (2013).

    Article  CAS  Google Scholar 

  17. Bujak, P. et al. Polymers for electronics and spintronics. Chem. Soc. Rev. 42, 8895–8999 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Shirota, Y. & Kageyama, H. Charge carrier transporting molecular materials and their applications in devices. Chem. Rev. 107, 953–1010 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Cheng, Y.-J., Yang, S.-H. & Hsu, C.-S. Synthesis of conjugated polymers for organic solar cell applications. Chem. Rev. 109, 5868–5923 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Wang, C., Dong, H., Hu, W., Liu, Y. & Zhu, D. Semiconducting π-conjugated systems in field-effect transistors: a material odyssey of organic electronics. Chem. Rev. 112, 2208–2267 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Pouliot, J.-R., Grenier, F., Blaskovits, J. T., Beaupré, S. & Leclerc, M. Direct (hetero)arylation polymerization: simplicity for conjugated polymer synthesis. Chem. Rev. 116, 14225–14274 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. Mercier, L. G. & Leclerc, M. Direct (hetero)arylation: a new tool for polymer chemists. Acc. Chem. Res. 46, 1597–1605 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. Rudenko, A. E. & Thompson, B. C. Optimization of direct arylation polymerization (DArP) through the identification and control of defects in polymer structure. J. Polym. Sci. A Polym. Chem. 53, 135–147 (2015).

    Article  CAS  Google Scholar 

  24. Bura, T., Blaskovits, J. T. & Leclerc, M. Direct (hetero)arylation polymerization: trends and perspectives. J. Am. Chem. Soc. 138, 10056–10071 (2016).

    Article  CAS  PubMed  Google Scholar 

  25. Blaskovits, J. T. & Leclerc, M. C–H activation as a shortcut to conjugated polymer synthesis. Macromol. Rapid Commun. 40, 1800512 (2019).

    Article  CAS  Google Scholar 

  26. Dudnik, A. S. et al. Tin-free direct C–H arylation polymerization for high photovoltaic efficiency conjugated copolymers. J. Am. Chem. Soc. 138, 15699–15709 (2016).

    Article  CAS  PubMed  Google Scholar 

  27. Yoon, K.-Y. & Dong, G. Modular in situ functionalization strategy: multicomponent polymerization by palladium/norbornene cooperative catalysis. Angew. Chem. Int. Ed. 57, 8592–8596 (2018).

    Article  CAS  Google Scholar 

  28. Shang, R., Ilies, L. & Nakamura, E. Iron-catalyzed ortho C–H methylation of aromatics bearing a simple carbonyl group with methylaluminum and tridentate phosphine ligand. J. Am. Chem. Soc. 138, 10132–10135 (2016).

    Article  CAS  PubMed  Google Scholar 

  29. Shang, R., Ilies, L. & Nakamura, E. Iron-catalyzed directed C(sp2)–H and C(sp3)–H functionalization with trimethylaluminum. J. Am. Chem. Soc. 137, 7660–7663 (2015).

    Article  CAS  PubMed  Google Scholar 

  30. Salazar, C. A. et al. Tailored quinones support high-turnover Pd catalysts for oxidative C–H arylation with O2. Science 370, 1454–1460 (2020).

    CAS  PubMed  Google Scholar 

  31. Boddien, A. et al. Efficient dehydrogenation of formic acid using an iron catalyst. Science 333, 1733–1736 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Li, P., de Bruin, B., Reek, J. N. H. & Dzik, W. I. Photo- and thermal isomerization of (TP)Fe(CO)Cl2 [TP = bis(2-diphenylphosphinophenyl)phenylphosphine]. Organometallics 34, 5009–5014 (2015).

    Article  CAS  Google Scholar 

  33. Masui, K., Ikegami, H. & Mori, A. Palladium-catalyzed C–H homocoupling of thiophenes: facile construction of bithiophene structure. J. Am. Chem. Soc. 126, 5074–5075 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Tereniak, S. J., Bruns, D. L. & Stahl, S. S. Pd-catalyzed aerobic oxidative coupling of thiophenes: synergistic benefits of phenanthroline dione and a Cu cocatalyst. J. Am. Chem. Soc. 142, 20318–20323 (2020).

    Article  CAS  Google Scholar 

  35. Cho, H. Y. & Scott, L. T. Oxidative cyclotrimerization of unsaturated compounds with DDQ and triflic acid: an efficient synthetic route to triply-fused benzene rings. Tetrahedron Lett. 56, 3458–3462 (2015).

    Article  CAS  Google Scholar 

  36. Wakim, S., Blouin, N., Gingras, E., Tao, Y. & Leclerc, M. Poly(2,7-carbazole) derivatives as semiconductors for organic thin-film transistors. Macromol. Rapid Commun. 28, 1798–1803 (2007).

    Article  CAS  Google Scholar 

  37. Ikariya, T. & Yamamoto, A. Preparation and properties of methyliron complexes with tertiary phosphine ligands and their decomposition pathways through the formation of carbenoid intermediates. J. Organomet. Chem. 118, 65–77 (1976).

    Article  CAS  Google Scholar 

  38. Carothers, W. H. Polymerization. Chem. Rev. 8, 353–426 (1931).

    Article  CAS  Google Scholar 

  39. Flory, P. J. Fundamental principles of condensation polymerization. Chem. Rev. 39, 137–197 (1946).

    Article  CAS  PubMed  Google Scholar 

  40. Watson, M. D., Fechtenkötter, A. & Müllen, K. Big is beautiful—“aromaticity” revisited from the viewpoint of macromolecular and supramolecular benzene chemistry. Chem. Rev. 101, 1267–1300 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Wu, Y. et al. Influence of nonfused cores on the photovoltaic performance of linear triphenylamine-based hole-transporting materials for perovskite solar cells. ACS Appl. Mater. Interfaces 10, 17883–17895 (2018).

    Article  CAS  PubMed  Google Scholar 

  42. Donat-Bouillud, A. et al. Light-emitting diodes from fluorene-based π-conjugated polymers. Chem. Mater. 12, 1931–1936 (2000).

    Article  CAS  Google Scholar 

  43. Calió, L., Kazim, S., Grätzel, M. & Ahmad, S. Hole-transport materials for perovskite solar cells. Angew. Chem. Int. Ed. 55, 14522–14545 (2016).

    Article  CAS  Google Scholar 

  44. Roncali, J. Conjugated poly(thiophenes): synthesis, functionalization, and applications. Chem. Rev. 92, 711–738 (1992).

    Article  CAS  Google Scholar 

  45. Ando, T., Kamigaito, M. & Sawamoto, M. Iron(II) chloride complex for living radical polymerization of methyl methacrylate. Macromolecules 30, 4507–4510 (1997).

    Article  CAS  Google Scholar 

  46. Matyjaszewski, K., Wei, M., Xia, J. & McDermott, N. E. Controlled/“living” radical polymerization of styrene and methyl methacrylate catalyzed by iron complexes. Macromolecules 30, 8161–8164 (1997).

    Article  CAS  Google Scholar 

  47. Bullock, R. M. et al. Using nature’s blueprint to expand catalysis with Earth-abundant metals. Science 369, eabc3183 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nakamura, E. & Sato, K. Managing the scarcity of chemical elements. Nat. Mater. 10, 158–161 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Still, W. C., Kahn, M. & Mitra, A. Rapid chromatographic technique for preparative separations with moderate resolution. J. Org. Chem. 43, 2923–2925 (1978).

    Article  CAS  Google Scholar 

  50. Pangborn, A. B., Giardello, M. A., Grubbs, R. H., Rosen, R. K. & Timmers, F. J. Safe and convenient procedure for solvent purification. Organometallics 15, 1518–1520 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Mitsubishi Chemical Corporation for partial financial support. We thank S. Kobayashi and T. Yasukawa for generous help with the ICP analysis of the contents of metal residues. This research is supported by MEXT KAKENHI grant number 19H05459 (to E.N.) and JSPS KAKENHI grant number 19K15555 (to R.S.). T.D. thanks JSPS for the predoctoral fellowship.

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E.N. and R.S. guided the research and wrote the manuscript. T.D. performed the experiments to develop the reaction and study the scope, application and mechanism. L.I. contributed to the optimization of dimerization. W.S. helped with polymer design, purification and characterization of properties. All authors contributed to designing the experiments, analysing the data and editing the manuscript.

Corresponding authors

Correspondence to Rui Shang or Eiichi Nakamura.

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Competing interests

E.N., R.S., T.D. and W.S. are inventors on Japanese patent application number 2020-130678, submitted by The University of Tokyo, which covers synthetic methods described in this manuscript. L.I. declares no competing interests.

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

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Supplementary Information

Supplementary Methods, Discussion, Tables 1–6 and Figs. 1–13.

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Doba, T., Ilies, L., Sato, W. et al. Iron-catalysed regioselective thienyl C–H/C–H coupling. Nat Catal 4, 631–638 (2021). https://doi.org/10.1038/s41929-021-00653-7

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