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Iridium-catalysed arylation of C–H bonds enabled by oxidatively induced reductive elimination

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Abstract

Direct arylation of C–H bonds is in principle a powerful way of preparing value-added molecules that contain carbon–aryl fragments. Unfortunately, currently available synthetic methods are not sufficiently effective to be practical alternatives to conventional cross-coupling reactions. We propose that the main problem lies in the late portion of the catalytic cycle where reductive elimination gives the desired carbon–aryl bond. Accordingly, we have developed a strategy where the Ir(III) centre of the key intermediate is first oxidized to Ir(IV). Density functional theory calculations indicate that the barrier to reductive elimination is reduced by nearly 19 kcal mol–1 for this oxidized complex compared with that of its Ir(III) counterpart. Various experiments confirm this prediction, affording a new methodology capable of directly arylating C–H bonds at room temperature with a broad substrate scope and in good yields. This work highlights how the oxidation states of intermediates can be targeted deliberately to catalyse an otherwise impossible reaction.

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Figure 1: Schematic representation of C–H arylation reactions with aryl nucleophiles catalysed by transition-metal complexes.
Figure 2: Mechanistic studies on the transmetallation and oxidatively induced carbon–aryl bond-forming step of the present arylation.
Figure 3: Calculated energy profiles for the reductive elimination from Ir(III)–aryl, Ir(IV)–aryl and Ir(V)–aryl intermediates.
Figure 4: Detailed mechanistic studies on the oxidation and reductive elimination step of the present iridium-catalysed C−H arylation.
Figure 5: Proposed catalytic cycle of the present Ir(III)-catalysed C–H arylation.

Change history

  • 13 February 2018

    In the version of this Article originally published, the oxidation states of the iridium centres in figures 2, 4 and 5 were formatted incorrectly. These have been corrected after print.

References

  1. 1

    Dyker, G. Handbook of C−H Transformations Applications in Organic Synthesis (Wiley-VCH, 2005).

    Google Scholar 

  2. 2

    Ackermann, L., Vicente, R. & Kapdi, A. R. Transition-metal-catalyzed direct arylation of (hetero)arenes by C–H bond cleavage. Angew. Chem. Int. Ed. 48, 9792–9826 (2009).

    CAS  Google Scholar 

  3. 3

    Liu, C., Zhang, H., Shi, W. & Lei, A. Bond formations between two nucleophiles: transition metal catalyzed oxidative cross-coupling reactions. Chem. Rev. 111, 1780–1824 (2011).

    CAS  PubMed  Google Scholar 

  4. 4

    Giri, R., Thapa, S. & Kafle, A. Palladium-catalysed, directed C–H coupling with organometallics. Adv. Synth. Catal. 356, 1395–1411 (2014).

    CAS  Google Scholar 

  5. 5

    Lapointe, D. & Fagnou, K. Overview of the mechanistic work on the concerted metallation–deprotonation pathway. Chem. Lett. 39, 1118–1126 (2010).

    Google Scholar 

  6. 6

    Chu, J.-H., Lin, P.-S. & Wu, M.-J. Palladium(II)-catalyzed ortho arylation of 2-phenoxypyridines with potassium aryltrifluoroborates via C–H functionalization. Organometallics 29, 4058–4065 (2010).

    CAS  Google Scholar 

  7. 7

    Li, W., Yin, Z., Jiang, X. & Sun, P. Palladium-catalyzed direct ortho C–H arylation of 2-arylpyridine derivatives with aryltrimethoxysilane. J. Org. Chem. 76, 8543–8548 (2011).

    CAS  PubMed  Google Scholar 

  8. 8

    Romero-Revilla, J. A., García-Rubia, A., Goméz Arrayás, R., Fernández-Ibáñez, M. Á. & Carretero, J. C. Palladium-catalyzed coupling of arene C–H bonds with methyl- and arylboron reagents assisted by the removable 2-pyridylsulfinyl group. J. Org. Chem. 76, 9525–9530 (2011).

    CAS  PubMed  Google Scholar 

  9. 9

    Spangler, J. E., Kobayashi, Y., Verma, P., Wang, D.-H. & Yu, J.-Q. α-Arylation of saturated azacycles and N-methylamines via palladium(II)-catalyzed C(sp3)–H coupling. J. Am. Chem. Soc. 137, 11876–11879 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Komiya, S., Albright, T. A., Hoffmann, R. & Kochi, J. K. The stability of organogold compounds. Hydrolytic, thermal, and oxidative cleavages of dimethylaurate(I) and tetramethylaurate(III). J. Am. Chem. Soc. 99, 8440–8447 (1977).

    CAS  Google Scholar 

  11. 11

    Lau, W., Huffman, J. C. & Kochi, J. K. Electrochemical oxidation–reduction of organometallic complexes. Effect of the oxidation state on the pathways for reductive elimination of dialkyliron complexes. Organometallics 1, 155–169 (1982).

    CAS  Google Scholar 

  12. 12

    Seligson, A. L. & Trogler, W. C. One-electron oxidative cleavage of palladium(II) alkyl and phenoxo bonds. J. Am. Chem. Soc. 114, 7085–7089 (1992).

    CAS  Google Scholar 

  13. 13

    Pedersen, A. & Tilset, M. Oxidatively induced reductive eliminations. Kinetics and mechanism of the elimination of ethane from the 17-electron cation radical of rhodium complex Cp*Rh(PPh3)(CH3)2 . Organometallics 12, 56–64 (1993).

    CAS  Google Scholar 

  14. 14

    Koo, K. & Hillhouse, G. L. Carbon–nitrogen bond formation by reductive elimination from nickel(II) amido alkyl complexes. Organometallics 14, 4421–4423 (1995).

    CAS  Google Scholar 

  15. 15

    Lanci, M. P., Remy, M. S., Kaminsky, W., Mayer, J. M. & Sanford, M. S. Oxidatively induced reductive elimination from (tBu2bpy)Pd(Me)2: palladium(IV) intermediates in a one-electron oxidation reaction. J. Am. Chem. Soc. 131, 15618–15620 (2009).

    CAS  PubMed  Google Scholar 

  16. 16

    Bour, J. R. et al. Carbon–carbon bond-forming reductive elimination from isolated nickel(III) complexes. J. Am. Chem. Soc. 138, 16105–16111 (2016).

    CAS  PubMed  Google Scholar 

  17. 17

    Watson, M. B., Rath, N. P. & Mirica, L. M. Oxidative C–C bond formation reactivity of organometallic Ni(II), Ni(III), and Ni(IV) complexes. J. Am. Chem. Soc. 139, 35–38 (2017).

    CAS  PubMed  Google Scholar 

  18. 18

    Neufeldt, S. R., Seigerman, C. K. & Sanford, M. S. Mild palladium-catalyzed C–H alkylation using potassium alkyltrifluoroborates in combination with MnF3 . Org. Lett. 15, 2302–2305 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Seigerman, C. K., Micyus, T. M., Neufeldt, S. R. & Sanford, M. S. Palladium-catalyzed C–H arylation using aryltrifluoroborates in conjunction with a MnIII oxidant under mild conditions. Tetrahedron 69, 5580–5587 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Tasker, S. Z. & Jamison, T. F. Highly regioselective indoline synthesis under nickel/photoredox dual catalysis. J. Am. Chem. Soc. 137, 9531–9534 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Terrett, J. A., Cuthbertson, J. D., Shurtleff, V. W. & MacMillan, D. W. Switching on elusive organometallic mechanisms with photoredox catalysis. Nature 524, 330–334 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Corcoran, E. B. et al. Aryl amination using ligand-free Ni(II) salts and photoredox catalysis. Science 353, 279–283 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Shin, K., Park, S.-W. & Chang, S. Cp*Ir(III)-catalyzed mild and broad C–H arylation of arenes and alkenes with aryldiazonium salts leading to the external oxidant-free approach. J. Am. Chem. Soc. 137, 8584–8592 (2015).

    CAS  PubMed  Google Scholar 

  24. 24

    Li, L., Brennessel, W. W. & Jones, W. D. C−H activation of phenyl imines and 2-phenylpyridines with [Cp*MCl2]2 (M = Ir, Rh): regioselectivity, kinetics, and mechanism. Organometallics 28, 3492–3500 (2009).

    CAS  Google Scholar 

  25. 25

    Yang, S., Li, B., Wan, X. & Shi, Z. Ortho arylation of acetanilides via Pd(II)-catalyzed C–H functionalization. J. Am. Chem. Soc. 129, 6066–6067 (2007).

    CAS  PubMed  Google Scholar 

  26. 26

    Zhou, H., Xu, Y.-H., Chung, W.-J. & Loh, T.-P. Palladium-catalyzed direct arylation of cyclic enamides with aryl silanes by sp2 C–H activation. Angew. Chem. Int. Ed. 48, 5355–5357 (2009).

    CAS  Google Scholar 

  27. 27

    Senthilkumar, N., Parthasarathy, K., Gandeepan, P. & Cheng, C.-H. Synthesis of phenanthridinones from N-methoxybenzamides and aryltriethoxysilanes through Rh(III)-catalyzed C–H and N–H bond activation. Chem. Asian J. 8, 2175–2181 (2013).

    CAS  PubMed  Google Scholar 

  28. 28

    Lu, M.-Z., Lu, P., Xu, Y.-H. & Loh, T.-P. Mild Rh(III)-catalyzed direct C–H bond arylation of (hetero)arenes with arylsilanes in aqueous media. Org. Lett. 16, 2614–2617 (2014).

    CAS  PubMed  Google Scholar 

  29. 29

    He, J., Takise, R., Fu, H. & Yu, J.-Q. Ligand-enabled cross-coupling of C(sp3)–H bonds with arylsilanes. J. Am. Chem. Soc. 137, 4618–4621 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Zhao, S., Liu, B., Zhan, B.-B., Zhang, W.-D. & Shi, B.-F. Nickel-catalyzed ortho-arylation of unactivated (hetero)aryl C–H bonds with arylsilanes using a removable auxiliary. Org. Lett. 18, 4586–4589 (2016).

    CAS  PubMed  Google Scholar 

  31. 31

    Nareddy, P., Jordan, F. & Szostak, M. Highly chemoselective ruthenium(II)-catalyzed direct arylation of cyclic and N,N-dialkyl benzamides with aryl silanes. Chem. Sci. 8, 3204–3210 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Shukla, K. H. & DeShong, P. Studies on the mechanism of allylic coupling reactions: a Hammett analysis of the coupling of aryl silicate derivatives. J. Org. Chem. 73, 6283–6291 (2008).

    CAS  PubMed  Google Scholar 

  33. 33

    Saijo, H., Ohashi, M. & Ogoshi, S. Fluoroalkylcopper(I) complexes generated by the carbocupration of tetrafluoroethylene: construction of a tetrafluoroethylene-bridging structure. J. Am. Chem. Soc. 136, 15158–15161 (2014).

    CAS  PubMed  Google Scholar 

  34. 34

    Nakao, Y., Imanaka, H., Sahoo, A. K., Yada, A. & Hiyama, T. Alkenyl- and aryl[2-(hydroxymethyl)phenyl]dimethylsilanes: an entry to tetraorganosilicon reagents for the silicon-based cross-coupling reaction. J. Am. Chem. Soc. 127, 6952–6953 (2005).

    CAS  PubMed  Google Scholar 

  35. 35

    Herron, J. R. & Ball, Z. T. Synthesis and reactivity of functionalized arylcopper compounds by transmetalation of organosilanes. J. Am. Chem. Soc. 130, 16486–16487 (2008).

    CAS  PubMed  Google Scholar 

  36. 36

    Oeschger, R. J. & Chen, P. Structure and gas-phase thermochemistry of a Pd/Cu complex: studies on a model for transmetalation transition states. J. Am. Chem. Soc. 139, 1069–1072 (2017).

    CAS  PubMed  Google Scholar 

  37. 37

    Nakao, Y. & Hiyama, T. Silicon-based cross-coupling reaction: an environmentally benign version. Chem. Soc. Rev. 40, 4893–4901 (2011).

    CAS  PubMed  Google Scholar 

  38. 38

    Amatore, C., Grimaud, L., Le Duc, G. & Jutand, A. Three roles for the fluoride ion in palladium-catalyzed Hiyama reactions: transmetalation of [ArPdFL2] by Ar′Si(OR)3 . Angew. Chem. Int. Ed. 53, 6982–6985 (2014).

    CAS  Google Scholar 

  39. 39

    Whitaker, D., Burés, J. & Larrosa, I. Ag(I)-catalyzed C–H activation: the role of the Ag(I) salt in Pd/Ag-mediated C–H arylation of electron-deficient arenes. J. Am. Chem. Soc. 138, 8384–8387 (2016).

    CAS  PubMed  Google Scholar 

  40. 40

    Lotz, M. D., Camasso, N. M., Canty, A. J. & Sanford, M. S. Role of silver salts in palladium-catalyzed arene and heteroarene C–H functionalization reactions. Organometallics 36, 165–171 (2017).

    CAS  Google Scholar 

  41. 41

    Shen, Q. & Hartwig, J. F. Lewis acid acceleration of C–N bond-forming reductive elimination from heteroarylpalladium complexes and catalytic amidation of heteroaryl bromides. J. Am. Chem. Soc. 129, 7734–7735 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    Brewster, T. P. et al. An iridium(IV) species, [Cp*Ir(NHC)Cl]+, related to a water-oxidation catalyst. Organometallics 30, 965–973 (2011).

    CAS  Google Scholar 

  43. 43

    Graeupner, J. et al. Electron-rich CpIr(biphenyl-2,2′-diyl) complexes with π-accepting carbon donor ligands. Organometallics 31, 7158–7164 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Kang, J. W. & Maitlis, P. M. (Pentamethylcyclopentadienyl)rhodium and -iridium complexes. V. Complexes with oxy-ligands and the exchange of methyl protons by deuterium under basic conditions. J. Organomet. Chem. 30, 127–133 (1971).

    CAS  Google Scholar 

  45. 45

    Huang, L., Hackenberger, D. & Gooßen, L. J. Iridium-catalyzed ortho-arylation of benzoic acids with arenediazonium salts. Angew. Chem. Int. Ed. 54, 12607–12611 (2015).

    CAS  Google Scholar 

  46. 46

    Gao, P. et al. Iridium(III)-catalyzed direct arylation of C–H bonds with diaryliodonium salts. J. Am. Chem. Soc. 137, 12231–12240 (2015).

    CAS  PubMed  Google Scholar 

  47. 47

    Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemistry: calling all engineers. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.201707584 (2017).

    PubMed  Google Scholar 

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Acknowledgements

This research was supported by the Institute for Basic Science (IBS-R010-D1) in Korea.

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K.S., Y.P., M.-H.B. and S.C. conceived and designed the project and wrote the manuscript. K.S. and Y.P. carried out the experiments. Y.P. performed DFT calculations. S.C. organized the research. All authors analysed the data, discussed the results and commented on the manuscript.

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Correspondence to Mu-Hyun Baik or Sukbok Chang.

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Shin, K., Park, Y., Baik, MH. et al. Iridium-catalysed arylation of C–H bonds enabled by oxidatively induced reductive elimination. Nature Chem 10, 218–224 (2018). https://doi.org/10.1038/nchem.2900

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