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

Nature Chemistry volume 10, pages 218224 (2018) | Download Citation

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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.

  • Compound

    N-(tert-butyl)benzamide

  • Compound

    triethoxy(4-(trifluoromethyl)phenyl)silane

  • Compound

    tetrabutylammonium triethoxyfluoro(4-(trifluoromethyl)phenyl)silicate(IV)

  • Compound

    N-(tert-butyl)-2(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-(tert-butyl)-4-methyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-adamantyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-adamantyl-4-methyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-cyclohexyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-propyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-adamantyl-4-methoxy-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-adamantyl-4-trifluoromethyl-2-(4-(trifluoromethyl)phenyl)benzamide

  • Compound

    N-adamantyl-2-(4-bromophenyl)benzamide

  • Compound

    N-adamantyl-2-(4-chlorophenyl)benzamide

  • Compound

    N-adamantyl-2-(3,4-difluorophenyl)benzamide

  • Compound

    N-adamantyl-2-(3-chloro-4-fluorophenyl)benzamide

  • Compound

    (Z)-N-adamantyl-2-methyl-3-(4-(trifluoromethyl)phenyl)but-2-enamide

  • Compound

    (Z)-N-adamantyl-2-methyl-3-(4-chlorophenyl)but-2-enamide

  • Compound

    N-(tert-Butyl)-2-(4-(trifluoromethyl)phenyl)cyclohex-1-ene-1-carboxamide

  • Compound

    N-(5-methyl-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)pivalamide

  • Compound

    N-pivaloyl-5-methyl-7-(4-(trifluoromethyl)phenyl)indoline

  • Compound

    5-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one

  • Compound

    10-(4-(trifluoromethyl)phenyl)benzo[h]quinoline

  • Compound

    benzamide-containing iridacycle

  • Compound

    iridium(III)-aryl intermediate

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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.

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Acknowledgements

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

Author information

Affiliations

  1. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

    • Kwangmin Shin
    • , Yoonsu Park
    • , Mu-Hyun Baik
    •  & Sukbok Chang
  2. Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Republic of Korea

    • Kwangmin Shin
    • , Yoonsu Park
    • , Mu-Hyun Baik
    •  & Sukbok Chang

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mu-Hyun Baik or Sukbok Chang.

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DOI

https://doi.org/10.1038/nchem.2900