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An efficient organocatalytic method for constructing biaryls through aromatic C–H activation

Nature Chemistry volume 2, pages 10441049 (2010) | Download Citation

Abstract

The direct functionalization of C–H bonds has drawn the attention of chemists for almost a century. C–H activation has mainly been achieved through four metal-mediated pathways: oxidative addition, electrophilic substitution, σ-bond metathesis and metal-associated carbene/nitrene/oxo insertion. However, the identification of methods that do not require transition-metal catalysts is important because methods involving such catalysts are often expensive. Another advantage would be that the requirement to remove metallic impurities from products could be avoided, an important issue in the synthesis of pharmaceutical compounds. Here, we describe the identification of a cross-coupling between aryl iodides/bromides and the C–H bonds of arenes that is mediated solely by the presence of 1,10-phenanthroline as catalyst in the presence of KOt-Bu as a base. This apparently transition-metal-free process provides a new strategy with which to achieve direct C–H functionalization.

  • Compound C13H12O

    4-Methoxybiphenyl

  • Compound C16H18O

    4'-Methoxy-2,4,6-trimethylbiphenyl

  • Compound C13H10F2O

    2,5-Difluoro-4'-methoxybiphenyl

  • Compound C15H16O

    2,5-Dimethyl-4'-methoxybiphenyl

  • Compound C12H13NO

    1-Methyl-2-(4-anisyl)-pyrrole

  • Compound C13H12O

    3-Methoxybiphenyl

  • Compound C13H12O

    2-Methoxybiphenyl

  • Compound C12H10

    Biphenyl

  • Compound C13H12

    4-Methylbiphenyl

  • Compound C13H12

    3-Methylbiphenyl

  • Compound C13H12

    2-Methylbiphenyl

  • Compound C14H14

    3,5-Dimethylbiphenyl

  • Compound C15H16O

    4-Methoxy-3,5-dimethylbiphenyl

  • Compound C18H14

    p-Terphenyl

  • Compound C13H9F3O

    4-Trifluoromethoxybiphenyl

  • Compound C12H9F

    4-Fluorobiphenyl

  • Compound C12H9Cl

    4-Chlorobiphenyl

  • Compound C13H9F3

    3-Trifluoromethylbiphenyl

  • Compound C13H9N

    4-Cyanobiphenyl

  • Compound C19H14O

    4-Benzoylbiphenyl

  • Compound C16H12

    1-Phenylnaphthalene

  • Compound C10H8N2

    2-Phenylpyrazine

  • Compound C15H11N

    4-Phenylisoquinoline

  • Compound C16H13N

    2-Methyl-6-phenylquinoline

  • Compound C13H10O

    6H-Benzo[c]chromene

  • Compound C12H8N2

    1,10-Phenanthroline

  • Compound C24H16N2

    4,7-Diphenyl-1,10-phenanthroline

  • Compound C14H12N2

    2,9-Dimethyl-1,10-phenanthroline

  • Compound C12H7N3O2

    5-Nitro-1,10-phenanthroline

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Acknowledgements

The authors acknowledge support for this work from NSFC (grant nos 20672006, 20821062, GZ419) and the ‘973’ Project from the MOST of China (2009CB825300). The authors also thank J. Zhang at East China Normal University and N. Jiao at the Medical School of Peking University and their students for repeating our experiments. The polishing of the English and the constructive comments from K. Itami at Nagoya University and C. He from the University of Chicago are greatly appreciated.

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Affiliations

  1. Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

    • Chang-Liang Sun
    • , Hu Li
    • , Da-Gang Yu
    • , Miao Yu
    • , Xiao Zhou
    • , Xing-Yu Lu
    • , Kun Huang
    • , Bi-Jie Li
    •  & Zhang-Jie Shi
  2. Department of Chemistry and Materials Science, Sichuan Normal University, Chengdu, Sichuan 610068, China

    • Shu-Fang Zheng

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Contributions

Z.-J.S. conceived the project. C.-L.S., H.L. and D.-G.Y. performed the experiments and analysed the data and contributed equally to this work. M.Y., X.Z., X.-Y.L., K.H. and S.-F.Z. worked on product isolation and purification. C.-L.S., B.-J.L. and Z.-J.S. wrote the paper. C.-L.S. wrote the Supplementary Information and contributed other related materials.

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The authors declare no competing financial interests.

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Correspondence to Zhang-Jie Shi.

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https://doi.org/10.1038/nchem.862

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