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

Nature Chemistry volume 2, pages 1044–1049 (2010)Cite this article

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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.

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Figure 1: Direct aromatic C–H transformations.
Figure 2: Kinetic studies comparing the reaction profile with various added transition-metal catalysts.
Figure 3: Metal-free process in the intramolecular cross-coupling to prepare 6H-benzo[c]chromene.
Figure 4: Proposed interactions between the phenanthroline, base and substrate for this transition metal-free cross-coupling.

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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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Authors and 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, 610068, Sichuan, 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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Correspondence to Zhang-Jie Shi.

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Sun, CL., Li, H., Yu, DG. et al. An efficient organocatalytic method for constructing biaryls through aromatic C–H activation. Nature Chem 2, 1044–1049 (2010). https://doi.org/10.1038/nchem.862

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