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A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate

Nature Chemistry volume 7, pages 712–717 (2015)Cite this article

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Abstract

Regioselective C–H bond transformations are potentially the most efficient method for the synthesis of organic molecules. However, the presence of many C–H bonds in organic molecules and the high activation barrier for these reactions make these transformations difficult. Directing groups in the reaction substrate are often used to control regioselectivity, which has been especially successful for the ortho-selective functionalization of aromatic substrates. Here, we describe an iridium-catalysed meta-selective C–H borylation of aromatic compounds using a newly designed catalytic system. The bipyridine-derived ligand that binds iridium contains a pendant urea moiety. A secondary interaction between this urea and a hydrogen-bond acceptor in the substrate places the iridium in close proximity to the meta-C–H bond and thus controls the regioselectivity. 1H NMR studies and control experiments support the participation of hydrogen bonds in inducing regioselectivity. Reversible direction of the catalyst through hydrogen bonds is a versatile concept for regioselective C–H transformations.

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Figure 1: meta-Selective C–H transformations.
Figure 2: Concept of regioselective C–H transformations controlled by a hydrogen-bonding secondary interaction between ligand and substrate.
Figure 3: Mechanistic support for the importance of hydrogen bonding between the catalyst and substrates in controlling regioselectivity.

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Acknowledgements

This work was supported in part by ERATO from the Japan Science and Technology Agency and by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Yoichiro Kuninobu, Haruka Ida, Mitsumi Nishi & Motomu Kanai

  2. ERATO, Japan Science and Technology Agency (JST), Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Yoichiro Kuninobu, Mitsumi Nishi & Motomu Kanai

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  1. Yoichiro Kuninobu
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  2. Haruka Ida
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Contributions

Y.K. conceived and designed the experiments and ligands, and prepared the manuscript. H.I. and M.N. performed the experiments. Y.K. and M.K. directed the project. All authors discussed the results and commented on the manuscript.

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Correspondence to Yoichiro Kuninobu or Motomu Kanai.

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The authors declare no competing financial interests.

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Kuninobu, Y., Ida, H., Nishi, M. et al. A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate. Nature Chem 7, 712–717 (2015). https://doi.org/10.1038/nchem.2322

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