Cobalt-Catalyzed C4-Selective Direct Alkylation of Pyridines

Authors

  • Dr. Takashi Andou,

    1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Yutaka Saga,

    1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    2. JST, ERATO, Kanai Life Science Catalysis Project, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Hirotomo Komai,

    1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    2. JST, ERATO, Kanai Life Science Catalysis Project, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    Search for more papers by this author
  • Dr. Shigeki Matsunaga,

    Corresponding author
    1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    2. JST, ACT-C, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    Search for more papers by this author
  • Prof. Dr. Motomu Kanai

    Corresponding author
    1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    2. JST, ERATO, Kanai Life Science Catalysis Project, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    Search for more papers by this author

  • We thank Mr. Shohei Yamamoto for fruitful discussions and experimental support. This work was supported in part by ERATO from JST (M.K.), a Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Activation Directed toward Straightforward Synthesis” from MEXT (S.M.), the ACT-C program from JST (S.M.) and the Naito Foundation. T.A. thanks JSPS for a postdoctoral fellowship.

Abstract

original image

How pyridine got its tail: A new catalyst for the atom-economical C4-selective direct alkylation of pyridines is described. A combination of CoBr2 and LiBEt3H catalyzes the reaction of pyridines with 1-alkenes at 70 °C to give alkylation products with C4/C2 ratios of >20:1. Substrate/catalyst ratios of up to 4000, and a turnover number of 3440 were achieved.

Ancillary