Selective N-Alkylation of Indoles with α,β-Unsaturated Compounds Catalyzed by a Monomeric Phosphate

Authors

  • Hanako Sunaba,

    1. Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan), Fax: (+81) 3-5841-7220
    Search for more papers by this author
  • Dr. Keigo Kamata,

    1. Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan), Fax: (+81) 3-5841-7220
    Search for more papers by this author
  • Prof. Dr. Noritaka Mizuno

    Corresponding author
    1. Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan), Fax: (+81) 3-5841-7220
    • Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan), Fax: (+81) 3-5841-7220

    Search for more papers by this author

Abstract

Catalytic N-alkylation of indoles is challenging because the N1 nitrogen atoms are inert toward electrophilic reagents. Herein, an organic-solvent-soluble alkylammonium salt of a simple monomeric phosphate ion, [PO4]3−, with a high charge density acts as an efficient homogeneous catalyst for selective N-alkylation of indoles with α,β-unsaturated compounds. For the reaction of indole with ethyl acrylate, the turnover number reached up to 36 and the turnover frequency was 216 h−1; these values are the highest among those reported for base-mediated systems so far. In the presence of [PO4]3− ions, various combinations of nitrogen nucleophiles (ten examples) and α,β-unsaturated compounds (four examples) were efficiently converted to the desired N-alkylated products in high yields. NMR and IR spectroscopies showed formation of the indolyl anion through the activation of indole by the [PO4]3− ion, which plays an important role in the present N-alkylation.

Ancillary