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

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, [PO 4 ] 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 [PO 4 ] 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 [PO 4 ] 3− ion, which plays an important role in the present N‐alkylation.