Ruthenium(II)-Catalyzed Synthesis of Pyrrole- and Indole-Fused Isocoumarins by C-H Bond Activation in DMF and Water

Pyrrole- and indole-fused isocoumarins constitute important structural units in natural products and pharmacophores, although the direct and selective bifunctionalization of pyrrole and indole remain a challenge. Herein, we report a one-pot synthesis of pyrrole- and indole-fused isocoumarins from simple 1-methylpyrrole-2-carboxylic acid and 1-methylindole-3-carboxylic acid by annulation with alkynes in the presence of a ruthenium(II) catalyst based on [RuCl2(p-cymene)](2) with Cu(OAc)(2)H2O as the oxidant in DMF. This ruthenium(II)-catalyzed transformation was shown to be profitably performed in water as the solvent. The reaction, which involves carboxylate coordination, activation of the heterocyclic sp(2) C-H bond, and insertion of the alkyne, is regioselective, which leads to good yields of the isocoumarins.