Theoretical studies of the reaction mechanism of iron(III) catalyzed synthesis of 3-amidoindole from 2-arylindoles

Iron(III) trifluoromethansulfonate [Fe(OTf)₃] was explored experimentally to catalyze coupling reaction between phenylhydrazine and 2- phenylindole with TBN as additive and DCE as solvent, giving moderate to excellent yields. A reaction mechanism was proposed from experimental conclusions derived from different reaction conditions, mainly including [1,5]-hydrogen migration, coordination reaction, nucleophilic addition reaction and charge transfer. Reactants, proposed reaction intermediates and products were modeled with density functional theory (DFT) using B3LYP functional with 6-311+G(d,p) basis set by the Gaussian 16 quantum chemical package. Initially, the substituent on indole and hydrazine were changed from phenyl group to methyl groups for preliminary investigation. Relative energies of reaction intermediates were evaluated to determine the thermodynamic feasibility of each reaction step. In case of encountering chemically unreasonable barrier, alternative reaction pathway was explored. The main objective is to understand the role of Fe(OTf)₃ in activating the C-3 position of indole for the nucleophilic attack by hydrazine. Finally, solvent effect will be explored to explain the preference of dichloroethane over ethanol, tetrahydrofuran and methyl cyanide for the coupling Reaction.