Janus Reactivity of a Mononuclear Non-Heme Iron(III)-Peroxo Complex Toward Indole Oxidation

Indole oxidation reaction is a pivotal process in organic chemistry, playing a crucial role in the synthesis of various natural products and pharmaceuticals. To-date, indole oxidation is limited to heme enzymes and synthetic iron porphyrin compounds. Herein, we demonstrate its efficient execution in a nonheme iron system. We report the oxidation of a broad range of indole substrates by a mononuclear nonheme iron(III)-peroxo complex, [Fe^III(O₂)(12-TMC)]⁺ (1), to their corresponding dioxygenated products. A significant kinetic isotope effect of 5.2 is determined in the reactions of 1 with N─H and N-D 2,3-dimethylindoles, thereby supporting an N─H hydrogen atom abstraction (HAT) mechanism. Interestingly, an alternative mechanism involving electrophilic addition of the iron-peroxo group to the C2-C3 double bond of the indole ring to form iron-cycloadduct products predominates when N-methylated indoles are used as substrates. Theory supports the observed bifurcation reaction pathways, such as the N─H HAT and the C2-C3 double bond addition. Whether such bifurcation pathways have any role in determining the selectivity of biological indole oxidation reactions by heme-dependent dioxygenases is now an inherent question, which should be investigated in future studies.