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

Abstract

ABSTRACT 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 (O 2 )(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.