<i>cis</i>-Dihydroxylation by Synthetic Iron(III)–Peroxo Intermediates and Rieske Dioxygenases: Experimental and Theoretical Approaches Reveal the Key O–O Bond Activation Step

Dioxygen (O₂) activation by iron-containing enzymes and biomimetic compounds generates iron-oxygen intermediates, such as iron-superoxo, -peroxo, -hydroperoxo, and -oxo, that mediate oxidative reactions in biological and abiological systems. Among the iron-oxygen intermediates, iron(III)-peroxo species are less frequently implicated as active intermediates in oxidation reactions. In this study, we present the combined experimental and theoretical investigations on <i>cis</i>-dihydroxylation reactions mediated by synthetic mononuclear nonheme iron-peroxo intermediates, demonstrating the importance of supporting ligands and metal centers in activating the peroxo ligand toward the O-O bond homolysis for the <i>cis</i>-dihydroxylation reactions. We found a significant ring size effect of the TMC ligand in [Fe^III(O₂)(<i>n</i>-TMC)]⁺ (TMC = tetramethylated tetraazacycloalkane; <i>n</i> = 12, 13, and 14) on the <i>cis</i>-dihydroxylation reactivity order: [Fe^III(O₂)(12-TMC)]⁺ > [Fe^III(O₂)(13-TMC)]⁺ > [Fe^III(O₂)(14-TMC)]⁺. Additionally, we found that only [Fe^III(O₂)(<i>n</i>-TMC)]⁺, but not other metal-peroxo complexes such as [M^III(O₂)(<i>n</i>-TMC)]⁺ (M = Mn, Co, and Ni), is reactive for the <i>cis</i>-dihydroxylation of olefins. Using density functional theory (DFT) calculations, we revealed that electron transfer from the Fe d_<i>xz</i> orbital to the peroxo σ*(O-O) orbital facilitates the O-O bond homolysis, with the O-O bond cleavage barrier well correlated with the energy gap between the frontier molecular orbitals of d_<i>xz</i> and σ*(O-O). Further computational studies showed that the reactivity of the synthetic [Fe^III(O₂)(12-TMC)]⁺ complex is comparable to that of Rieske dioxygenases in <i>cis</i>-dihydroxylation, providing compelling evidence of the potential involvement of Fe(III)-peroxo species in Rieske dioxygenases. Thus, the present results significantly advance our understanding of the <i>cis</i>-dihydroxylation mechanisms by Rieske dioxygenases and synthetic nonheme iron-peroxo models.