Tunneling Effect That Changes the Reaction Pathway from Epoxidation to Hydroxylation in the Oxidation of Cyclohexene by a Compound I Model of Cytochrome P450

Abstract

The rate constants of the C═C epoxidation and the C-H hydroxylation (i.e., allylic C-H bond activation) in the oxidation of cyclohexene by a high-valent iron(IV)-oxo porphyrin π-cation radical complex, [(TMP)Fe(O)(Cl)] (1, TMP = meso-tetramesitylporphyrin dianion), were determined at various temperatures by analyzing the overall rate constants and the products obtained in the cyclohexene oxidation by 1, leading us to conclude that reaction pathway changes from the C═C epoxidation to C-H hydroxylation by decreasing reaction temperature. When cyclohexene was replaced by deuterated cyclohexene (cyclohexene-d), the epoxidation pathway dominated irrespective of the reaction temperature. The temperature dependence of the rate constant of the C-H hydroxylation pathway in the reactions of cyclohexene and cyclohexene-d by 1 suggests that there is a significant tunneling effect on the hydrogen atom abstraction of allylic C-H bonds of cyclohexene by 1, leading us to propose that the tunneling effect is a determining factor for the switchover of the reaction pathway from the C═C epoxidation pathway to the C-H hydroxylation pathway by decreasing reaction temperature. By performing density functional theory (DFT) calculations, the reaction energy barriers of the C═C epoxidation and C-H bond activation reactions by 1 were found to be similar, supporting the notion that small environmental changes, such as the reaction temperature, can flip the preference for one reaction to another.

Structure and spin state of nonheme FeIVO complexes depending on temperature: predictive insights from DFT calculations and experiments

“…This vertical energy difference has the potential to change the energy barriers of an HAT reaction. 26 We found in this and a parallel study 27 that the energy barrier difference in the HAT reaction when using these two C–H bonds is around 2 kcal mol –1 (see Tables S2 and S4, ESI † ). Hence, the number of equivalent C–H bonds in cyclohexene is not 4 but 2, and it is potentially important to choose the “right” C–H bonds for calculations.…”

Large Isotope Effects in Organometallic Chemistry

“…[134,135] Methane monooxygenase [136] operates with large KIEs and has served as inspiration for functional synthetic model complexes. Synthetic inorganic iron heme [45,50,[137][138][139][140] and nonheme [44,49,[141][142][143] compounds, along with other metal oxo complexes [51,52,[144][145][146][147][148][149][150][151][152] , have been found to activate CÀ H bonds with large isotope effects, which are often ascribed to tunneling. Catalytic CÀ H amination by an iron imido complex, and stoichiometric CÀ H amination by a diruthenium nitride site in a metal-organic framework (MOF), have been reported and attributed to tunneling.…”

Deuterium kinetic isotope effects as redox mechanistic criterions

“…34 Strong tunneling effects have also been reported in C H bond activation reactions by high-valent metal-oxo species such as Fe IV -oxo and Fe V -oxo complexes. [68][69][70][71][72][73][74][75][76][77][78][79][80] A large tunneling effect on the hydrogen evolution in the decomposition of formic acid (HC(═O)OH, DC(═O)OH, or DC(═O)OD) catalyzed by a heterodinuclear Ir(III)-Ru(II) complex [Ir III (Cp * )(H 2 O)(bpm)-Ru II (bpy) 2 ](SO 4 ) 2 (Cp * = Me 5 -cyclopentadienyl, bpm = 2,2 0 -bipyrimidine, and bpy = 2,2 0 -bipyridine) in H 2 O and D 2 O has been reported. 81 The Arrhenius plots of the turnover frequencies in D 81 The H/D exchange reactions between formic acid and D 2 O were also found to involve a quantum tunneling effect, as evidenced by the large KIE value.…”