Chemoselectivity in the Oxidation of Cycloalkenes with a Non-Heme Iron(IV)-Oxo-Chloride Complex: Epoxidation vs. Hydroxylation Selectivity

Thibault Terencio,Ilaria Gamba,Miquel Costas,Erik Andris,Martin Srnec,Jana Roithová

doi:10.1007/s13361-019-02251-1

Abstract

We report and analyze chemoselectivity in the gas phase reactions of cycloalkenes (cyclohexene, cycloheptene, cis-cyclooctene, 1,4-cyclohexadiene) with a non-heme iron(IV)-oxo complex [(PyTACN)Fe(O)(Cl)]+, which models the active species in iron-dependent halogenases. Unlike in the halogenases, we did not observe any chlorination of the substrate. However, we observed two other reaction pathways: allylic hydrogen atom transfer (HAT) and alkene epoxidation. The HAT is clearly preferred in the case of 1,4-cyclohexadiene, both pathways have comparable reaction rates in reaction with cyclohexene, and epoxidation is strongly favored in reactions with cycloheptene and cis-cyclooctene. This preference for epoxidation differs from the reactivity of iron(IV)-oxo complexes in the condensed phase, where HAT usually prevails. To understand the observed selectivity, we analyze effects of the substrate, spin state, and solvation. Our DFT and CASPT2 calculations suggest that all the reactions occur on the quintet potential energy surface. The DFT-calculated energies of the transition states for the epoxidation and hydroxylation pathways explain the observed chemoselectivity. The SMD implicit solvation model predicts the relative increase of the epoxidation barriers with solvent polarity, which explains the clear preference of HAT in the condensed phase.

Highlights

Iron(IV)-oxo compounds mediate diverse enzymatic oxidations including hydroxylation and halogenation of aliphatic C–H bonds, and epoxidation of alkenes and arenes [1,2,3,4,5,6,7,8,9,10]
Because the [(PyTACN)Fe(O)(Cl)]+ complex contains cisFeIV(O)(Cl) motif present in non-heme iron-dependent halogenases, we hypothesized that the complex will react with the substrate via an initial hydrogen atom transfer followed by chlorine rebound
9.2 ± 0.8 5.1 ± 1.3a akDAT = (0.90 ± 0.23) × 10−12 cm3 s−1 bThe rate constant was normalized against the known rate constant for the reaction of [(PyTACN)Fe(O)(NO3)]+ cations generated by the nitrate cleavage with 1,4cyclohexadiene-(1,2,3,4,5,6)-d6 ((13.9 ± 1.4) × 10−12 cm3 s−1) [64]

Summary

Introduction

Iron(IV)-oxo compounds mediate diverse enzymatic oxidations including hydroxylation and halogenation of aliphatic C–H bonds, and epoxidation of alkenes and arenes [1,2,3,4,5,6,7,8,9,10]. Hallmark reactions among these are hydroxylations mediated by the iron(IV)-oxo porphyrin radical (Cpd I) of heme iron enzymes, such as cytochrome P450 [11,12,13], which received considerable. Additional factors that have been suggested to govern the C–H vs. C=C selectivity include spin inversion probability [38] and the spin state of the iron complex [41]

Methods

Results

Discussion

Conclusion