10-Fold Increase in Hydrogen Atom Transfer Reactivity for a Series of S = 1 FeIV═O Complexes Over the S = 2 [(TQA)FeIV═O]2+ Complex via Entropic Lowering of Reaction Barriers by Secondary Sphere Cycloalkyl Substitution

Abstract

Nonheme iron enzymes utilize S = 2 iron(IV)-oxo intermediates as oxidants in biological oxygenations. In contrast, corresponding synthetic nonheme Fe^IV═O complexes characterized to date favor the S = 1 ground state that generally shows much poorer oxidative reactivity than their S = 2 counterparts. However, one intriguing exception found by Nam a decade ago is the S = 1 [Fe^IV(O)(Me₃NTB)]²⁺ complex (Me₃NTB = [tris((N-methyl-benzimidazol-2-yl)methyl)amine], 1O) with a hydrogen atom transfer (HAT) reactivity that is 70% that of the S = 2 [Fe^IV(O)(TQA)]²⁺ complex (TQA = tris(2-quinolylmethyl)amine, 3O). In our efforts to further explore this direction, we have unexpectedly uncovered a family of new S = 1 complexes with HAT reaction rates beyond the currently reported limits in the tripodal ligand family, surpassing oxidation rates found for the S = 2 [Fe^IV(O)(TQA)]²⁺ complex by as much as an order of magnitude. This is achieved simply by replacing the secondary sphere methyl groups of the Me₃NTB ligand with larger cycloalkyl-CH₂ (R groups in 2O^R) moieties ranging from c-propylmethyl to c-hexylmethyl. These 2O^R complexes show Mössbauer data at 4 K and ¹H NMR spectra at 193 and 233 K that reveal S = 1 ground states, in line with DFT calculations. Nevertheless, they give rise to the most reactive synthetic nonheme oxoiron(IV) complexes found to date within the tripodal ligand family. Our DFT study indicates transition state stabilization through entropy effects, similar to enzymatic catalysis.

Figure 1.

ORTEP plots of complex cation of (a) 2^c-propyl, (b) 2^oxanyl and (c) 2^c-hexyl with 40% thermal ellipsoid parameters and all the H-atoms omitted for clarity.

Figure 2.

Decay of 1.0 mM 2O^c-propyl, generated from 2^c-propyl with ^SArIO in CH₃CN at 233 K. Inset: time trace for the band at 772 nm.

Figure 3.

Plot of k_obs (at 233 K) vs concentration of toluene for the reaction with 2O^c-propyl (red line), 2O^c-butyl (blue line), 2O^c-pentyl (purple line), 2O^c-hexyl (olive line), 2O^adamantyl (pink line), 2O^oxanyl (orange line).

Figure 4.

Plot of logk₂’ (at 233 K) vs. the C–H BDE of substrates in the reaction of 1O (black line), 2O^c-propyl (red line), 2O^c-butyl (blue line), 2O^c-pentyl (sky line), 2O^c-hexyl (olive line), 2O^adamantyl (purple line), 2O^oxanyl (pink line), and 3O (grey line) with various substrates. The k₂’ values are calculated from the second-order rate constant of substrate oxidation reactions (k₂). The k₂ values for the entire series of substrates from Figures S23–S28 are listed in Table S8 in the SI (error bars are also listed in Table S8).

Figure 5.

The ¹H NMR spectra of 2O^R complexes (24 to 10 ppm) in acetone-d₆ at 193 K.

Figure 6.

Electronic energy profiles (kJ·mol⁻¹, S12g/TZ2P) for reactions of Fe(IV)=O complexes with TQA, Me₃NTB and (R-CH₂)₃NTB (R = cyclohexyl) ligands. In the latter two cases two-state reactivity is observed. The spin states of the given optimized figures are as follows: for 3O, RC, TS, PC (S = 2); for 1O and 2O^c-hexyl, RC (S = 1) and TS and PC (S = 2).

Figure 7.

Plots of cyclohexane oxidation rates of [{(R-CH₂)₃NTB}Fe^IV(O)(CH₃CN)]²⁺ complexes (a) vs the ring size of the corresponding R groups and (b) vs the ring strain energy of the corresponding R groups.

Figure 8.

Figure of 2O^c-hexyl which shows the H atoms that are contributing most to the change in S_vib along the reaction pathway.

Figure 9.

Overlay of the S12g/TZ2P Fe^IV=O structures with simple cycloalkyls (top), 1O, 3O, 2O^oxanyl and 2O^adamantyl (bottom). Highlighted in green (top) and red (bottom) are 2O^c-hexyl and 2O^adamantyl, respectively.

Figure 10.

Comparison of k₂ values of toluene oxidation rates for [{(R-CH₂)₃NTB}Fe^IV(O)(CH₃CN)]²⁺ complexes at 233 K with other previously reported very reactive synthetic iron(IV)-oxo molecules.

Scheme 1.

Iron(IV)-Oxo Complexes Discussed in This Work (L represents the acetonitrile solvent). The labeling protocol for protons on the benzimidazole rings used is shown for 2O^R.