Computational analysis of site differences in selective aliphatic C-H hydroxylation by nonheme iron-oxo complexes

Selective C-H hydroxylation by nonheme iron complexes offers a promising method in the field of organic synthesis. Aliphatic C-H bond oxidation reactions of pivalate (R) catalyzed by [Fe(S,S-PDP)(CH₃CN)₂]²⁺ (CAT1) were examined using the density functional theory. Our calculations of the CH₃CN solvent agree with the experimental findings. However, it was observed that the gas-phase results did not replicate selective C-H hydroxylation observed experimentally when CAT1 catalyzed hydrocarbon oxidations by H₂O₂via an HO-Fe^V[double bond, length as m-dash]O oxidant (CAT1a). We inferred that the difference was mainly from hydrogen bonding formation, (CAT1a) O-HO[double bond, length as m-dash]C (R), in certain gaseous H-abstraction transition states (TS_H). Then, the appearance of the stronger (CAT1a) O-HN[triple bond, length as m-dash]CCH₃-solvent weakened the aforementioned interaction, leading to C-H activation influenced primarily by their electronic and steric properties. Such a deduction explained the same selective C-H found in both phases of reactions with CAT1b, a cyclic ferric peracetate oxidant, by the reason of TS_H without the influence of H-bonding. Another interesting finding was that the commonly recognized radical intermediate was further isomerized by a favorable electron rearrangement. Thus, the subsequent OH-rebound behavior proceeded by an electrostatic interaction. This study provides mechanistic clues for modifying regioselective C-H hydroxylation for molecule synthesis applications.