Aromatic C–F Hydroxylation by Nonheme Iron(IV)–Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations

The synthesis and reactivity of a series of mononuclear nonheme iron complexes that carry out intramolecular aromatic C–F hydroxylation reactions is reported. The key intermediate prior to C–F hydroxylation, [FeIV(O)­(N4Py2Ar1 )]­(BF4)2 (1-O, Ar1 = −2,6-difluorophenyl), was characterized by single-crystal X-ray diffraction. The crystal structure revealed a nonbonding C–H···OFe interaction with a CH3CN molecule. Variable-field Mössbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The Mössbauer parameters for 1-O include an unusually small quadrupole splitting for a triplet FeIV(O) and are reproduced well by density functional theory calculations. With the aim of investigating the initial step for C–F hydroxylation, two new ligands were synthesized, N4Py2Ar2 (L2, Ar2 = −2,6-difluoro-4-methoxyphenyl) and N4Py2Ar3 (L3, Ar3 = −2,6-difluoro-3-methoxyphenyl), with −OMe substituents in the meta or ortho/para positions with respect to the C–F bonds. FeII complexes [Fe­(N4Py2Ar2 )­(CH3CN)]­(ClO4)2 (2) and [Fe­(N4Py2Ar3 )­(CH3CN)]­(ClO4)2 (3) reacted with isopropyl 2-iodoxybenzoate to give the C–F hydroxylated FeIII–OAr products. The FeIV(O) intermediates 2-O and 3-O were trapped at low temperature and characterized. Complex 2-O displayed a C–F hydroxylation rate similar to that of 1-O. In contrast, the kinetics (via stopped-flow UV–vis) for complex 3-O displayed a significant rate enhancement for C–F hydroxylation. Eyring analysis revealed the activation barriers for the C–F hydroxylation reaction for the three complexes, consistent with the observed difference in reactivity. A terminal FeII(OH) complex (4) was prepared independently to investigate the possibility of a nucleophilic aromatic substitution pathway, but the stability of 4 rules out this mechanism. Taken together the data fully support an electrophilic C–F hydroxylation mechanism.