title: Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations.
abstract: 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. FeIIcomplexes [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.
authors.affiliation: Department of Chemistry, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sahu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pollock
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg , 91058 Erlangen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Dürr
authors.affiliation: Department of Chemistry & MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Otago , PO Box 56, Dunedin 9054, New Zealand.
authors.forename: Casey G
authors.initials: CG
authors.lastname: Davies
authors.affiliation: Department of Chemistry, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Confer
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg , 91058 Erlangen, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanović-Burmazović
authors.affiliation: Department of Chemistry, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Maxime A
authors.initials: MA
authors.lastname: Siegler
authors.affiliation: Department of Chemistry & MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Otago , PO Box 56, Dunedin 9054, New Zealand.
authors.forename: Guy N L
authors.initials: GN
authors.lastname: Jameson
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.affiliation: Department of Chemistry, The Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Goldberg