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

Sumit Sahu, Bo Zhang, Christopher J. Pollock, Maximilian Dürr, Casey G. Davies, Alex M. Confer, Ivana Ivanović-Burmazović, Maxime A. Siegler, Guy N.L. Jameson, Carsten Krebs, David P. Goldberg

Research output: Contribution to journalArticle

21 Citations (Scopus)

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)(N4Py2Ar 1)](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, N4Py2Ar 2(L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar 3(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(N4Py2Ar 2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar 3)(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.

Original languageEnglish (US)
Pages (from-to)12791-12802
Number of pages12
JournalJournal of the American Chemical Society
Volume138
Issue number39
DOIs
StatePublished - Oct 5 2016

Fingerprint

Hydroxylation
Iron
Activation Analysis
ferryl iron
X-Ray Diffraction
Ground state
Density functional theory
Spectrum Analysis
Substitution reactions
Crystal structure
Chemical activation
Ligands
Single crystals
Spectroscopy
X ray diffraction
Molecules
Kinetics
Temperature

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Sahu, S., Zhang, B., Pollock, C. J., Dürr, M., Davies, C. G., Confer, A. M., ... Goldberg, D. P. (2016). Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations. Journal of the American Chemical Society, 138(39), 12791-12802. https://doi.org/10.1021/jacs.6b03346
Sahu, Sumit ; Zhang, Bo ; Pollock, Christopher J. ; Dürr, Maximilian ; Davies, Casey G. ; Confer, Alex M. ; Ivanović-Burmazović, Ivana ; Siegler, Maxime A. ; Jameson, Guy N.L. ; Krebs, Carsten ; Goldberg, David P. / Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes : Structural, Spectroscopic, and Mechanistic Investigations. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 39. pp. 12791-12802.
@article{28da64d3c0e845ffae11211c63626487,
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)(N4Py2Ar 1)](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 M{\"o}ssbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The M{\"o}ssbauer 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, N4Py2Ar 2(L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar 3(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(N4Py2Ar 2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar 3)(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.",
author = "Sumit Sahu and Bo Zhang and Pollock, {Christopher J.} and Maximilian D{\"u}rr and Davies, {Casey G.} and Confer, {Alex M.} and Ivana Ivanović-Burmazović and Siegler, {Maxime A.} and Jameson, {Guy N.L.} and Carsten Krebs and Goldberg, {David P.}",
year = "2016",
month = "10",
day = "5",
doi = "10.1021/jacs.6b03346",
language = "English (US)",
volume = "138",
pages = "12791--12802",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "39",

}

Sahu, S, Zhang, B, Pollock, CJ, Dürr, M, Davies, CG, Confer, AM, Ivanović-Burmazović, I, Siegler, MA, Jameson, GNL, Krebs, C & Goldberg, DP 2016, 'Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations', Journal of the American Chemical Society, vol. 138, no. 39, pp. 12791-12802. https://doi.org/10.1021/jacs.6b03346

Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes : Structural, Spectroscopic, and Mechanistic Investigations. / Sahu, Sumit; Zhang, Bo; Pollock, Christopher J.; Dürr, Maximilian; Davies, Casey G.; Confer, Alex M.; Ivanović-Burmazović, Ivana; Siegler, Maxime A.; Jameson, Guy N.L.; Krebs, Carsten; Goldberg, David P.

In: Journal of the American Chemical Society, Vol. 138, No. 39, 05.10.2016, p. 12791-12802.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes

T2 - Structural, Spectroscopic, and Mechanistic Investigations

AU - Sahu, Sumit

AU - Zhang, Bo

AU - Pollock, Christopher J.

AU - Dürr, Maximilian

AU - Davies, Casey G.

AU - Confer, Alex M.

AU - Ivanović-Burmazović, Ivana

AU - Siegler, Maxime A.

AU - Jameson, Guy N.L.

AU - Krebs, Carsten

AU - Goldberg, David P.

PY - 2016/10/5

Y1 - 2016/10/5

N2 - 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)(N4Py2Ar 1)](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, N4Py2Ar 2(L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar 3(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(N4Py2Ar 2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar 3)(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.

AB - 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)(N4Py2Ar 1)](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, N4Py2Ar 2(L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar 3(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(N4Py2Ar 2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar 3)(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.

UR - http://www.scopus.com/inward/record.url?scp=84990042043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990042043&partnerID=8YFLogxK

U2 - 10.1021/jacs.6b03346

DO - 10.1021/jacs.6b03346

M3 - Article

AN - SCOPUS:84990042043

VL - 138

SP - 12791

EP - 12802

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 39

ER -