Observation of Fe(V)=O using variable-temperature mass spectrometry and its enzyme-like C–H and C=C oxidation reactions

Journal name:
Nature Chemistry
Volume:
3,
Pages:
788–793
Year published:
DOI:
doi:10.1038/nchem.1132
Received
Accepted
Published online

Abstract

Oxo-transfer chemistry mediated by iron underpins many biological processes and today is emerging as synthetically very important for the catalytic oxidation of C–H and C=C moieties that are hard to activate conventionally. Despite the vast amount of research in this area, experimental characterization of the reactive species under catalytic conditions is very limited, although a Fe(V)=O moiety was postulated. Here we show, using variable-temperature mass spectrometry, the generation of a Fe(V)=O species within a synthetic non-haem complex at −40 °C and its reaction with an olefin. Also, with isotopic labelling we were able both to follow oxygen-atom transfer from H2O2/H2O through Fe(V)=O to the products and to probe the reactivity as a function of temperature. This study pioneers the implementation of variable-temperature mass spectrometry to investigate reactive intermediates.

At a glance

Figures

  1. Mechanistic proposals for the formation of formally oxo-iron(V) species.
    Figure 1: Mechanistic proposals for the formation of formally oxo-iron(V) species.

    a, Rieske dioxygenases (non-haem enzyme). b, Cytochrome P450 (haem enzyme). P refers to the (hydro)peroxide type of species (also known as compound 0 in cytochrome P450) and O refers to the formally oxo-iron(V) species (in the case of cytochrome P450, this compound is best described as an oxo-Fe(IV)-porphyrin radical cation, and is known as compound I). His = histidine, Asp = aspartate anion.

  2. Complex 1 catalyses the hydroxylation of alkanes and the cis-dihydroxylation of alkenes.
    Figure 2: Complex 1 catalyses the hydroxylation of alkanes and the cis-dihydroxylation of alkenes.

    a,b, Stereospecific hydroxylation of cis-1,2-dimethylcyclohexane (1,000 equiv.) (a) and epoxidation and cis-dihydroxylation of 2-heptene (1,000 equiv.) (b) with H2O2 (10 equiv.) catalysed by 1 in the presence of H218O (1,000 equiv.).

  3. Change of intensity of 3O or 3P when the temperature is increased from −40 °C to 20 °C.
    Figure 3: Change of intensity of 3O or 3P when the temperature is increased from −40 °C to 20 °C.

    a, The decrease in the normalized intensity of the peak at 486.1 m/z as the temperature increases provides evidence that 3O or 3P is the metastable intermediate, as these species are not observable at higher temperatures. b, Structure of {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) and {[Fe(III)(OOH)(Me,HPytacn)](OTf)}+ (3P).

  4. Mechanisms and shift of mass spectral peaks when H218O and H218O2 are used to give the Fe(V)(O)(OH) species.
    Figure 4: Mechanisms and shift of mass spectral peaks when H218O and H218O2 are used to give the Fe(V)(O)(OH) species.

    a, The formation of the oxo-iron(V) species {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) via a water-assisted heterolytic cleavage of the O–O bond in {[Fe(III)(OOH)(OH2)(Me,HPytacn)](OTf)}+ (3P·H2O). b, Cryospray ionization mass spectra (CSI-MS) of the species formed when [Fe(II)(Me,HPytacn)(OTf)2] (1) was reacted with H2O2 and H2O in acetonitrile solution at −40 °C. i, {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) generated with H216O2 (10 equiv.) in the presence of H216O (1,000 equiv.). ii, {[Fe(V)(O)(18OH)(Me,HPytacn)](OTf)}+ (3Oa) (the additional descriptor a refers to the isotopic composition of H2O and H2O2 reagents used in the generation of 3O) generated with H216O2 (10 equiv.) in the presence of H218O (1,000 equiv.). iii, {[Fe(V)(18O)(OH)(Me,HPytacn)](OTf)}+ (3Ob) generated with H218O2 (10 equiv.) in the presence of H216O (1,000 equiv.). iv, {[Fe(V)(18O)(18OH)(Me,HPytacn)](OTf)}+ (3Oc) generated with H218O2 (10 equiv.) in the presence of H218O (1,000 equiv.). All calculated peaks fit the statistical treatment of experimental error. Red bars correspond to the simulated data (see Supplementary Information for the full analysis of the isotopic envelope) and black lines correspond to the experimental data. • = 18-labelled oxygen, a.u. = arbitrary units.

  5. Mechanisms and shift of mass spectral peaks when H218O and H218O2 are used to give the hydrogenglycolates 5 and the glycolates 4.
    Figure 5: Mechanisms and shift of mass spectral peaks when H218O and H218O2 are used to give the hydrogenglycolates 5 and the glycolates 4.

    a, The reaction between the oxo-iron(V) species {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) with an olefin to form the hydrogenglycolate species {[Fe(III)(C8H14(O)(OH))(Me,HPytacn)](OTf)}+ (5) and glycolate species [Fe(III)(C8H14O(O))(Me,HPytacn)]+ (4). b, CSI-MS spectra of the species formed when {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) was reacted with an olefin in acetonitrile solution at −40 °C. i, {[Fe(III)(C8H14(O)(OH))(Me,HPytacn)](OTf)}+ (5) formed by reaction of cyclooctene (100 equiv.) with {[Fe(V)(O)(OH)(Me,HPytacn)](OTf)}+ (3O) (generated with H216O2 (3 equiv.) in the presence of H216O (1,000 equiv.)). ii, {[Fe(III)(C8H14(O)(18OH))(Me,HPytacn)](OTf)}+ (5a) (the additional descriptor a refers to the isotopic composition of H2O and H2O2 reagents used in the generation of 3O, which in turn form 5) formed by reaction of cyclooctene (100 equiv.) with {[Fe(V)(O)(18OH)(Me,HPytacn)](OTf)}+ (3Oa) (generated with H216O2 (3 equiv.) in the presence of H218O (1,000 equiv.)). iii, {[Fe(III)(C8H14(18O)(OH))(Me,HPytacn)](OTf)}+ (5b) formed by reacting cyclooctene (100 equiv.) with {[Fe(V)(18O)(OH)(Me,HPytacn)](OTf)}+ (3Ob) (generated with H218O2 (3 equiv.) in the presence of H216O (1,000 equiv.)). iv, {[Fe(III)(C8H14(18O)(18OH))(Me,HPytacn)](OTf)}+ (5c) formed by reacting cyclooctene (100 equiv.) with {[Fe(V)(18O)(18OH)(Me,HPytacn)](OTf)}+ (3Oc) (generated with H218O2 (3 equiv.) in the presence of H218O (1,000 equiv.)).

  6. DFT Gibbs energy profile of the reaction between the oxo-iron(V) species 3O with trans-2-butene to form the hydrogenglycolate species 5.
    Figure 6: DFT Gibbs energy profile of the reaction between the oxo-iron(V) species 3O with trans-2-butene to form the hydrogenglycolate species 5.

    Hydrogen atoms on the olefin substrate are omitted for clarity (see Supplementary Methods S16 for full details on the computational methods). TS = transition state.

Compounds

30 compounds View all compounds
  1. [FeII(CF3SO3)2(Me,HPytacn)]
    Compound 1 [FeII(CF3SO3)2(Me,HPytacn)]
  2. {[FeV(O)(OH)(Me,HPytacn)](CF3SO3)}+
    Compound 3O {[FeV(O)(OH)(Me,HPytacn)](CF3SO3)}+
  3. {[FeV(O)(18OH)(Me,HPytacn)](CF3SO3)}+
    Compound 3Oa {[FeV(O)(18OH)(Me,HPytacn)](CF3SO3)}+
  4. {[FeV(18O)(OH)(Me,HPytacn)](CF3SO3)}+
    Compound 3Ob {[FeV(18O)(OH)(Me,HPytacn)](CF3SO3)}+
  5. {[FeV(18O)(18OH)(Me,HPytacn)](CF3SO3)}+
    Compound 3Oc {[FeV(18O)(18OH)(Me,HPytacn)](CF3SO3)}+
  6. {[FeIII(OOH)(Me,HPytacn)](CF3SO3)}+
    Compound 3P {[FeIII(OOH)(Me,HPytacn)](CF3SO3)}+
  7. [FeIII(C8H14O2)(Me,HPytacn)]+
    Compound 4 [FeIII(C8H14O2)(Me,HPytacn)]+
  8. [FeIII(C8H14O(18O))(Me,HPytacn)]+
    Compound 4a [FeIII(C8H14O(18O))(Me,HPytacn)]+
  9. [FeIII(C8H14(18O)O)(Me,HPytacn)]+
    Compound 4b [FeIII(C8H14(18O)O)(Me,HPytacn)]+
  10. [FeIII(C8H1418O2)(Me,HPytacn)]+
    Compound 4c [FeIII(C8H1418O2)(Me,HPytacn)]+
  11. {[FeIII(C8H14O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 5 {[FeIII(C8H14O(OH))(Me,HPytacn)](CF3SO3)}+
  12. {[FeIII(C8H14O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 5a {[FeIII(C8H14O(18OH))(Me,HPytacn)](CF3SO3)}+
  13. {[FeIII(C8H1418O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 5b {[FeIII(C8H1418O(OH))(Me,HPytacn)](CF3SO3)}+
  14. {[FeIII(C8H1418O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 5c {[FeIII(C8H1418O(18OH))(Me,HPytacn)](CF3SO3)}+
  15. [FeIII(C8H16O2)(Me,HPytacn)]+
    Compound 6 [FeIII(C8H16O2)(Me,HPytacn)]+
  16. [FeIII(C8H16O(18O))(Me,HPytacn)]+
    Compound 6a [FeIII(C8H16O(18O))(Me,HPytacn)]+
  17. [FeIII(C8H16(18O)O)(Me,HPytacn)]+
    Compound 6b [FeIII(C8H16(18O)O)(Me,HPytacn)]+
  18. [FeIII(C8H1618O2)(Me,HPytacn)]+
    Compound 6c [FeIII(C8H1618O2)(Me,HPytacn)]+
  19. {[FeIII(C8H16O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 7 {[FeIII(C8H16O(OH))(Me,HPytacn)](CF3SO3)}+
  20. {[FeIII(C8H16O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 7a {[FeIII(C8H16O(18OH))(Me,HPytacn)](CF3SO3)}+
  21. {[FeIII(C8H1618O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 7b {[FeIII(C8H1618O(OH))(Me,HPytacn)](CF3SO3)}+
  22. {[FeIII(C8H1618O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 7c {[FeIII(C8H1618O(18OH))(Me,HPytacn)](CF3SO3)}+
  23. [FeIII(C6H10O2)(Me,HPytacn)]+
    Compound 8 [FeIII(C6H10O2)(Me,HPytacn)]+
  24. [FeIII(C6H10O(18O))(Me,HPytacn)]+
    Compound 8a [FeIII(C6H10O(18O))(Me,HPytacn)]+
  25. [FeIII(C6H10(18O)O)(Me,HPytacn)]+
    Compound 8b [FeIII(C6H10(18O)O)(Me,HPytacn)]+
  26. [FeIII(C6H1018O2)(Me,HPytacn)]+
    Compound 8c [FeIII(C6H1018O2)(Me,HPytacn)]+
  27. {[FeIII(C6H10O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 9 {[FeIII(C6H10O(OH))(Me,HPytacn)](CF3SO3)}+
  28. {[FeIII(C6H10O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 9a {[FeIII(C6H10O(18OH))(Me,HPytacn)](CF3SO3)}+
  29. {[FeIII(C6H1018O(OH))(Me,HPytacn)](CF3SO3)}+
    Compound 9b {[FeIII(C6H1018O(OH))(Me,HPytacn)](CF3SO3)}+
  30. {[FeIII(C6H1018O(18OH))(Me,HPytacn)](CF3SO3)}+
    Compound 9c {[FeIII(C6H1018O(18OH))(Me,HPytacn)](CF3SO3)}+

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Author information

  1. These authors contributed equally to this work

    • Irene Prat &
    • Jennifer S. Mathieson

Affiliations

  1. Departament de Química, Universitat de Girona, Campus de Montilivi, Girona 17071, Spain

    • Irene Prat,
    • Mireia Güell,
    • Xavi Ribas,
    • Josep M. Luis &
    • Miquel Costas
  2. WestCHEM, School of Chemistry, The University of Glasgow, Glasgow G12 8QQ, UK

    • Jennifer S. Mathieson &
    • Leroy Cronin
  3. Institut de Química Computacional, Universitat de Girona, Campus de Montilivi, Girona 17071, Spain

    • Mireia Güell &
    • Josep M. Luis

Contributions

L.C. and M.C. devised the initial concept for the work, L.C., M.C., X.R., J.S.M., I.P., J.M.L. and M.G. designed the experiments and J.S.M., M.G. and I.P. carried out the experiments and analysed the data. M.C. and L.C. co-wrote the manuscript.

Competing financial interests

The authors declare no competing financial interests.

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