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Bio-Inspired Iron Complexes in Oxidation Reactions

Graduate Seminar

Indian Institute of Technology Kanpur

Department of Chemistry

Supervisor: Prof. Jitendra K. Bera

Khushboo Yadav

21107292

18^th August 2022

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Contents

• Introduction

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• Generation and Characterisation of high valent intermediate

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• Catalytic Activation of dioxygen by Iron complexes

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• Conclusion

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Methanemonooxygenase (MMO)

Cytochrome P450; X=Cys

Rieske dioxygenase

Natural occurring metalloenzymes

Nam et al. Chem. Soc. Rev., 2021, 50, 4806

α-keto acid-dependent oxygenase

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Importance of biomimicking

Que, Jr. et al. Angew. Chem. Int. Ed. 2020, 59, 7332

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Dioxygen activation

Karkas et al. Nat. Catal. 2021, 4, 96

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Common metal−oxygen intermediates

Nam et al. Chem. Soc. Rev., 2021, 50, 4807

Monometallic

Bimetallic

as superoxo ligand

as peroxo ligand

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UV−vis absorption spectra at -40^oC

Sc³⁺ promoted O−O bond cleavage to generate [Fe^IV₂(μ-O)₂]

Que, Jr. et al. J. Am. Chem. Soc. 2020, 142, 4285

⁵⁷Fe Mössbauer at 4.2 K

Fe(IV)

HS Fe(III)

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Characterization of [Fe^III₂(μ-O)(μ-1,2-O₂)]

Raman spectra of 2 at 77 K

Que, Jr. et al. J. Am. Chem. Soc. 2020, 142, 4285

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Characterization of [Fe^III₂(μ-OH)(μ-1,2-O₂)] & [Fe^IV₂(μ-O)₂]

Raman spectra of 4 at 233 K

Raman spectra of 3 at 4.2 K

Que, Jr. et al. J. Am. Chem. Soc. 2020, 142, 4285

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protonation goes after buried oxo bridge, but larger Sc³⁺ ion attack more accessible peroxo moiety

Proposed mechanism

oxo face

peroxo face

Que, Jr. et al. J. Am. Chem. Soc. 2020, 142, 4285

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Kovacs et al. J. Am. Chem. Soc. 2022, 144, 8515

Depiction of the Isopenicillin N synthase (IPNS) intermediate

cleavage of the cysteine β C−H bond and the ring closure that occurs during the conversion

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only observed if the β-H adjacent to the sulfur are deuterated

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Upon acidification releases H₂O₂

Fe/O₂ 2:1 ratio

Formation of peroxo-bridged species

EPR Silent

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UV−vis absorption spectra of 3 and 4 at -40 ^oC

Kovacs et al. J. Am. Chem. Soc. 2022, 144, 8515

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stable for weeks at −80 °C

low-spin Fe(III)

Peroxo-bridged conversion to other Species

Simultaneously monitoring the –40 ˚C conversion of 4 to 6 by X-band EPR and electronic absorption spectroscopy

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5

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Kovacs et al. J. Am. Chem. Soc. 2022, 144, 8515

UV-vis Spectra showing 4 converts to 5 upon warming to 25 ˚C in MeOH

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Proposed mechanism for the formation of hydroxo species

Green Crystal

Rate of conversion of 4 to 6 in CH₃OH and CD₃OD at −40 °C

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6

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k_H/k_D = 4

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Kovacs et al. J. Am. Chem. Soc. 2022, 144, 8515

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Glaser et al. Nat Commun. 2022, 13, 1376

Yellow Crystal

Generation of a [(susan^6-Me){ Fe^III₂(μ-O)(μ-1,2-O₂)}]²⁺

Black Crystal at -30 ^oC

UV−vis spectra in CH₃CN at -10 ^oC

19300 cm⁻¹, μ-oxo→ Fe^III LMCT

15400 cm⁻¹, μ-1,2-peroxo→Fe^III LMCT π*_π→t_2g antiferromagnetic coupling

11800 cm⁻¹

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Generation of a [(susan^6-Me){Fe^IV (μ-O)(μ-1,2-O₂)Fe^III}]³⁺

Glaser et al. Nat Commun. 2022, 13, 1376

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chemical reversibility of the oxidation and indicates the conservation of the μ-oxo,μ-1,2-peroxo motive in the oxidized species

CV of 1 at −20 °C in CH₃CN

The chemically oxidized species (green) almost superimpose with the electrochemically oxidized species (red)

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Characterisation of a [(susan^6-Me){Fe^IV (μ-O)(μ-1,2-O₂)Fe^III}]³⁺

Glaser et al. Nat Commun. 2022, 13, 1376

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UV−vis spectra at -60^oC

Disappreance of 15400 cm⁻¹ μ-1,2-peroxo band

⁵⁷Fe Mössbauer at 180 K

Protonation to [(susan^6-Me){Fe^III(μ-O)(μ-1,2-OOH)Fe^III}]³⁺

Glaser et al. Nat Commun. 2022, 13, 1376

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3

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Glaser et al. Nat Commun. 2022, 13, 1376

Reactivity studies

PPh₃

DHA

TEMPOH

Reactivity 1 at -40 °C in CH₃CN

Reaction of 2 and 3 at -60 °C in CH₃CN/CH₂Cl₂ (1:1)

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Paine et al. Angew. Chem. Int. Ed. 2015, 54, 9338

Dioxygen-derived electrophilic Iron–oxygen oxidant

UV-Vis spectral at 25 °C

Mass spectra of the oxidized solution of 1

33% incorporation of labeled O₂ from H₂O into the ligand

Broad charge transfer at 600 nm

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Reaction of complex-1 with thioanisole

Mass spectra of thioanisole oxide formed in the reaction of 1

no O₂ atom from H₂O is incorporated in the absence of Sc³⁺

Hammett plot obtained from the reaction of 1

confirms the electrophilic nature of the iron–oxygen oxidant generated in the presence of Lewis acid

Paine et al. Angew. Chem. Int. Ed. 2015, 54, 9338

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exchange with H₂O

no exchange with H₂O

Reaction of complex-1 with alkene and alkane

electrophilic oxidant preferentially activates

the tertiary C-H bond

Paine et al. Angew. Chem. Int. Ed. 2015, 54, 9338

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Proposed mechanism for the formation of iron–oxygen oxidants

Paine et al. Angew. Chem. Int. Ed. 2015, 54, 9338

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Structure of nonheme Iron(III)- superoxo complex

Rittle et al. J. Am. Chem. Soc. 2021, 143, 13687

Yellow crystal

red crystal

UV−Vis spectra at −90 °C

stabilizes and harness reactive inorganic species

ν(O−O)∼1130 cm^-1

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Characterisation of Fe(III)- superoxo complex

Rittle et al. J. Am. Chem. Soc. 2021, 143, 13687

⁵⁷Fe Mössbauer spectra at 80 K

X-band EPR spectrum at 5 K

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³¹P{¹H} NMR spectra

Oxidation reaction

Phosphine Oxygen Transfer Reactions

H-Atom Transfer Reactions

Generation of azobenzene

Rittle et al. J. Am. Chem. Soc. 2021, 143, 13687

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k_H/k_D = 4.9

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Nucleophilic aldehyde deformylation

Rittle et al. J. Am. Chem. Soc. 2021, 143, 13687

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Conclusion

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• Naturally occurring enzymes have inspired numerous breakthroughs in the creation of synthetic catalysts for sustainable oxidation processes.

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• It utilizes molecular oxygen for green oxidation chemistry.

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• This platform engages in a range of oxidation reactions that proceed in stoichiometric and catalytic fashion.

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• Species are viable oxidants in both nucleophilic and electrophilic reactions.

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