Iron Carbene Research Articles

Cyclopropanation with Non-Stabilized Carbenes via Ketyl Radicals.

A radical mechanism enables simple and robust access to nonstabilized, alkyl iron carbenes for novel (2 + 1) cycloadditions. This Fe-catalyzed strategy employs simple, aliphatic aldehydes as carbene precursors in a practical, efficient, and stereoselective cyclopropanation. This air- and water-tolerant method permits convenient generation of iron carbenes and coupling to an exceptionally wide range of sterically and electronically diverse alkenes (nucleophilic, electrophilic, and neutral). A transient ketyl radical intermediate is key to accessing and harnessing this rare, alkyl iron carbene reactivity. Mechanistic experiments confirm the (a) intermediacy of ketyl radicals, (b) iron carbene formation by radical capture, and (c) nonconcerted nature of the (2 + 1) cycloaddition.

Redox Engineering of Myoglobin by Cofactor Substitution to Enhance Cyclopropanation Reactivity

AbstractDesign of metal cofactor ligands is essential for controlling the reactivity of metalloenzymes. We investigated a carbene transfer reaction catalyzed by myoglobins containing iron porphyrin cofactors with one and two trifluoromethyl groups at peripheral sites (FePorCF3 and FePor(CF3)2, respectively), native heme and iron porphycene (FePc). These four myoglobins show a wide range of Fe(II)/Fe(III) redox potentials in the protein of +147 mV, +87 mV, +42 mV and −198 mV vs. NHE, respectively. Myoglobin reconstituted with FePor(CF3)2 has a more positive potential, which enhances the reactivity of a carbene intermediate with alkenes, and demonstrates superior cyclopropanation of inert alkenes, such as aliphatic and internal alkenes. In contrast, engineered myoglobin reconstituted with FePc has a more negative redox potential, which accelerates the formation of the intermediate, but has low reactivity for inert alkenes. Mechanistic studies indicate that myoglobin with FePor(CF3)2 generates an undetectable active intermediate with a radical character. In contrast, this reaction catalyzed by myoglobin with FePc includes a detectable iron–carbene species with electrophilic character. This finding highlights the importance of redox‐focused design of the iron porphyrinoid cofactor in hemoproteins to tune the reactivity of the carbene transfer reaction.

Using Iron L-Edge and Nitrogen K-Edge X-ray Absorption Spectroscopy to Improve the Understanding of the Electronic Structure of Iron Carbene Complexes.

Iron-centered N-heterocyclic carbene compounds have attracted much attention in recent years due to their long-lived excited states with charge transfer (CT) character. Understanding the orbital interactions between the metal and ligand orbitals is of great importance for the rational tuning of the transition metal compound properties, e.g., for future photovoltaic and photocatalytic applications. Here, we investigate a series of iron-centered N-heterocyclic carbene complexes with +2, + 3, and +4 oxidation states of the central iron ion using iron L-edge and nitrogen K-edge X-ray absorption spectroscopy (XAS). The experimental Fe L-edge XAS data were simulated and interpreted through restricted-active space (RAS) and multiplet calculations. The experimental N K-edge XAS is simulated and compared with time-dependent density functional theory (TDDFT) calculations. Through the combination of the complementary Fe L-edge and N K-edge XAS, direct probing of the complex interplay of the metal and ligand character orbitals was possible. The σ-donating and π-accepting capabilities of different ligands are compared, evaluated, and discussed. The results show how X-ray spectroscopy, together with advanced modeling, can be a powerful tool for understanding the complex interplay of metal and ligand.

Iron Olefin Metathesis: Unlocking Reactivity and Mechanistic Insights.

Olefin metathesis catalyzed by iron complexes has garnered substantial interest due to iron's abundance and nontoxicity relative to ruthenium, yet its full potential remains untapped, largely because of the propensity of iron carbenes to undergo cyclopropanation instead of cycloreversion from a metallacycle intermediate. In this report, we elucidate the reactions of [{PC(sp2)P}Fe(L)(N2)], ([PC(sp2)P] = bis[2-(diisopropylphosphino)phenyl]methylene) with strained olefins, unveiling their capability to yield metathesis-related products. Our investigations led to the isolation of a structurally characterized metallacyclobutane during the reaction with norbornadiene derivatives, ultimately leading to a ring-opened iron alkylidene. These findings provide compelling evidence that iron complexes adhere to the Chauvin olefin metathesis mechanism.

Unlocking carbene reactivity by metallaphotoredox α-elimination.

The ability to tame high-energy intermediates is important for synthetic chemistry, enabling the construction of complex molecules and propelling advances in the field of synthesis. Along these lines, carbenes and carbenoid intermediates are particularly attractive, but often unknown, high-energy intermediates1,2. Classical methods to access metal carbene intermediates exploit two-electron chemistry to form the carbon-metal bond. However, these methods are usually prohibitive because of reagent safety concerns, limiting their broad implementation in synthesis3-6. Mechanistically, an alternative approach to carbene intermediates that could circumvent these pitfalls would involve two single-electron steps: radical addition to metal to forge the initial carbon-metal bond followed by redox-promoted α-elimination to yield the desired metal carbene intermediate. Here we realize this strategy through a metallaphotoredox platform that exploits iron carbene reactivity using readily available chemical feedstocks as radical sources and α-elimination from six classes of previously underexploited leaving groups. These discoveries permit cyclopropanation and σ-bond insertion into N-H, S-H and P-H bonds from abundant and bench-stable carboxylic acids, amino acids and alcohols, thereby providing a general solution to the challenge of carbene-mediated chemical diversification.

Hollow Microporous Organic Polymer@Hypercrosslinked Polymer Catalysts Bearing N-Heterocyclic Carbene–Iron Species for the Synthesis of Biomass-Derived Polymer Platforms

Hollow Microporous Organic Polymer@Hypercrosslinked Polymer Catalysts Bearing <i>N</i>-Heterocyclic Carbene–Iron Species for the Synthesis of Biomass-Derived Polymer Platforms

Synthesis and crystal structure of an iron triazole complex resulting from the unexpected ligand cleavage of a triazolium carbene precursor.

Typically reactions of N-heterocyclic carbenes with transition metals are straightforward and require a carbene salt, a base strong enough to deprotonate such a salt and a metal. Yet when carbene precursors are in the form of triazolium salts, reaction may not proceed as easily as expected. In our work, we intended to obtain a triazolylidene complex of iron(II) chloride, but due to the presence of small amounts of water in the tetrahydrofuran solvent used, bis(acetonitrile)tetrakis(1-benzyl-1H-1,2,4-triazole-κN4)iron(II) μ-oxido-bis[trichloridoferrate(III)] acetonitrile disolvate, [Fe(C9H9N3)4(CH3CN)2][Fe2Cl6O]·2CH3CN - an interesting anion with a linear geometry of the O atom - was formed instead of the iron carbene complex. Reaction proceeded via cleavage of the alkyl N-substituent of the triazolium salt. The formation of the product was confirmed by X-ray crystallography. The crystal structure and possible reaction pathways are discussed.

Iron(III) Carbene Complexes with Tunable Excited State Energies for Photoredox and Upconversion.

Substituting precious elements in luminophores and photocatalysts by abundant first-row transition metals remains a significant challenge, and iron continues to be particularly attractive owing to its high natural abundance and low cost. Most iron complexes known to date face severe limitations due to undesirably efficient deactivation of luminescent and photoredox-active excited states. Two new iron(III) complexes with structurally simple chelate ligands enable straightforward tuning of ground and excited state properties, contrasting recent examples, in which chemical modification had a minor impact. Crude samples feature two luminescence bands strongly reminiscent of a recent iron(III) complex, in which this observation was attributed to dual luminescence, but in our case, there is clear-cut evidence that the higher-energy luminescence stems from an impurity and only the red photoluminescence from a doublet ligand-to-metal charge transfer (2LMCT) excited state is genuine. Photoinduced oxidative and reductive electron transfer reactions with methyl viologen and 10-methylphenothiazine occur with nearly diffusion-limited kinetics. Photocatalytic reactions not previously reported for this compound class, in particular the C-H arylation of diazonium salts and the aerobic hydroxylation of boronic acids, were achieved with low-energy red light excitation. Doublet-triplet energy transfer (DTET) from the luminescent 2LMCT state to an anthracene annihilator permits the proof of principle for triplet-triplet annihilation upconversion based on a molecular iron photosensitizer. These findings are relevant for the development of iron complexes featuring photophysical and photochemical properties competitive with noble-metal-based compounds.

Cyclopropanes from iron carbenes

Cyclopropanes from iron carbenes

Cyclopropanation of unactivated alkenes with non-stabilized iron carbenes

Cyclopropanes are ubiquitous in medicines, yet robust synthetic access to a wide range of sterically and electronically diverse analogs remains a challenge. To address the synthetic limitations of the most direct strategy, (2+1) cycloaddition, we sought to develop a variant that employs non-stabilized carbenes. We present herein an FeCl2-catalyzed cyclopropanation that uniquely employs aliphatic (enolizable) aldehydes as carbene precursors. A remarkably broad range of alkenes may be coupled with these non-stabilized, alkyl carbenes. This extensive scope enables the synthesis of novel classes of cyclopropanes bearing alkyl, benzyl, allyl, halide, and heteroatom substituents, as well as spirocyclic and fused bicycles. Over 40 examples illustrate the broad generality, efficiency, selectivity, functional group tolerance, and practical utility of this approach. Mechanistic insights, gathered from stereochemical probes and competition experiments, are included to reveal the applicability of this non-stabilized carbene route for novel cyclopropane synthesis.

Iron Heme Enzyme-Catalyzed Cyclopropanations with Diazirines as Carbene Precursors: Computational Explorations of Diazirine Activation and Cyclopropanation Mechanism.

The mechanism of cyclopropanations with diazirines as air-stable and user-friendly alternatives to commonly employed diazo compounds within iron heme enzyme-catalyzed carbene transfer reactions has been studied by means of density functional theory (DFT) calculations of model systems, quantum mechanics/molecular mechanics (QM/MM) calculations, and molecular dynamics (MD) simulations of the iron carbene and the cyclopropanation transition state in the enzyme active site. The reaction is initiated by a direct diazirine-diazo isomerization occurring in the active site of the enzyme. In contrast, an isomerization mechanism proceeding via the formation of a free carbene intermediate in lieu of a direct, one-step isomerization process was observed for model systems. Subsequent reaction with benzyl acrylate takes place through stepwise C-C bond formation via a diradical intermediate, delivering the cyclopropane product. The origin of the observed diastereo- and enantioselectivity in the enzyme was investigated through MD simulations, which indicate a preferred formation of the cis-cyclopropane by steric control.

Directed C–H activation with iron carbene complexes

The reactivity of PCcarbeneP iron carbenes, was investigated toward imines, ketones, diazenes, 2-vinylpyridine, and 8-methylquinoline, revealing the directed activation of aryl, vinyl, or benzyl C–H bonds by 1,2-addition across the iron-carbene bond.

Stereogenic-at-iron mesoionic carbene complex for enantioselective C-H amidation.

Electronically tuned C 2-symmetric stereogenic-at-iron complexes, featuring strongly σ-donating 1,2,3-triazolin-5-ylidene mesoionic carbene (MIC) ligands, exhibit enhanced catalytic efficiency compared to conventional imidazol-2-ylidene analogs, as demonstrated in nitrene-mediated ring-closing C(sp3)-H amidation reactions. Furthermore, a chiral pinene-derived pyridyl triazole ligand enables a highly diastereoselective synthesis of a non-racemic chiral iron catalyst, thereby controlling the absolute configuration at the metal center, as confirmed by NMR and X-ray crystallography. This pinene-modified stereogenic-at-iron MIC complex demonstrates high catalytic activity and a respectable asymmetric induction in the ring-closing C(sp3)-H amination of N-benzoyloxyurea, yielding 2-imidazolidinones with enantiomeric ratios of up to 92 : 8. These findings reflect the profound potential of this new class of mesoionic carbene iron complexes in further understanding and tuning the reactivity of iron-based catalysts.

Mechanistic and chemoselective investigations on nitrene transfer reactions mediated by a novel iron-mesoionic carbene catalyst

The mesoionic carbene iron complex is a new catalyst, and its catalytic mechanisms for the nitrene transfer reactions were investigated via density functional theory calculations. Especially, the amination-to-aziridination chemoselectivity is predicted for the first time. The origin of the chemoselectivity toward C(sp3)–H amination has been revealed. Based on our calculated results, it can be suggested that the substrate scope of this novel catalytic system may be expanded to alkenes to greatly broaden its potential applications in constructing N-heterocyclic compounds.

Computational Study of Iron-Catalyzed Intramolecular [2 + 2] Cycloaddition and Cycloisomerization of Enyne Acetates: Mechanism and Selectivity

The mechanism of iron-catalyzed intramolecular [2 + 2] cycloaddition and cycloisomerization of enyne acetates has been investigated with DFT computations. Both mechanisms start the catalytic cycle from the stepwise 1,2-acyloxy migration to afford the iron carbene. The [2 + 2] cycloaddition mechanism involves subsequent key steps of [2 + 2] cycloaddition, 1,2-acyloxy migration, and reductive elimination to generate the azabicyclo [3.2.0] heptane product, with the reductive elimination being the rate-determining step. The cycloisomerization mechanism involves subsequent key steps of [2 + 2] cycloaddition, stepwise 1,4-acyloxy migration to produce the allenylpyrrolidine product, with the 1,4-acyloxy migration being the rate-determining step. Reaction potential energy surfaces for two model substrates that have or do not have alkene-terminal substituents have been investigated and the origins of the selectivities have been disclosed. Moreover, energy profiles with three possible spin states (SFe = 0, 1, 2) have been considered. The reaction is suggested to occur mainly on the singlet potential energy surface with a few spin crossovers between singlet and triplet states involved, which indicates that this reaction should have two-state reactivity (TSR).

Carbene-Like Reactivity in an Iron Azametallacyclobutene Complex: Insights from Electronic Structure.

Herein we describe our investigation into the electronic structure of the first isolated monometallic iron azametallacyclobutene complex. Computational analysis through density functional theory calculations reveals electron delocalization throughout the four atoms of the ring system, in line with experimental observations and supporting the classification of this complex as a conjugated metallacycle. The results of this study also point to significant contribution from an imine-substituted iron carbene resonance structure to the overall bonding picture for the azametallacyclobutene. Accordingly, this complex participates in carbene-like reactivity in the presence of an isocyanide substrate to generate a ketenimine product. The related reaction with carbon monoxide leads to the isolation of a five-membered metallacycle that is analogous to the proposed intermediate in ketenimine formation, and confirms the α-carbon as the site of reactivity.

Electrochemical polymerisation of newly synthesised 3,4-ethylene dioxythiophene-N-heterocyclic carbene iron complexes and application as redox mediators

Immobilization of redox active complexes as electrodes modifier is appealing for a large set of applications such as sensing, electrolysers or fuel cell. In this work iron based N-heterocyclic carbene complexes bearing an 3,4‑Ethylene dioxythiophene (EDOT) moiety in the side chain have been prepared following two different synthetic approaches determined by the length of the lateral chain. The approaches exploit carbonyldiimidazole (CDI) as the coupling agent between the –CH2OH moiety of the hydroxymethyl-EDOT and the –OH functionalized N-heterocyclic carbene iron complex or the imidazolium salt precursor. In both cases, the syntheses allow to obtain functional monomers suitable for electrochemical polymerization in the form of thin films on conducting substrates. The modified electrodes have been characterized by ATR-IR, showing successful copolymerisation to functionalized poly(3,4‑ethylene dioxythiophene) (PEDOT), by cyclic voltammetry (CV), demonstrating the dominant and reversible redox response of NHC-iron complexes, and by SEM-EDS, which provides the average copolymerisation ratio. The capability of the NHC-iron complex to act as a redox mediator has been assessed by using the functionalized device for glucose detection.

Carbene Transfer from a Pyridine Dipyrrolide Iron–Carbene Complex: Reversible Migration of a Diphenylcarbene Ligand into an Iron–Nitrogen Bond

Carbene Transfer from a Pyridine Dipyrrolide Iron–Carbene Complex: Reversible Migration of a Diphenylcarbene Ligand into an Iron–Nitrogen Bond

Iron-N-heterocyclic carbene complexes as efficient electrocatalysts for water oxidation under acidic conditions.

The development of stable, Earth-abundant, and high-activity molecular water oxidation catalysts under acidic and neutral conditions remains a great challenge. Here, the use of N-heterocyclic carbene (NHC)-based iron(III) complex 1 {[phenyl(tris(3-methylimidazol-1-ylidene))borate]2Fe(III)}+ as a catalyst for water oxidation under acidic and neutral conditions was investigated. Two iron(II) carbene complexes, 2 {[2,6-bis(3-methylimidazolium-1-yl)pyridine]2Fe}2+ and 3 {[2,6-bis(3-methylimidazolium-1-yl)pyridine-4-carboxylic acid]2Fe}2+, were also used for comparison. A series of experiments demonstrate that complex 1 has excellent performance in terms of both catalytic activity and stability. In addition, the faradaic efficiency and turnover frequency (TOF) reach 95.0% and 2.8 s-1, respectively. An overpotential of ca. 490 mV is obtained at pH 1.5. Density functional theory (DFT) calculations indicate that dehydrogenation is the potential-determining step (PDS) in water oxidation. Complex 1 has a lower free energy barrier in this process than 2 and 3. High-valent Fe species are further proven in 1 by spectroelectrochemical measurements, which are crucial in promoting water oxidation. This study is expected to contribute to the development of homogeneous water oxidation catalysis under acidic and neutral conditions.

The first macrocyclic abnormally coordinating tetra-1,2,3-triazole-5-ylidene iron complex: a promising candidate for olefin epoxidation.

The first macrocyclic and abnormally coordinating, mesoionic N-heterocyclic carbene iron complex has been synthesised and characterised via ESI-MS, EA, SC-XRD, CV, NMR and UV/Vis spectroscopy. 13C-NMR spectroscopy and CV measurements indicate a strong σ-donor ability of the carbene moieties, suggesting an efficient catalytic activity of the iron complex in oxidation reactions. Initial tests in the epoxidation of cis-cyclooctene as a model substrate confirm this assumption.