Iron Carbene Research Articles

N-Heterocyclic carbene iron complexes catalyze the ring-opening polymerization of lactide.

Poly(lactic acid), PLA, which holds great promise as a biodegradable substitute of fossil resource-derived polyolefins, is industrially produced by the ring-opening polymerization of lactide using a potentially harmful tin catalyst. Based on mechanistic insights into the reaction of N-heterocyclic carbene (NHC) iron complexes with carbonyl substrates, we surmised and demonstrate here that such complexes are excellent catalysts for the bulk polymerization of lactide. We show that an iron complex with a triazolylidene NHC ligand is active at lactide/catalyst ratios of up to 10 000 : 1, produces polylactide with relatively high number-average molecular weights (up to 50 kg mol−1) and relatively narrow dispersity (Đ ∼ 1.6), and features an apparent polymerization rate constant kapp of up to 8.5 × 10−3 s−1, which is more than an order of magnitude higher than that of the industrially used tin catalyst. Kinetic studies and end-group analyses support that the catalytically active species is well defined and that the polymerization proceeds via a coordination–insertion mechanism. The robustness of the catalyst allows technical grade lactide to be polymerized, thus offering ample potential for application on larger scale in an industrially relevant setting.

Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes

Two photoactive iron N-heterocyclic carbene complexes {[hbox {Fe}^{{{rm{II}}}}(hbox {btz})_2(hbox {bpy})]^{2+}} and {[hbox {Fe}^{{rm{III}}}(hbox {btz})_3]^{3+}}, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic structure properties and ligand-field interactions, as well as information about the resonantly photo-oxidised final states. Comparing measurements of the Fe centre and the surrounding ligands demonstrate strong mixing of the Fe {hbox {t}_{{rm{2g}}}} levels with occupied ligand pi orbitals but weak mixing with the corresponding unoccupied ligand orbitals. This highlights the importance of pi-accepting and -donating considerations in ligand design strategies for photofunctional iron carbene complexes. Spin-propensity is also observed as a final-state effect in the RPES measurements of the open-shell hbox {Fe}^{{rm{III}}} complex. Vibronic coupling is evident in both complexes, where the energy dispersion hints at a vibrationally hot final state. The results demonstrate the significant impact of the iron oxidation state on the frontier electronic structure and highlights the differences between the emerging class of hbox {Fe}^{{rm{III}}} photosensitizers from those of more traditional hbox {Fe}^{{rm{II}}} complexes.

Probing Redox Non-Innocence in Iron-Carbene Complexes {Fe=C(H)Ar}10-11 by 1,2 H and 13 C Pulse Electron Paramagnetic Resonance.

We report the synthesis and spectroscopic characterization of a series of iron-carbene complexes in redox states {Fe=C(H)Ar}10-11 . Pulse EPR studies of the 1,2 H and 13 C isotopologues of {Fe=C(H)Ar}11 reveal the high covalency of the Fe-carbene bonding, leading to a more even spin distribution than commonly observed for reduced Fischer carbenes.

Probing Redox Non‐Innocence in Iron–Carbene Complexes {Fe=C(H)Ar}10–11by1,2H and13C Pulse Electron Paramagnetic Resonance

AbstractWe report the synthesis and spectroscopic characterization of a series of iron‐carbene complexes in redox states {Fe=C(H)Ar}10–11. Pulse EPR studies of the1,2H and13C isotopologues of {Fe=C(H)Ar}11reveal the high covalency of the Fe–carbene bonding, leading to a more even spin distribution than commonly observed for reduced Fischer carbenes.

N-Heterocyclic Carbene Iron Complexes as Anticancer Agents: In Vitro and In Vivo Biological Studies.

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.

Ethyl cellulose derived porous iron@N-doped carbon material for N–H carbene insertion reaction

A newly developed, facile and sustainable strategy, in which zinc salt, melamine and ethyl cellulose are applied as pore-forming agent, nitrogen and carbon source respectively, has been disclosed for the synthesis of Fe/N-codoped carbon materials. This material exhibits excellent catalytic efficiency towards N–H carbene insertion reaction for the synthesis of unnatural amino acid derivatives. Fe/FeOx nanoparticles tranfer electrons to N-doped carbon owing to the Mott-Schottky Effect, which is beneficial to the formation of iron carbene intermediate. N-doping can offer more Lewis base sites, which promotes the proton transfer process. Fe/FeOx nanoparticles are coated with graphitic carbon, thereby avoiding the loss and deactivation of iron sites in this material. Therefore, this material can be reused at least four times without significant loss in activity.

Requirements for Late-Stage Hydroboration of Pyridine N-Heterocyclic Carbene Iron(0) Complexes: The Role of Ancillary Ligands

Requirements for Late-Stage Hydroboration of Pyridine N-Heterocyclic Carbene Iron(0) Complexes: The Role of Ancillary Ligands

Access to and Reactivity of Fe0, Fe−I, FeI, and FeII PCcarbeneP Pincer Complexes

AbstractDespite their promising metal–ligand cooperative reactivity, PCcarbeneP pincer ligands are rarely reported for first‐row transition‐metal centres. Using a dehydration methodology, we report access to an Fe0 PCcarbeneP pincer complex (1) that proceeds via an isolated α‐hydroxylalkyl hydrido complex (3). Reversible carbonyl migration to the carbene position in 1 is found to allow coordination chemistry and E−H bond addition (E=H, B, Cl) across the iron–carbene linkage, representing a unique mechanism for metal–ligand cooperativity. The PCcarbeneP pincer ligand is also found to stabilize formal FeII, FeI, and Fe−I oxidation states, as demonstrated with synthesis and characterization of the complexes [11‐X][BArF20] (X=Br, I), 12, and K[13]. Compound K[13] is found to be highly reactive, and abstracts hydrogen from a range of aliphatic C−H sources. Computational analysis by DFT suggests that the formal FeI and Fe−I complexes contain significant carbene radical character. The ability of the PCcarbeneP ligand scaffold to partake in metal–ligand cooperativity and to support a range of iron oxidation states renders it as potentially useful in many catalytic applications.

Access to and Reactivity of Fe0 , Fe-I , FeI , and FeII PCcarbene P Pincer Complexes.

Despite their promising metal-ligand cooperative reactivity, PCcarbene P pincer ligands are rarely reported for first-row transition-metal centres. Using a dehydration methodology, we report access to an Fe0 PCcarbene P pincer complex (1) that proceeds via an isolated α-hydroxylalkyl hydrido complex (3). Reversible carbonyl migration to the carbene position in 1 is found to allow coordination chemistry and E-H bond addition (E=H, B, Cl) across the iron-carbene linkage, representing a unique mechanism for metal-ligand cooperativity. The PCcarbene P pincer ligand is also found to stabilize formal FeII , FeI , and Fe-I oxidation states, as demonstrated with synthesis and characterization of the complexes [11-X][BArF 20 ] (X=Br, I), 12, and K[13]. Compound K[13] is found to be highly reactive, and abstracts hydrogen from a range of aliphatic C-H sources. Computational analysis by DFT suggests that the formal FeI and Fe-I complexes contain significant carbene radical character. The ability of the PCcarbene P ligand scaffold to partake in metal-ligand cooperativity and to support a range of iron oxidation states renders it as potentially useful in many catalytic applications.

A Concise Route to Cyclic Amines from Nitroarenes and Ketoacids under Iron‐Catalyzed Hydrosilylation Conditions

AbstractStarting from nitroarenes, under hydrosilylation conditions, using a well‐defined N‐heterocyclic carbene iron(0) catalyst, (IMes)Fe(CO)4, the corresponding aniline derivatives were produced in 61–92% isolated yields. More impressively, a selective synthesis of cyclic amines such as pyrrolidines, piperidines and azepanes were conducted from levulinic acid, 1,5‐ and 1,6‐keto acids, respectively. The sequential procedure proceeded under both visible light irradiation and thermal conditions with 20 examples in isolated yields up to 69%.magnified image

2+2] Cycloadditions with an Iron Carbene: A Critical Step in Enyne Metathesis.

Ruthenium carbenes, famously used in olefin metathesis, have impacted numerous research areas, ranging from synthesis to materials and biology. Although in the same group as ruthenium, iron carbenes showing similar reaction patterns have not been reported. Such targets are of high interest because the use of a sustainable metal would lead to a decreased cost, toxicity, and environmental impact of the corresponding compounds. Herein, we report the synthesis of an iron carbene complex, [{PC(sp2)P}Fe(N2)(PMe3)] ([PC(sp2)P] = (bis[2-(di-isopropylphosphino)phenyl]methylene), which is capable of performing [2+2] cycloaddition reactions in the presence of alkynes. Specifically, η3-vinyl carbenes are formed stoichiometrically through a [2+2] cycloaddition between the alkyne and the metal carbene. Additional reactivity of the η3-vinyl carbenes with alkynes yields a second insertion product containing a new iron carbene moiety.

Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer.

ConspectusDespite the astonishing diversity of naturally occurring biocatalytic processes, enzymes do not catalyze many of the transformations favored by synthetic chemists. Either nature does not care about the specific products, or if she does, she has adopted a different synthetic strategy. In many cases, the appropriate reagents used by synthetic chemists are not readily accessible to biological systems. Here, we discuss our efforts to expand the catalytic repertoire of enzymes to encompass powerful reactions previously known only in small-molecule catalysis: formation and transfer of reactive carbene and nitrene intermediates leading to a broad range of products, including products with bonds not known in biology. In light of the structural similarity of iron carbene (Fe=C(R1)(R2)) and iron nitrene (Fe=NR) to the iron oxo (Fe=O) intermediate involved in cytochrome P450-catalyzed oxidation, we have used synthetic carbene and nitrene precursors that biological systems have not encountered and repurposed P450s to catalyze reactions that are not known in the natural world. The resulting protein catalysts are fully genetically encoded and function in intact microbial cells or cell-free lysates, where their performance can be improved and optimized by directed evolution. By leveraging the catalytic promiscuity of P450 enzymes, we evolved a range of carbene and nitrene transferases exhibiting excellent activity toward these new-to-nature reactions. Since our initial report in 2012, a number of other heme proteins including myoglobins, protoglobins, and cytochromes c have also been found and engineered to promote unnatural carbene and nitrene transfer. Due to the altered active-site environments, these heme proteins often displayed complementary activities and selectivities to P450s.Using wild-type and engineered heme proteins, we and others have described a range of selective carbene transfer reactions, including cyclopropanation, cyclopropenation, Si–H insertion, B–H insertion, and C–H insertion. Similarly, a variety of asymmetric nitrene transfer processes including aziridination, sulfide imidation, C–H amidation, and, most recently, C–H amination have been demonstrated. The scopes of these biocatalytic carbene and nitrene transfer reactions are often complementary to the state-of-the-art processes based on small-molecule transition-metal catalysts, making engineered biocatalysts a valuable addition to the synthetic chemist’s toolbox. Moreover, enabled by the exquisite regio- and stereocontrol imposed by the enzyme catalyst, this biocatalytic platform provides an exciting opportunity to address challenging problems in modern synthetic chemistry and selective catalysis, including ones that have eluded synthetic chemists for decades.

Higher MLCT lifetime of carbene iron(II) complexes by chelate ring expansion.

Combining strong σ-donating N-heterocyclic carbene ligands and π-accepting pyridine ligands with a high octahedricity in rigid iron(ii) complexes increases the 3MLCT lifetime from 0.15 ps in the prototypical [Fe(tpy)2]2+ complex to 9.2 ps in [Fe(dpmi)2]2+12+. The tripodal CNN ligand dpmi (di(pyridine-2-yl)(3-methylimidazol-2-yl)methane) forms six-membered chelate rings with the iron(ii) centre leading to close to 90° bite angles and enhanced iron-ligand orbital overlap.

Iron‐Catalyzed Intermolecular Functionalization of Non‐Activated Aliphatic C−H Bonds via Carbene Transfer

AbstractThe modification of strong Csp3−H bonds via iron carbene intermediates under mild reaction conditions has been an important challenge with attractive prospective in organic synthesis. In this work, we show the efficient combination of an electrophilic iron catalyst with a lithium Lewis acid for the functionalization of strong Csp3−H bonds of cyclic and linear alkanes by the activation of commercially available ethyl diazoacetate (EDA). The reaction proceeds with good yields, under mild reaction conditions (40 °C) and large excess of substrate is not needed. In addition, excellent activity is observed in the cyclopropanation of challenging aliphatic olefins.magnified image

Z-Selective Alkyne Functionalization Catalyzed by a trans-Dihydride N-Heterocyclic Carbene (NHC) Iron Complex.

The Z-selective functionalization of terminal alkynes is a useful transformation in organic chemistry and mainly catalyzed by noble metals. Here, we present the Z-selective hydroboration of terminal alkynes catalyzed by a stable trans-dihydride iron complex [(PCNHCP)Fe(H)2N2)] (2). Overall, the reaction occurs at room temperature and provides near quantitative yields of the Z-vinylboronate ester. Interestingly, the same catalyst could also provide the E-vinylboronate by heating the reaction mixture at slightly elevated temperatures (50 °C). If, however, the reaction is performed in the absence of HBpin, rapid Z-selective alkyne dimerization is observed, which is further discussed in this report.

Facile H/D Exchange at (Hetero)Aromatic Hydrocarbons Catalyzed by a Stable Trans-Dihydride N-Heterocyclic Carbene (NHC) Iron Complex.

Earth-abundant metal pincer complexes have played an important role in homogeneous catalysis during the last ten years. Yet, despite intense research efforts, the synthesis of iron PCcarbeneP pincer complexes has so far remained elusive. Here we report the synthesis of the first PCNHCP functionalized iron complex [(PCNHCP)FeCl2] (1) and the reactivity of the corresponding trans-dihydride iron(II) dinitrogen complex [(PCNHCP)Fe(H)2N2)] (2). Complex 2 is stable under an atmosphere of N2 and is highly active for hydrogen isotope exchange at (hetero)aromatic hydrocarbons under mild conditions (50 °C, N2). With benzene-d6 as the deuterium source, easily reducible functional groups such as esters and amides are well tolerated, contributing to the overall wide substrate scope (e.g., halides, ethers, and amines). DFT studies suggest a complex assisted σ-bond metathesis pathway for C(sp2)–H bond activation, which is further discussed in this study.

Reactions of Transition-Metal Carbyne Cations with Ethylene in the Gas Phase

The reactions of iridium- and osmium-carbyne hydride cations [HIrCH]+ and [HOsCH]+ with ethylene have been studied using mass spectrometry with isotopic-labeling in the gas phase. The carbyne reactivity is compared with that of the rhodium, cobalt, and iron analogues [TMCH2]+ (TM = Fe, Co, and Rh), which were determined to have the carbene structures. Besides the cycloaddition/dehydrogenation reaction in forming the [TMC3H4]+ + H2 (TM = Ir and Os) products, a second reaction pathway producing the [TMC2H2]+ ion and CH4 via triple hydrogen atom transfer reactions to the carbyne carbon is observed to be the major channel. The latter channel is not observed in the rhodium, cobalt, and iron carbene cation reactions. Quantum-chemical calculations indicate that the distinct reactivity is not due to different initial structures of the reactants. Both reaction channels are predicted to be thermodynamically exothermic and kinetically facile for the carbyne cations, and the reactions proceed with the initial formation of a carbene intermediate via hydride-carbyne coupling. The latter channel is also exothermic but kinetically unfavorable for the rhodium, cobalt, and iron carbene cations.

Photophysics and Photochemistry of Iron Carbene Complexes for Solar Energy Conversion and Photocatalysis

Earth-abundant first row transition metal complexes are important for the development of large-scale photocatalytic and solar energy conversion applications. Coordination compounds based on iron are especially interesting, as iron is the most common transition metal element in the Earth’s crust. Unfortunately, iron-polypyridyl and related traditional iron-based complexes generally suffer from poor excited state properties, including short excited-state lifetimes, that make them unsuitable for most light-driven applications. Iron carbene complexes have emerged in the last decade as a new class of coordination compounds with significantly improved photophysical and photochemical properties, that make them attractive candidates for a range of light-driven applications. Specific aspects of the photophysics and photochemistry of these iron carbenes discussed here include long-lived excited state lifetimes of charge transfer excited states, capabilities to act as photosensitizers in solar energy conversion applications like dye-sensitized solar cells, as well as recent demonstrations of promising progress towards driving photoredox and photocatalytic processes. Complementary advances towards photofunctional systems with both Fe(II) complexes featuring metal-to-ligand charge transfer excited states, and Fe(III) complexes displaying ligand-to-metal charge transfer excited states are discussed. Finally, we outline emerging opportunities to utilize the improved photochemical properties of iron carbenes and related complexes for photovoltaic, photoelectrochemical and photocatalytic applications.

C-H Functionalization via Iron-Catalyzed Carbene-Transfer Reactions.

The direct C-H functionalization reaction is one of the most efficient strategies by which to introduce new functional groups into small organic molecules. Over time, iron complexes have emerged as versatile catalysts for carbine-transfer reactions with diazoalkanes under mild and sustainable reaction conditions. In this review, we discuss the advances that have been made using iron catalysts to perform C-H functionalization reactions with diazoalkanes. We give an overview of early examples employing stoichiometric iron carbene complexes and continue with recent advances in the C-H functionalization of C(sp2)-H and C(sp3)-H bonds, concluding with the latest developments in enzymatic C-H functionalization reactions using iron-heme-containing enzymes.

There Is a Future for N-Heterocyclic Carbene Iron(II) Dyes in Dye-Sensitized Solar Cells: Improving Performance through Changes in the Electrolyte.

By systematic tuning of the components of the electrolyte, the performances of dye-sensitized solar cells (DSCs) with an N-heterocyclic carbene iron(II) dye have been significantly improved. The beneficial effects of an increased Li+ ion concentration in the electrolyte lead to photoconversion efficiencies (PCEs) up to 0.66% for fully masked cells (representing 11.8% relative to 100% set for N719) and an external quantum efficiency maximum (EQEmax) up to approximately 25% due to an increased short-circuit current density (JSC). A study of the effects of varying the length of the alkyl chain in 1-alkyl-3-methylimidazolium iodide ionic liquids (ILs) shows that a longer chain results in an increase in JSC with an overall efficiency up to 0.61% (10.9% relative to N719 set at 100%) on going from n-methyl to n-butyl chain, although an n-hexyl chain leads to no further gain in PCE. The results of electrochemical impedance spectroscopy (EIS) support the trends in JSC and open-circuit voltage (VOC) parameters. A change in the counterion from I− to [BF4]− for 1-propyl-3-methylimidazolium iodide ionic liquid leads to DSCs with a remarkably high JSC value for an N-heterocyclic carbene iron(II) dye of 4.90 mA cm−2, but a low VOC of 244 mV. Our investigations have shown that an increased concentration of Li+ in combination with an optimized alkyl chain length in the 1-alkyl-3-methylimidazolium iodide IL in the electrolyte leads to iron(II)-sensitized DSC performances comparable with those of containing some copper(I)-based dyes.