Abnormal N-heterocyclic Carbene Research Articles

1,3-Imidazole-Based Mesoionic Carbenes and Anionic Dicarbenes: Pushing the Limit of Classical N-Heterocyclic Carbenes.

Classical N-heterocyclic carbenes (NHCs) featuring the carbene center at the C2-position of 1,3-imidazole framework (i.e. C2-carbenes) are well acknowledged as very versatile neutral ligands in molecular as well as in materials sciences. The efficiency and success of NHCs in diverse areas is essentially attributed to their persuasive stereoelectronics, in particular the potent σ-donor property. The NHCs with the carbene center at the unusual C4 (or C5) position, the so-called abnormal NHCs (aNHCs) or mesoionic carbenes (iMICs), are however superior σ-donors than C2-carbenes. Hence, iMICs have substantial potential in sustainable synthesis and catalysis. The main obstacle in this direction is rather demanding synthetic accessibility of iMICs. The aim of this review article is to highlight recent advances, particularly by the author's research group, in accessing stable iMICs, quantifying their properties, and exploring their applications in synthesis and catalysis. In addition, the synthetic viability and use of vicinal C4,C5-anionic dicarbenes (ADCs), also based on an 1,3-imidazole framework, are presented. As will be apparent on following pages, iMICs and ADCs hold potentials in pushing the limit of classical NHCs by enabling access to conceptually new main-group heterocycles, radicals, molecular catalysts, ligands sets, and more.

1,3‐Imidazol‐basierte mesoionische Carbene und anionische Dicarbene: Erweiterung der Grenzen klassischer N‐heterocyclischer Carbene

AbstractKlassische N‐heterocyclische Carbene (NHCs) mit dem Carbenzentrum an der C2‐Position des 1,3‐Imidazolgerüsts (d.h. C2‐Carbene) sind als vielseitige neutrale Liganden sowohl in der Molekularforschung als auch in den Materialwissenschaften bekannt. Die Effizienz und der Erfolg der NHCs in verschiedenen Bereichen ist im Wesentlichen auf ihre überzeugenden stereoelektronischen Eigenschaften zurückzuführen, insbesondere auf die starke σ‐Donoreigenschaft. Die NHCs mit dem Carbenzentrum an der ungewöhnlichen C4‐ (oder C5‐) Position, die sogenannten abnormalen NHCs (aNHCs) oder mesoionischen Carbene (iMICs), sind jedoch deutlich stärkere σ‐Donatoren als C2‐Carbene. Deshalb haben iMICs ein erhebliches Potenzial als Liganden in der nachhaltigen Synthese und Katalyse. Das Haupthindernis auf diesem Weg ist die anspruchsvolle synthetische Zugänglichkeit zu iMICs. Das Ziel dieses Übersichtsartikels ist es, die aktuellen Fortschritte, insbesondere der Forschungsgruppe des Autors, im Hinblick auf den Zugang zu stabilen iMICs, die Quantifizierung ihrer Eigenschaften sowie die Erforschung ihrer Anwendungen in Synthese und Katalyse aufzuzeigen. Darüber hinaus werden die synthetische Eignung und die Verwendung vicinaler C4,C5‐anionische Dicarbene (ADCs), die ebenfalls auf einem 1,3‐Imidazolgerüst basieren, vorgestellt. Wie auf den folgenden Seiten deutlich wird, haben iMICs und ADCs das Potenzial, die Grenzen der klassischen NHCs zu erweitern, indem sie den Zugang zu konzeptionell neuartigen Hauptgruppenelement‐Heterocyclen, Radikalen, molekularen Katalysatoren, Ligandensätzen und mehr ermöglichen.

Thermally stable carbazole tagged Au(i)–mesoionic N-heterocyclic carbene complexes with diverse gold–hydrogen bonds

Carbazole tagged abnormal N-heterocyclic carbene–gold(i) complexes with unique gold hydrogen bonding interactions and thermal properties are reported.

The Core Difference between a Mesoionic and a Normal N-Heterocyclic Carbene.

The properties of the abnormal N-heterocyclic carbene (NHC) 1,4-dimesityl-3-methyl-1,2,3-triazolin-5-ylidene were comprehensively compared to those of the related normal carbene 1,3-dimesitylimidazolin-2-ylidene using a range of steric and electronic probe techniques (% Vbur, steric maps, Tolman electronic parameter, alane, Huynh electronic parameter, selone, and pKa values). The two NHCs were determined to be sterically equivalent (isostructural), while the triazolin-5-ylidene was found to be a stronger σ-electron donor and a much weaker π-electron acceptor. These results were used to demonstrate that the electronic properties of these NHCs could affect the stereochemical outcome of an NHC-catalyzed reaction.

Synthesis, Crystal Structure Determination and Electrochemistry of Homoleptic Pd(0) Complexes Supported by Normal and Abnormal N-Heterocyclic Carbene Ligands

Synthesis, Crystal Structure Determination and Electrochemistry of Homoleptic Pd(0) Complexes Supported by Normal and Abnormal N-Heterocyclic Carbene Ligands

Synthesis and Properties of Pyridine-Fused Triazolylidene-Palladium: Catalyst for Cross-Coupling Using Chloroarenes and Nitroarenes.

The synthesis and catalytic activity of pyridine-fused triazolylidene as a novel abnormal N-heterocyclic carbene (aNHC) ligand is described. The evaluation of physical properties using X-ray crystallographic analysis and infrared spectroscopy revealed that these triazolylidenes have a high electron-donating ability toward the metal center. The application of this triazolylidene to the palladium-catalyzed cross-coupling of chloroarenes and nitroarenes with arylboronic acids showcased its ability to activate C-Cl and C-NO2 bonds.

Reusable Single Homogeneous Ir(III)–NHC Catalysts for Bidirectional Hydrogenation–Dehydrogenation of N-Heteroarenes in Water

Bidirectional hydrogenation–dehydrogenation (BHD) catalysis is of utmost importance in the context of hydrogen storage and reutilization. There are several systems based on carbocycles/hydrogenated carbocycles and N-heterocycles/hydrogenated N-heterocycles available for storing H2 gas via hydrogenation and extracting it via the reverse dehydrogenation. However, single bidirectional catalysts to achieve both the hydrogenation and dehydrogenation reactions are rare, especially in water as the desired reaction solvent, and therefore developing such catalysts would lead to a significant development in the area. Moreover, the reuse of homogeneous aqueous-phase BHD catalysts in additional catalytic runs would practicalize a sustainable catalyst-utilization protocol. This work reports such a development where a water-soluble homogeneous iridium catalyst efficiently performed bidirectional hydrogenation–dehydrogenation of quinoxaline- and quinoline-based heterocycles in H2O under relatively mild conditions (1 atm H2, 50 °C for hydrogenation, and 100 °C for dehydrogenation), and it could be reused for running additional reaction cycles, thereby improving the net efficiency. Further, the catalyst was found to be durable as a 40 day-old stock solution of the catalyst in water still maintained high activity. A unique ligand platform consisting of uracil-containing abnormal N-heterocyclic carbene (aNHC) around the Cp*Ir center in the catalyst enabled the desired properties such as water-solubility (required for catalyst separation/reuse), metal–ligand bifunctional activation of H2 and hydrogenated N-heterocycles (during hydrogenation/dehydrogenation), and efficient hydride delivery (during hydrogenation/dehydrogenation). The mechanistic steps, as analyzed by computational studies, underscored that the activation and release of H2 were the rate-determining steps in the hydrogenation and dehydrogenation, respectively.

Regioselective ring-opening of epoxides towards Markovnikov alcohols: a metal-free catalytic approach using abnormal N-heterocyclic carbene.

Herein we report the first metal-free regioselective Markovnikov ring-opening of epoxides (selectivity up to 99%) using an abnormal N-heterocyclic carbene (aNHC) to yield secondary alcohols. DFT calculations and X-ray crystallography suggest that the Markovnikov selectivity originates from the high nucleophilicity and steric factors associated with the aNHC.

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.

Nickel(II) complexes containing tridentate ONCi ligands (i = abnormal N-heterocyclic carbene donors) and their catalytic application in Suzuki-Miyaura coupling reaction.

New nickel complexes with tridentate phenoxy-amidate-aNHC donor groups were synthesized from the reactions between nickel acetate and imidazolium ligand precursors in net pyridine. An unusual degradation pathway was observed, leading to imidazole derivatives occupying the fourth coordination sites in these square planar complexes. A new imidazole-coordinated nickel complex was found to be efficient in catalyzing Suzuki-Miyaura cross-coupling with aryl chlorides under 3 mol% of catalyst loading. The catalytic activities were superior to those of its reported normal NHC counterpart. Instead of the common procedure of using additional phosphine, the addition of IMes·HCl significantly enhances the product yields of the catalytic reaction.

Cationic Charge-Appended Abnormal Carbenes: Synthesis and Study of Electronically Modified Abnormal N-Heterocyclic Carbenes.

A range of palladium complexes featuring electronically modified, imidazole-based abnormal N-heterocyclic carbene (aNHC) ligands have been prepared in the hopes of accessing a new class of cationic aNHC ligands electronically distinct from normal NHCs and aNHCs. These palladium complexes represent the first examples of transition metal-ligated aNHC complexes featuring a cationic moiety adjacent to the abnormal carbene center. It was anticipated that these design principles could facilitate electron transfer between the imidazolinylidene and the cationic heterocycle, thus reducing the electron density at the abnormal carbene center. However, this case study suggests that greater conformational restrictions that allow for heterocycle coplanarity are necessary to achieve significant electron transfer and enable access to a new class of cationic charge-appended aNHCs with unique electronic properties.

Ruthenium(II) complexes bearing chelating Carboxylate-anchored normal and abnormal Carbenes: Synthesis, characterizations and catalytic applications

Functionalized abnormal/mesoionic NHC (NHC = N-heterocyclic carbene) complexes have been much less investigated in contrast to their normal NHC counterparts. In this work, a series of [Ccarbene^Ocarboxylate]- and [Ccarbene^C’phenyl]-type Ru(II) complexes bearing normal and abnormal NHCs have been synthesized. Their spectroscopic features, solid-state structure and aquation reactivity have also been reported. All the as-synthesized complexes have served as precatalysts to catalyze intramolecular or intermolecular carboxylic acid-to-alkyne addition reactions. It was found that the catalytic behavior of abnormal NHC complexes is superior to that of the normal NHC analogs. An anti-Markovnikov addition reactivity, leading to the formation of an E-type enol ester as the major product, was observed. A few stoichiometric experiments have also been carried out to provide preliminary insight into the catalytic mechanism.

Progressing the Frustrated Lewis Pair Abilities of N-Heterocyclic Carbene/GaR3 Combinations for Catalytic Hydroboration of Aldehydes and Ketones.

Exploiting the steric incompatibility of the tris(alkyl)gallium GaR3 (R = CH2SiMe3) and the bulky N-heterocyclic carbene (NHC) 1,3-bis(tert-butyl)imidazol-2-ylidene (ItBu), here we report the B-H bond activation of pinacolborane (HBPin), which has led to the isolation and structural authentication of a novel ion pair, [{ItBu-BPin}+{GaR3(μ-H)GaR3}-] (2). Contrastingly, neither ItBu or GaR3 was able to react with HBPin under the conditions of this study. Combining an NHC-stabilized borenium cation, [{ItBu-BPin}+], with an anionic dinuclear gallate, [{GaR3(μ-H)GaR3}-], 2 proved to be unstable in solution at room temperature, evolving to the abnormal NHC-Ga complex [BPinC{{N(tBu)]2CHCGa(R)3}] (3). Interestingly, the structural isomer of 2, with the borenium cation residing at the C4 position of the carbene, [{aItBu-BPin}+{GaR3(μ-H)GaR3}-] (4), was obtained when the abnormal NHC complex [aItBu·GaR3] (1) was heated to 70 °C with HBPin, demonstrating that, under these forced conditions, it is possible to induce thermal frustration of the Lewis base/Lewis acid components of 1, enabling the activation of HBPin. Building on these stoichiometric studies, the frustrated Lewis pair (FLP) reactivity observed for the GaR3/ItBu combination with HBPin could then be upgraded to catalytic regimes, allowing the efficient hydroboration of a range of aldehydes and ketones under mild reaction conditions. Mechanistic insights into the possible reaction pathway involved in this process have been gained by combining kinetic investigations with a comparative study of the catalytic capabilities of several gallium and borenium species related to 2. Disclosing a new cooperative partnership, reactions are proposed to occur via the formation of a highly reactive monomeric hydride gallate, [{ItBu-BPin}+{GaR3(H)}-] (I). Each anionic and cationic component of I plays a key role for success of the hydroboration, with the nucleophilic monomeric gallate anion favoring the transfer of its hydride to the C═O bond of the organic substate, which in turn is activated by coordination to the borenium cation.

Si(II) Cation-Promoted Formation of an Abnormal NHC-Bound Silylene and a cAAC-Silanyl Radical Ion.

The reaction of amidinatosilylene LSi(:)Cl [L = PhC(NtBu)2] with N-heterocyclic carbene IAr [:C{N(Ar)CH}2, where Ar = 2,6-iPr2C6H3] and NaOTf in tetrahydrofuran (THF) facilely afforded a silicon(II) cation [LSi(:)-aIAr]+OTf- (1+OTf-), where IAr isomerizes to abnormal N-heterocyclic carbene aIAr, coordinating to the silicon(II) center. Its Ge homologue, [LGe(:)-aIAr]+OTf- (2+OTf-), was also accessed via the same protocol. For the formation of 1+, we propose that an in situ-generated Si(II) cation [LSi(:)]+ under the treatment of LSi(:)Cl with NaOTf may isomerize IAr in THF. In contrast, the replacement of IAr with cyclic alkyl(amino) carbene (cAAC) furnished a cAAC-silanyl radical ion [LSi(H)-cAAC]•+(LiOTf2)- [3•+(LiOTf2)-], which may undergo an abstraction of the H radical from THF. All of the products were characterized by nuclear magnetic resonance spectroscopy, electron paramagnetic resonance, and X-ray crystallography, and their bonding scenarios were investigated by density functional theory calculations. These studies provide new perspective on carbene-silicon chemistry.

Chiral-at-Ruthenium Catalysts with Mixed Normal and Abnormal N-Heterocyclic Carbene Ligands

We recently reported a new class of chiral ruthenium catalysts in which two achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbene ligands in addition to two labile acetonitriles are coordinated to a central ruthenium and generate a stereogenic metal center which is responsible for the overall chirality (Zheng et al. J. Am. Chem. Soc. 2017, 139, 4322). Here we now report our discovery of related chiral-at-ruthenium catalysts in which normal and abnormal N-heterocyclic carbene (NHC) ligands are present at the same time. The synthesis of racemic complexes, their resolution into individual enantiomers by a chiral auxiliary approach, and a catalytic application are reported. The mixed normal/abnormal NHC complexes display significantly increased turnover numbers and turnover frequencies for a nitrene-mediated enantioselective C(sp3)–H amination.

Highly Efficient Ethenolysis and Propenolysis of Methyl Oleate Catalyzed by Abnormal N-Heterocyclic Carbene Ruthenium Complexes in Combination with a Phosphine–Copper Cocatalyst

Fluorinated imidazo[1,5-a]pyridine abnormal carbene ruthenium complexes (F-aImPy–Ru) with a tricyclohexylphosphine copper chloride (Cy3P–CuCl) cocatalyst were developed for the ethenolysis/propenolysis of methyl oleate. These catalysts showed remarkable catalytic efficiencies (turnover numbers of 100,000 for ethenolysis and 200,000 for propenolysis) and excellent α-olefin selectivity (up to 99%). A computational study indicated that the energy barrier of the β-hydride elimination pathway in the presence of a phosphine–copper cocatalyst is higher than that in the absence of the cocatalyst, which might contribute to the improved longevity of the ruthenium catalyst in the reaction.

Abnormal N-Heterocyclic Carbene–Palladium Complexes for the Copolymerization of Ethylene and Polar Monomers

Palladium complexes bearing abnormal imidazo[1,5-a]pyridine (aImPy)-based N-heterocyclic carbene ligands were developed for the homopolymerization of olefins and the copolymerization of olefins and...

Transition metal-free catalytic reduction of primary amides using an abnormal NHC based potassium complex: integrating nucleophilicity with Lewis acidic activation.

An abnormal N-heterocyclic carbene (aNHC) based potassium complex was used as a transition metal-free catalyst for reduction of primary amides to corresponding primary amines under ambient conditions. Only 2 mol% loading of the catalyst exhibits a broad substrate scope including aromatic, aliphatic and heterocyclic primary amides with excellent functional group tolerance. This method was applicable for reduction of chiral amides and utilized for the synthesis of pharmaceutically valuable precursors on a gram scale. During mechanistic investigation, several intermediates were isolated and characterized through spectroscopic techniques and one of the catalytic intermediates was characterized through single-crystal XRD. A well-defined catalyst and isolable intermediate along with several stoichiometric experiments, in situ NMR experiments and the DFT study helped us to sketch the mechanistic pathway for this reduction process unravelling the dual role of the catalyst involving nucleophilic activation by aNHC along with Lewis acidic activation by K ions.

Stable abnormal N-heterocyclic carbenes and their applications.

Although N-heterocyclic carbenes (NHCs) have been known as ligands for organometallic complexes since the 1960s, these carbenes did not attract considerable attention until Arduengo et al. reported the isolation of a metal-free imidazol-2-ylidene in 1991. In 2001 Crabtree et al. reported a few complexes featuring an NHC isomer, namely an imidazol-5-ylidene, also termed abnormal NHC (aNHCs). In 2009, it was shown that providing to protect the C-2 position of an imidazolium salt, the deprotonation occurred at the C-5 position, affording imidazol-5-ylidenes that could be isolated. Over the last ten years, stable aNHCs have been used for designing a range of catalysts employing Pd(ii), Cu(i), Ni(ii), Fe(0), Zn(ii), Ag(i), and Au(i/iii) metal based precursors. These catalysts were utilized for different organic transformations such as the Suzuki-Miyaura cross-coupling reaction, C-H bond activation, dehydrogenative coupling, Huisgen 1,3-dipolar cycloaddition (click reaction), hydroheteroarylation, hydrosilylation reaction and migratory insertion of carbenes. Main-group metal complexes were also synthesized, including K(i), Al(iii), Zn(ii), Sn(ii), Ge(ii), and Si(ii/iv). Among them, K(i), Al(iii), and Zn(ii) complexes were used for the polymerization of caprolactone and rac-lactide at room temperature. In addition, based on the superior nucleophilicity of aNHCs, relative to that of their nNHCs isomers, they were used for small molecules activation, such as carbon dioxide (CO2), nitrous oxide (N2O), tetrahydrofuran (THF), tetrahydrothiophene and 9-borabicyclo[3.3.1]nonane (9BBN). aNHCs have also been shown to be efficient metal-free catalysts for ring opening polymerization of different cyclic esters at room temperature; they are among the most active metal-free catalysts for ε-caprolactone polymerization. Recently, aNHCs successfully accomplished the metal-free catalytic formylation of amides using CO2 and the catalytic reduction of carbon dioxide, including atmospheric CO2, into methanol, under ambient conditions. Although other transition metal complexes featuring aNHCs as ligand have been prepared and used in catalysis, this review article summarize the results obtained with the isolated aNHCs.

Nickel-Catalyzed C(sp2)–H Borylation of Arenes

In this study, C(sp2)–H borylation of arenes was accomplished by a nickel catalyst, resulting in good yield. Alkyl and alkoxy arenes were successfully functionalized, affording C(sp2)–H borylated compounds. It was unraveled that the well-defined abnormal N-heterocyclic carbene based Ni(II) complex breaks into Ni nanoparticles (Ni-NPs), which act as catalytically active species. A series of controlled reactions under stoichiometric conditions along with spectroscopic studies and single-crystal X-ray crystallographic study helped us to understand the formation of Ni-NPs along with formation of a boron(III) compound during this reaction.