Use Of N-heterocyclic Carbenes Research Articles

Cooperative Use of N-Heterocyclic Carbenes and Thiols on a Silver Surface: A Synergetic Approach to Surface Modification.

Surface modification through the formation of a self-assembled monolayer (SAM) can effectively engineer the physicochemical properties of the surface/material. However, the precise design of multifunctional SAMs at the molecular level is still a major challenge. Here, we jointly use N-heterocyclic carbenes (NHCs) and thiols to form multifunctional hetero-SAM systems that demonstrate excellent chemical stability, electrical conductivity, and, in silico, catalytic activity. This synergistic effect is facilitated by the high surface mobility and electron-rich nature of NHCs, combined with the strong binding strength of thiols. Scanning tunneling microscopy, electrical conductivity, and scanning electron microscope measurements, as well as density functional theory calculations, were employed to explore the synergistic interactions in the supramolecular SAMs. The van der Waals integration of ballbot-type NHCs and thiols enables the SAMs to exhibit both superior surface anticorrosion properties (attributing to the shift in the d-band center) and low surface resistance originating from the band alignment. Moreover, we find that the deposition sequence of flat-lying NHCs and thiols results in SAMs with different configurations, which can further tune the mechanistic pathway in silico in the acetylene hydrogenation process. Our results provide essential molecular insights into the local electronic control of the new SAM/metal interface and the high stability of the emergent multifunctionality (NHC/thiol)-SAMs forming self-assembled lamellae structures in the nanometer regime.

NHC aluminum chemistry on the rise.

This perspective highlights recent developments of the use of N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (cAACs) in alane and aluminum organyl chemistry. Especially in the last few years this flourishing research field led to some remarkable discoveries including various substitution patterns at the central aluminum atom, different oxidation states, neutral and charged compounds with varying coordination numbers and unique reactivities. Thereby NHCs play a vital role in the stabilization of these otherwise highly reactive compounds, which would not be realizable without the use of this intriguing class of ligands. Nevertheless, main group hydrides and especially NHC ligated alanes also tend to undergo NHC decomposition reactions, which are part of ongoing research and provide important information for NHC research in general.

Synthesis of γ-Lactams from Acrylamides by Single-Carbon Atom Doping Annulation.

A protocol for single-carbon atom doping annulation is reported, which enables the conversion of acrylamides into homologated γ-lactams through the cleavage of two σ-bonds and the formation of four new σ-bonds at the single carbon center. The key strategy is the use of N-heterocyclic carbenes as an atomic carbon equivalent by acting as carbon atom donors through the loss of a 1,2-diimine moiety. Experimental and computational studies reveal that the reaction proceeds through a spirocyclic intermediate, followed by the disassembly of the N-heterocyclic carbene skeleton via proton transfer.

Stability of N-Heterocyclic Carbene Monolayers Under Continuous Voltammetric Cycling

N-heterocyclic carbenes (NHCs) are promising monolayer-forming chemistries that can overcome limitations of thiol-based monolayers in terms of stability, surface functionality and reactivity across a variety of transition metal surfaces. Recent publications have reported the ability of NHCs to support biomolecular receptors on gold substrates for sensing applications, and improved tolerance to prolonged biofluid exposure relative to thiol chemistries. However, important questions remain regarding the stability of these monolayers when subjected to voltage perturbations, which is needed for technology application in electrochemical platforms. In response, we investigated the ability of two NHC chemistries, 1,3-diisopropylbenzimidazole and 5-(ethoxycarbonyl)-1,3-diisopropylbenzimidazole, to form monolayers via self-assembly from methanolic solutions of their trifluoromethanesulfonate salts. We compared the electrochemical behavior of the resulting monolayers relative to that of benchmark mercaptohexanol monolayers in phosphate-buffered saline. In this presentation I will discuss the results of this study and how they can affect future use of NHCs in electrochemical biosensors.

On the Role of N-Heterocyclic Carbene Salts in Alkyl Radical Generation from Alkyl Alcohols: A Computational Study.

Formation of carbon-carbon bonds through cross-coupling reactions using readily available substrates, like alcohols, is crucial for modern organic chemistry. Recently, direct alkyl alcohol functionalization has been achieved by the use of N-Heterocyclic Carbene (NHC) salts via in situ formation of an alcohol-NHC adduct and its activation by a photoredox catalyst to generate carbon-centered alkyl radicals. Experimentally, only electron deficient NHC activators work but the reasons of this behavior remain underexplored. Herein, a DFT computational study of the mechanism of alcohol activation using up to seven NHC salts is performed to shed light into the influence of their electronic properties in the alkyl radical formation. This study demonstrates that four reaction steps are involved in the transformation and characterizes how the electronic properties of the NHC salt affect each step. A fine balance of the NHC electron-richness is proved to be determinant for this transformation.

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp3)-C(sp3) Bond Formation.

Herein, we present a comprehensive study on the use of N-heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp3)-C(sp3) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies on the use of an acridinium dye to generate the boron-centered radicals from the corresponding NHC-ligated boranes via single-electron transfer (SET) and deprotonation. These boryl radicals subsequently engage with alkyl halides in an XAT step, delivering the desired nucleophilic alkyl radicals. The present XAT strategy is very mild and accommodates a broad scope of alkyl halides, including medicinally relevant compounds and biologically active molecules. The key role of NHC-ligated boryl radicals in the operative reaction mechanism has been elucidated through a combination of experimental, spectroscopic, and computational studies. This methodology stands as a significant advancement in the chemistry of NHC-ligated boryl radicals, which had long been restricted to radical reductions, enabling C-C bond formation under visible-light photoredox conditions.

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.

Unprecedented Use of NHC Gold (I) Complexes as Catalysts for the Selective Oxidation of Ethane to Acetic Acid.

The highly efficient eco-friendly synthesis of acetic acid (40% yield) directly from ethane is achieved by the unprecedented use of N-heterocyclic carbene (NHC) and N-heterocyclic oxo-carbene (NHOC) gold(I) catalysts in mild conditions. This is a selective and promising protocol to generate directly acetic acid from ethane, in comparison with the two most used methods: (i) the three-step, capital- and energy-intensive process based on the high-temperature conversion of methane to acetic acid; (ii) the current industrial methanol carbonylation processes, based in iridium and expensive rhodium catalysts. Green metrics determinations highlight the environmental advantages of the new ethane oxidation procedure. Comparison with previous reported published catalysts is performed to highlight the features of this remarkable protocol.

Electrochemical Generation of N‐Heterocyclic Carbenes for Use in Synthesis and Catalysis

AbstractThe electrochemical generation of N‐heterocyclic carbenes (NHCs) offers a mild and selective alternative to traditional synthetic methods that usually rely on strong bases and air‐sensitive materials. The use of electrons as reagents results in an efficient and clean synthesis that enables the direct use of NHCs in various applications. Herein, the use of electrogenerated NHCs in organocatalysis, synthesis and organometallic chemistry is explored.magnified image

Organometallic Nanoparticles Ligated by NHCs: Synthesis, Surface Chemistry and Ligand Effects

Over the last 20 years, the use of metallic nanoparticles (MNPs) in catalysis has awakened a great interest in the scientific community, mainly due to the many advantages of this kind of nanostructures in catalytic applications. MNPs exhibit the characteristic stability of heterogeneous catalysts, but with a higher active surface area than conventional metallic materials. However, despite their higher activity, MNPs present a wide variety of active sites, which makes it difficult to control their selectivity in catalytic processes. An efficient way to modulate the activity/selectivity of MNPs is the use of coordinating ligands, which transforms the MNP surface, subsequently modifying the nanoparticle catalytic properties. In relation to this, the use of N-heterocyclic carbenes (NHC) as stabilizing ligands has demonstrated to be an effective tool to modify the size, stability, solubility and catalytic reactivity of MNPs. Although NHC-stabilized MNPs can be prepared by different synthetic methods, this review is centered on those prepared by an organometallic approach. Here, an organometallic precursor is decomposed under H2 in the presence of non-stoichiometric amounts of the corresponding NHC-ligand. The resulting organometallic nanoparticles present a clean surface, which makes them perfect candidates for catalytic applications and surface studies. In short, this revision study emphasizes the great versatility of NHC ligands as MNP stabilizers, as well as their influence on catalysis.

Recent Advances in Rare Earth Complexes Containing N-Heterocyclic Carbenes: Synthesis, Reactivity, and Applications in Polymerization

N-heterocyclic carbenes (NHCs) are ubiquitous ancillary ligands employed in metal-catalyzed homogeneous reactions and polymerization reactions. Of significance is the use of NHCs as the supporting ligand in second- and third-generation Grubbs catalysts for their application in olefin metathesis and ring-opening metathesis polymerization. While the applications of transition metal catalysts ligated with NHCs in polymerization chemistry are well-documented, the use of analogous rare earth (Ln = Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) catalysts in this area remains under-developed, despite the unique role of rare earth elements in regio- and stereo-specific (co)polymerization reactions. By using hetero-atom-tethered chelating NHCs and, more recently, the employment of other structurally related NHCs, NHC-ligated Ln complexes have proven to be promising and fruitful catalysts for selective polymerization reactions. This review summarizes the recent developments in the coordination chemistry of Ln complexes containing NHCs and their catalytic performance in polymerization.

Iron N-heterocyclic carbene complexes in homogeneous catalysis.

The development of homogeneous iron catalysts has been a prolific research field in recent years. Many catalytic reactions are no longer limited to noble metals. The use of N-heterocyclic carbenes (NHCs) as ancillary ligands has made substantial impact in noble metal catalysis and also started to gain popularity in iron catalysis in recent years. This review article surveys the recent literature on Fe-NHC-catalyzed chemical reactions, including C-C bond formation, reduction, and oxidation reactions.

Carboxylation Reactions with Carbon Dioxide Using N-Heterocyclic Carbene-Copper Catalysts.

The development of versatile catalyst systems and new transformations for the utilization of carbon dioxide (CO2 ) is of great interest and significance. This Personal Account reviews our studies on the exploration of the reactions of CO2 with various substrates by the use of N-heterocyclic carbene (NHC)-copper catalysts. The carboxylation of organoboron compounds gave access to a wide range of carboxylic acids with excellent functional group tolerance. The C-H bond carboxylation with CO2 emerged as a straightforward protocol for the preparation of a series of aromatic carboxylic esters and butenoates from simple substrates. The hydrosilylation of CO2 with hydrosilanes provided an efficient method for the synthesis of silyl formate on gram scale. The hydrogenative or alkylative carboxylation of alkynes, ynamides and allenamides yielded useful α,β-unsaturated carboxylic acids and α,β-dehydro amino acid esters. The boracarboxylation of alkynes or aldehydes afforded the novel lithium cyclic boralactone or boracarbonate products, respectively. The NHC-copper catalysts generally featured excellent functional group compatibility, broad substrate scope, high efficiency, and high regio- and stereoselectivity. The unique electronic and steric properties of the NHC-copper units also enabled the isolation and structural characterization of some key intermediates for better understanding of the catalytic reaction mechanisms.

N-Heterocyclic Carbenes in Materials Chemistry.

N-Heterocyclic carbenes (NHCs) have become one of the most widely studied class of ligands in molecular chemistry and have found applications in fields as varied as catalysis, the stabilization of reactive molecular fragments, and biochemistry. More recently, NHCs have found applications in materials chemistry and have allowed for the functionalization of surfaces, polymers, nanoparticles, and discrete, well-defined clusters. In this review, we provide an in-depth look at recent advances in the use of NHCs for the development of functional materials.

Well-Defined Palladium(II)-NHC Precatalysts for Cross-Coupling Reactions of Amides and Esters by Selective N-C/O-C Cleavage.

Transition-metal-catalyzed cross-coupling reactions represent a most powerful tool for the rapid construction of C-C and C-X bonds available to synthetic chemists. Recently, tremendous progress has been made in the burgeoning area of cross-coupling reactions of amides and esters enabled by regio- and chemoselective acyl C-X (X = N, O) cleavage using well-defined Pd(II)-NHC complexes. The use of N-heterocyclic carbenes as ligands in palladium-catalyzed cross-couplings permits reactions of amides and esters that were previously impossible using palladium or could be achieved only under harsh conditions. These reactions provide an attractive method to synthetic chemists to manipulate the traditionally inert amide and ester bonds with the broad cross-coupling generality inherent to palladium catalysis. Research in the area of cross-coupling of stable acyl electrophiles can be broadly categorized by the type of electrophile undergoing the cross-coupling. Recent studies have shown that cross-coupling of amides by transition-metal catalysis represents one of the most straightforward and wide-ranging ways of manipulating the classically inert amide bonds into generic acyl-metal intermediates that can be systematically exploited in cross-coupling reactions as a new paradigm in organic synthesis. The key to achieving high chemoselectivity of the process is control of amidic resonance (nN to πC═O* conjugation, rotation of ca. 15-20 kcal/mol in planar amides), enabling oxidative addition of the N-C amide bond to a metal in a rational and predictable manner. This mode of catalysis has been extended to C(acyl)-O cross-coupling reactions of aryl esters, where selective C-O bond cleavage is accomplished through a rational match of aryl ester electrophiles and nucleophilic metal catalysts. These two types of transition-metal-catalyzed cross-coupling reactions represent an attractive concept in synthetic chemistry because of the ubiquity of esters and amides as precursors in organic synthesis. Furthermore, the high stability of amides and esters provides unprecedented opportunities for orthogonal cross-coupling strategies in the presence of other electrophiles. In this Account, we highlight advances that have taken place in the past few years in the field of cross-coupling of amides and esters, focusing on both (1) the stereoelectronic properties of well-defined Pd(II)-NHC complexes that have been critical to realize this challenging cross-coupling manifold and (2) the role of the isomerization barrier of the acyl electrophiles undergoing the cross-coupling. In a broader sense, the chemistry described here provides a practical approach to functionalize common amide and ester functional groups in organic synthesis and establishes straightforward access to acyl-metal intermediates that enable nonconventional cross-coupling strategies.

N‐Heterocyclic‐Carbene‐Catalyzed Reactions of Nitroalkenes: Synthesizing Important Building Blocks

AbstractThe recent developments of N‐heterocyclic carbene (NHC)‐catalyzed acyl anion equivalent (Stetter reaction), homoenolate, and enolate reactions with reactive nitroalkenes as Michael acceptors are described. The unique strategies for NHC‐catalyzed C−C bond‐forming reactions using nitroalkenes for the synthesis of synthetic building blocks, in particular asymmetric approaches, are systematically presented. Advances in the single‐electron‐transfer reaction combined with the use of NHCs as organocatalysts are also discussed, with nitroalkenes acting as important coupling partners. This Focus Review brings together both the accomplishments and the future work needed in this important area.

NHC-Catalyzed Metathesis and Phosphorylation Reactions of Disulfides: Development and Mechanistic Insights.

The development of efficient methods for the metathesis and phosphorylation reactions of disulfide compounds is of widespread interest due to their important synthetic utility in polymer, biological, medicinal and agricultural chemistry. Herein, we demonstrate the use of N-heterocyclic carbenes (NHCs) as versatile organocatalysts to promote these challenging reactions under mild conditions. This metal- and oxidant-free protocol is operationally simple with very short reaction times. The interplay between the nucleophilicity and basicity of NHCs in these reactions were also elucidated by NMR studies and high-level ab initio calculations.

Cooperative Asymmetric Catalysis by N-Heterocyclic Carbenes and Brønsted Acid in γ-Lactam Formation: Insights into Mechanism and Stereoselectivity

Current developments in the burgeoning area of cooperative asymmetric catalysis indicate the use of N-heterocyclic carbenes (NHCs) in conjunction with other catalysts such as a Bronsted acid. Herein, mechanistic insights derived through a comprehensive DFT (M06-2X) computational study on a dual catalytic reaction between an enal and an imine leading to trans-γ-lactams, catalyzed by a chiral NHC and benzoic acid, is presented. In the most preferred pathway, we note that the NHC catalyst activates one of the reactants (enal) in the form of a Breslow intermediate, whereas the electrophilic partner (imine) is activated by the benzoic acid through protonation of the imino nitrogen. In this article, we focus on the origin of cooperative action of both catalysts as well as on the stereoselectivity by identifying the stereocontrolling transition states. The explicit and cooperative participation of the Bronsted acid and NHC lowers the energetic barrier both in the Breslow intermediate formation and in the stereoc...

Cross-Couplings Using Aryl Ethers via C-O Bond Activation Enabled by Nickel Catalysts.

Arene synthesis has been revolutionized by the invention of catalytic cross-coupling reactions, wherein aryl halides can be coupled with organometallic and organic nucleophiles. Although the replacement of aryl halides with phenol derivatives would lead to more economical and ecological methods, success has been primarily limited to activated phenol derivatives such as triflates. Aryl ethers arguably represent one of the most ideal substrates in terms of availability, cost, safety, and atom efficiency. However, the robust nature of the C(aryl)-O bonds of aryl ethers renders it extremely difficult to use them in catalytic reactions among the phenol derivatives. In 1979, Wenkert reported a seminal work on the nickel-catalyzed cross-coupling of aryl ethers with Grignard reagents. However, it was not until 2004 that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)-O bonds was appreciated with Dankwardt's identification of the Ni(0)/PCy3 system, which significantly expanded the efficiency of the Wenkert reaction. Application of the nickel catalyst to cross-couplings with other nucleophiles was first accomplished in 2008 by our group using organoboron reagents. Later on, several other nucleophiles, including organozinc reagents, amines, hydrosilane, and hydrogen were shown to be coupled with aryl ethers under nickel catalysis. Despite these advances, progress in this field is relatively slow because of the low reactivity of benzene derivatives (e.g., anisole) compared with polyaromatic substrates (e.g., methoxynaphthalene), particularly when less reactive and synthetically useful nucleophiles are used. The "naphthalene problem" has been overcome by the use of N-heterocyclic carbene (NHC) ligands bearing bulky N-alkyl substituents, which enables a wide range of aryl ethers to be coupled with organoboron nucleophiles. Moreover, the use of N-alkyl-substituted NHC ligands allows the use of alkynylmagnesium reagents, thereby realizing the first Sonogashira-type reaction of anisoles. From a mechanistic perspective, nickel-catalyzed cross-couplings of aryl ethers are at a nascent stage, in particular regarding the mode of activation of C(aryl)-O bonds. Oxidative addition is one plausible pathway, although such a process has not been fully verified experimentally. Nickel-catalyzed reductive cleavage of aryl ethers in the absence of an external reducing agent provides strong support for this oxidative addition process. Several other mechanisms have also been proposed. For example, Martin demonstrated a new possibility of the involvement of a Ni(I) species, which could mediate the cleavage of the C(aryl)-O bond via a redox-neutral pathway. The tolerance of aryl ethers under commonly used synthetic conditions enables alkoxy groups to serve as a platform for late-stage elaboration of complex molecules without any tedious protecting group manipulations. Aryl ethers are therefore not mere economical alternatives to aryl halides but also enable nonclassical synthetic strategies.

ChemInform Abstract: Recent Advances in Carbon Dioxide Capture, Fixation, and Activation by Using N‐Heterocyclic Carbenes

AbstractReview: 282 refs.