Reaction Of N-heterocyclic Carbene Research Articles

Synthesis and reactivity of N-heterocyclic carbene (NHC)-supported heavier nitrile ylides.

The synthesis and isolation of stable heavier analogues of nitrile ylide as N-heterocyclic carbene (NHC) adducts of phosphasilenyl-tetrylene [(NHC)(TerAr)Si(H)PE14(TerAr)] (E14 = Ge 1, Sn 2; TerAr = 2,6-Mes2C6H3, NHC = IMe4) are reported. The delocalized Si-P-E14 π-conjugation was examined experimentally and computationally. Interestingly, the germanium derivative 1 exhibits a 1,3-dipolar nature, leading to an unprecedented [3 + 2] cycloaddition with benzaldehyde, resulting in unique heterocycles containing four heteroatoms from group 14, 15, and 16. Further exploiting the nucleophilicity of germanium, activation of the P-P bond of P4 was achieved, leading to a [(NHC)(phosphasilenyl germapolyphide)] complex. Moreover, the [3 + 2] cycloaddition and the σ-bond activation by 1 resemble the characteristics of the classic nitrile ylide.

Synthesis and reactivity of N-heterocyclic carbene (NHC) gold-fluoroalkoxide complexes.

We disclose a novel series of N-heterocyclic carbene (NHC) gold complexes with varied steric and electronic properties, bearing fluorinated alkoxide anions. Early reactivity studies involving these synthons, lead to the synthesis of various complexes of relevance to gold chemistry and catalysis.

Persistent Radicals Derived from N-Heterocyclic Carbenes for Material Applications.

Persistent radicals are potential building blocks of novel materials in many fields. Recently, highly stable persistent radicals are considered to be within reach, thanks to several radical stabilization strategies such as spin delocalization and steric protection. N-Heterocyclic carbene (NHC)-derived substituents can be attached to a radical center for these purposes, as illustrated by numerous NHC-stabilized radicals reported in the last two decades.This Account describes our recent work on developing NHC-derived persistent radicals, as well as their prospective applications. Considering that NHCs not only stabilize radicals but also reversibly interact with gas molecules, in 2015 our group reported NHC-nitric oxide (NHC-NO) radicals produced by reversibly trapping nitric oxide (NO) radical gas in NHCs. The resultant compounds were loaded into biocompatible poly(ethylene glycol)-block-poly(caprolactone) (PEG-b-PCL) micelles and injected into tumor-bearing mice. Then, NO release was triggered by high-intensity focused ultrasound irradiation of the tumor tissue. Furthermore, the NHC-NO radicals could also serve as a platform to generate other organic radicals such as oxime ether or iminyl radicals. Apart from medicine-related applications, radicals stabilized by NHCs can be used as energy storage materials. In this context, the triazenyl radical containing two NHC units reported by our laboratory could be a cathode active material in batteries, as an organic alternative to LiCoO2. The subsequently prepared unsymmetrical triazenyl radical derivatives were applied as anolytes in nonaqueous all-organic redox flow batteries. In addition, a ferrocene-based redox flow battery anolyte was obtained by introducing NHC-derived substituents that effectively stabilize the ferrocenate derivatives previously reported only at low temperatures. The batteries containing NHC-supported radicals exhibited high energy efficiency and insignificant radical decomposition over multiple cycles. Finally, toward developing air-persistent organic radicals for flexible devices and MRI contrasting agents, we also highlight our recent air- and physiologically stable organic radicals derived from NHCs. Coordination of tris(pentafluorophenyl)borane to the NHC-NO radical produced a new radical cation that is stable in an organic solvent under air for several months. The readily accessible 1,2-dicarbonyl radical cations generated by the reaction of NHCs with oxalyl chloride are remarkably persistent even in an aqueous solution for several months. They are also highly stable even under physiological conditions, making them particularly attractive potential candidates for organic MRI contrast agents. We hope that this Account will serve as a guide for the future development of stable NHC-derived organic radicals and draw the attention of the synthetic community to their potential applications in material science.

A Thermally Stable Magnesium Phosphaethynolate Grignard Complex.

The 2-phosphaethynolate (OCP) anion has found versatile applications across the periodic table but remains underexplored in group 2 chemistry due to challenges in isolating thermally stable complexes. By rationally modifying their coordination environments using 1,3-dialkyl-substituted N-heterocyclic carbenes (NHCs), we have now isolated and characterized thermally stable, structurally diverse, and hydrocarbon soluble magnesium phosphaethynolate complexes (2, 4Me, and 8-10), including the novel phosphaethynolate Grignard reagent (2iPr). The methylmagnesium phosphaethynolate and magnesium diphosphaethynolate complexes readily activate dioxane with subsequent H-atom abstraction to form [(NHC)MgX(μ-OEt)]2 [X = Me (3) or OCP (8 and 9)] complexes. Their reactivities increased with the Lewis acidity of the Mg2+ cation and may be attenuated by Lewis base saturation or a slight increase in carbene sterics. Solvent effects were also investigated and led to the surreptitious isolation of an ether-free sodium phosphaethynolate (NHC)3Na(OCP) (6), which is soluble in aromatic hydrocarbons and can be independently prepared by the reaction of NHC and [Na(dioxane)2][OCP] in toluene. Under forcing conditions (105 °C, 3 days), the magnesium diphosphaethynolate complex (NHC)3Mg(OCP)2 (10) decomposes to a mixture of organophosphorus complexes, among which a thermal decarbonylation product [(NHC)2PI][OCP] (11) was isolated.

DFT Investigation of Hydrogen Atom Abstraction from NHC-Boranes by Methyl, Ethyl and Cyanomethyl Radicals-Composition and Correlation Analysis of Kinetic Barriers.

Understanding the hydrogen atom abstraction (HAA) reactions of N-heterocyclic carbene (NHC)-boranes is essential for extending the practical applications of boron chemistry. In this study, density functional theory (DFT) computations were performed for the HAA reactions of a series of NHC-boranes attacked by •CH2CN, Me• and Et• radicals. Using the computed data, we investigated the correlations of the activation and free energy barriers with their components, including the intrinsic barrier, the thermal contribution of the thermodynamic reaction energy to the kinetic barriers, the activation Gibbs free energy correction and the activation zero-point vibrational energy correction. Furthermore, to describe the dependence of the activation and free energy barriers on the thermodynamic reaction energy or reaction Gibbs free energy, we used a three-variable linear model, which was demonstrated to be more precise than the two-variable Evans–Polanyi linear free energy model and more succinct than the three-variable Marcus-theory-based nonlinear HAA model. The present work provides not only a more thorough understanding of the compositions of the barriers to the HAA reactions of NHC-boranes and the HAA reactivities of the substrates but also fresh insights into the suitability of various models for describing the relationships between the kinetic and thermodynamic physical quantities.

A Nickel Complex Containing a Pyramidalized, Ambiphilic Pincer Germylene Ligand.

Reaction of N-heterocyclic carbene (NHC)-stabilized PGeP-type germylene Ge{o-(PiPr2 )C6 H4 }2 ⋅Me IiPr (1) (Me IiPr=1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) with Ni(cod)2 gave pincer germylene complex Ni[Ge{o-(PiPr2 )C6 H4 }2 ](Me IiPr) (2), in which the Ge center of 2 is significantly pyramidalized. Theoretical calculation on 2 predicted the ambiphilicity of the germanium center, which was confirmed by reactivity studies. Thus, complex 2 reacted with both Lewis base Me IMe (Me IMe=1,3,4,5-tetramethylimidazol-2-ylidene) and Lewis acid BH3 ⋅SMe2 at the germanium center to afford the adducts Ni[Ge{o-(PiPr2 )C6 H4 }2 ⋅Me IMe](Me IiPr) (3) and Ni[Ge{o-(PiPr2 )C6 H4 }2 ⋅BH3 ](Me IiPr) (4), respectively. Furthermore, the former was slowly converted to dinuclear complex Ni2 [Ge{o-(PiPr2 )C6 H4 }2 ]2 (Me IMe)2 (5) at room temperature. Complex 5 can be regarded as a dimer of the Me IMe analog of 2 with a Ni-Ge-Ge-Ni linkage.

Reaction Mechanisms on Unusual 1,2-Migrations of N-Heterocyclic Carbene-Ligated Transition Metal Complexes.

Unusual 1,2-migration reactions of N-heterocyclic carbene (NHC) on transition metals were investigated using density functional theory calculations. Our results reveal that the electronic properties, ring strain of the four-membered ring, and aromaticity of NHC play crucial roles in the thermodynamics of such a 1,2-migration. Further studies show that changing the methylene on the metal center in the reactant with a more electronegative group (NH or O) will lead to the formation of products with nitrogen coordinating to the metal center, whereas other groups (BH, CF2 , and SiH2 ) will make such a 1,2-migration reverse. In addition, the reversed rearrangement of 1,2-boron, silyl migration could be thermodynamically and kinetically favorable.

Influence of N-Substitution on the Formation and Oxidation of NHC–CAAC-Derived Triazaalkenes

We have studied the effect of N-substitution on the course of the reaction of imidazolium triflate. The reaction of N-heterocyclic carbene with N-tBu-substituted pyrrolinium triflate afforded 2-(pyrrolidin-2-yl)-imidazolium triflate, 3R. Treatment of 3R with potassium bis(trimethylsilyl)amide (KHMDS) leads to either the dealkylation product 4 or the deprotonation product, triazaalkene 5, depending on the N-substitution at the imidazolium moiety. Density functional studies using the B3LYP/TZVP setup have been employed to explore various pathways for the dealkylation reaction and the calculated energies support the dealkylation by a large energy margin compared to the deprotonatation process. Theoretical calculations revealed that dealkylation reaction is thermodynamically more favorable than deprotonation. The triazaalkene 5 could be oxidized by AgOTf to the corresponding radical cation 6 and dication 7 in-situ. While 6 and 7 could not be isolated, the formation of the former is inferred by electron paramagnetic resonance spectroscopy and its abstraction of a H-atom to afford 3Me. Similarly, the formation of the dication 7 is inferred by its ready elimination of isobutylene affording 8.

5- Endo Cyclizations of NHC-Boraallyl Radicals Bearing Ester Substituents: Characterization of Derived 1,2-Oxaborole Radicals and Boralactones.

EPR studies of radical hydrogen abstraction reactions of N-heterocyclic carbene (NHC) complexes of alkenylboranes bearing two ester substituents revealed not the expected boraallyl radicals but instead isomeric 1,2-oaxborole radicals. Such radicals are new, and DFT calculations show that they arise from the initially formed boraallyl radicals by a rapid, exothermic 5- endo cyclization. These spectroscopic and computational discoveries prompted a series of preparative experiments that provided access to a novel family of robust NHC-boralactones. A one-pot procedure was developed to access the boralactones directly from an NHC-borane (NHC-BH3) and dimethyl acetylenedicarboxylate.

Reactivity of N-heterocyclic carbene, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, towards heavier halogens (Br2 and I2)

Reactivity of N-heterocyclic carbene, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, towards heavier halogens (Br2 and I2)

Synthesis of N-heterocyclic carbene boranes via silver N-heterocyclic carbene complexes

The reaction of N-heterocyclic carbene (NHC) complexes of silver with BH3 or BEt3 was investigated. On treatment of IiPr·AgCl (1-AgCl) (IiPr=1,3-diisopropylimidazol-2-ylidene) with two equivalents of NaBH4-free BH3·THF (purified BH3·THF) in THF at room temperature for 2h, IiPr·BH3 complex (1-BH3) was obtained in excellent yield (96%). In the reaction of various silver NHC complexes with purified BH3·THF, the corresponding NHC·BH3 complexes were obtained in moderate to good yields. The reaction of 1-AgCl with two equivalents of BEt3, instead of BH3, afforded IiPr·BEt3 complex (1-BEt3) in 86% yield. This procedure enabled the preparation of BEt3-adducts of imidazol- and benzimidazol-2-ylidenes.

Reversible Oxidative Addition at Carbon.

The reactivity of N-heterocyclic carbenes (NHCs) and cyclic alkyl amino carbenes (cAACs) with arylboronate esters is reported. The reaction with NHCs leads to the reversible formation of thermally stable Lewis acid/base adducts Ar-B(OR)2 ⋅NHC (Add1-Add6). Addition of cAACMe to the catecholboronate esters 4-R-C6 H4 -Bcat (R=Me, OMe) also afforded the adducts 4-R-C6 H4 Bcat⋅cAACMe (Add7, R=Me and Add8, R=OMe), which react further at room temperature to give the cAACMe ring-expanded products RER1 and RER2. The boronate esters Ar-B(OR)2 of pinacol, neopentylglycol, and ethyleneglycol react with cAAC at RT via reversible B-C oxidative addition to the carbene carbon atom to afford cAACMe (B{OR}2 )(Ar) (BCA1-BCA6). NMR studies of cAACMe (Bneop)(4-Me-C6 H4 ) (BCA4) demonstrate the reversible nature of this oxidative addition process.

Reaction of N-heterocyclic carbene (NHC) with different HF sources and ratios – A free fluoride reagent based on imidazolium fluoride

Treatment of N-heterocyclic carbene (1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene; (LDipp)) with different sources of hydrofluoric acid (Et3N∙3HF, anhydrous hydrofluoric acid and KHF2) in 1:1, 1:2, 1:3 ratios affords [(LDipp)H]+[F]− (1), [(LDipp)H]+[(HF)F]− (2) and [(LDipp)H]+[(HF)2F]− (3) salts respectively. Different fluoride sources all yield the same products, but ease of manipulation and isolation can influence the choice in the future use.Compound (1), which shows characteristics of a free fluoride reagent, can be obtained with good yield and without the contaminants usually present in such compounds. All products were characterized by X-Ray crystallography, NMR spectroscopy and free fluoride (Ff−) chemical analysis.

Carbene-induced synthesis of the first borironium cations using the [(η(5)-C5Me5)Fe(CO)2](-) anion as an unlikely leaving group.

Reaction of N-heterocyclic carbenes with ferroborirene complex [{(η(5)-C5Me5)Fe(CO)2}{BC2(SiMe3)2}] results in heterolytic Fe-B bond cleavage, yielding borironium ions, a new class of boron-containing heterocycles. The reaction rests on the surprising ability of the reactive [(η(5)-C5Me5)Fe(CO)2](-) anion to act as a leaving group. The properties of these species were investigated by multinuclear NMR spectroscopy, as well as single-crystal X-ray diffraction.

Why do N-heterocyclic carbenes and silylenes activate white phosphorus differently?

We explored the possible reaction of three model carbenes and two model silylenes with white phosphorus leading to insertion, bis-adduct, and tris-adduct products. The energetics of the calculated mechanisms are in accordance with the experimental observations explaining key features like carbene–P4 ratio-dependent reactivity of carbonyl decorated bisamidocarbene and cyclic alkyl-amino carbene. The analysis of the bonding motif of C–P and Si–P bonds in the key intermediate revealed the importance of double-bond and donor–acceptor resonance structures. We found correlation between the σ-donor and π-acceptor strength of investigated carbenes and silylenes and their reactivity with white phosphorus. The combination of low σ-donor and high π-acceptor strength in N-heterocyclic silylene (NHSi) indicated the instability of the key intermediate, bis-adduct, and tris-adduct products and the stability of the insertion product, while high σ-donor and low π-acceptor strength of N-heterocyclic carbene (NHC) resulted in reversed stability order of the previous compounds explaining the different reaction of NHC and NHSi with white phosphorus. Donor-stabilized silylene (DSSi) has high σ-donor and low π-acceptor strength similar to NHC supporting their similar reactivity and the difference between NHSi and DSSi.

The addition reactions between N-heterocyclic carbenes and fullerenes (C60 and C70): a density functional study

The potential energy surfaces for the addition reactions of N-heterocyclic carbene with C60 and C70 are characterized in detail, using density functional theory (M06-2X). These theoretical investigations strongly suggest that the one-point attack in formation of the single-bonded adduct is the most favorable reaction pathway at room temperature, rather than the production of the cycloadduct with a three-membered ring, from both kinetic and thermodynamic viewpoints. Also, this theoretical work indicates that the dispersion interactions cannot make the contributions to determine the regioselective formations for these NHC–fullerene Lewis acid–base adducts. These theoretical conclusions are consistent with the available experimental observations.

Reaction of N-heterocyclic carbenes with chalcones leading to the synthesis of deoxy-Breslow intermediates in their oxidized form.

The synthesis of deoxy-Breslow intermediates in their oxidized form has been developed via the reaction of N-heterocyclic carbenes (NHCs) with chalcones. Moreover, the initial tetrahedral adduct formed from the 1,4-addition of NHCs to chalcones is also isolated.

Reaction of N-heterocyclic carbenes with 13-vertex closo-carboranes: synthesis and structural characterization of zwitterionic salts of 13-vertex nido-carboranes

13-Vertexcloso-carboranes and N-heterocyclic carbenes undergo a fast acid–base reaction to generate intermediates that are slowly converted to the final products.

A stable N-heterocyclic carbene organocatalyst for hydrogen/deuterium exchange reactions between pseudoacids and deuterated chloroform.

It was observed that the stable and commercially available N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, the so-called IDipp, catalyzes hydrogen/deuterium exchange reactions between pseudoacids and chloroform-d1, while the analogous saturated NHC 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene, the so-called SIMes, is inefficient for the same transformation. Experimental and computational DFT studies allowed these differences of reactivity to be attributed to the relative stability of the corresponding azolium–trichloromethyl anion ion pairs: in the former case, the complex evolves toward dissociation of the ions to produce an aromatic azolium cation and a basic trichloromethyl anion, while in the latter case, it evolves by ion recombination to give the product of formal carbene C–H insertion into the C–H bond of chloroform. These results provide a rationale for some early intuitions and observations of Wanzlick, Arduengo, and others on the reactivity of NHCs with chloroform as well as a simple organocatalytic method for the deuteration of pseudoacids (pKa,DMSO = 14–19) with chloroform-d1.

Tunneling assists the 1,2-hydrogen shift in N-heterocyclic carbenes.

At room temperature, 1,2-hydrogen-transfer reactions of N-heterocyclic carbenes, like the imidazol-2-ylidene to give imidazole is shown to occurr almost entirely (>90 %) by quantum mechanical tunneling (QMT). At 60 K in an Ar matrix, for the 2, 3-dihydrothiazol-2-ylidene→thiazole transformation, QMT is shown to increase the rate about 10(5) times. Calculations including small-curvature tunneling show that the barrier for intermolecular 1,2-hydrogen-transfer reaction is small, and QMT leads to a reduced rate of the forward reaction because of nonclassical reflections even at room temperature. A small barrier also leads to smaller kinetic isotope effects because of efficient QMT by both H and D. QMT does not always lead to faster reactions or larger KIE values, particularly when the barrier is small.