Carbene Species Research Articles

Rhenium-Catalyzed Cyclization via 1,2-Iodine and 1,5-Hydrogen Migration for the Synthesis of 2-Iodo-1H-indenes.

A rhenium complex catalyzed the formation of 2-iodo-1H-indene derivatives through iodine and hydrogen migration of 3-iodopropargyl ethers. The reaction proceeded via generation of 1-iodoalkenylrhenium carbene species by sequential 1,2-iodine and 1,5-hydrogen shifts with readily available precursors under neutral conditions. The reaction mechanism and the reactivity of the generated alkenylcarbene species were also investigated.

Cu(I)-Catalyzed Three-Component Reaction of α-Diazo Amide with Terminal Alkyne and Isatin Ketimine via Electrophilic Trapping of Active Alkynoate-Copper Intermediate.

A three-component reaction between terminal alkyne, α-diazo amide, and isatin ketimine is realized by utilizing copper catalysis. A series of alkynyl-containing 3,3-disubstituted oxindoles were synthesized with high efficiency and diastereoselectivity under mild reaction conditions. This transformation is proposed to proceed through a Mannich-type trapping of an alkynoate copper intermediate derived from terminal alkyne and copper carbene species.

Synthesis of nucleoside units possessing photoreactive diazirine groups on the major and minor groove faces

In this work, we developed and examined photoreactive nucleoside units, which are chemical probes to investigate the interaction between nucleic acids and proteins. Starting with 6-chloro-7-iodo-7-deazapurine derivative 5, 7-(3-oxobutyl)-7-deazaadenosine derivative 8 was prepared via a palladium-catalyzed reaction with 3-buten-2-ol. Then, the carbonyl group of 8 was converted into a diazirinyl group to provide the desired Dia7C7A 3. In a similar manner, Dia2A 4 was prepared from 2 to iodoadenosine derivative 11. The resulting 3 and 4 were confirmed to form chemically active carbene species via photo-irradiation.

N-Heterocyclic Germylenes: Structural Characterisation of Some Heavy Analogues of the Ubiquitous N-Heterocyclic Carbenes

The X-ray crystal structures of three N-heterocyclic germylenes (NHGes) have been elucidated including the previously unknown 1,3-bis(2,6-dimethylphenyl)diazagermol-2-ylidene (1). In addition, the X-ray crystal structures of the previously synthesised 1,3-bis(2,4,6-trimethylphenyl)diazagermol-2-ylidene (2) and 1,3-bis(2,6-diisopropylphenyl)diazagermol-2-ylidene (3) are also reported. The discrete molecular structures of compounds 1 to 3 are comparable, with Ge-N bond lengths in the range 1.835-1.875 Å, while the N-Ge-N bond angles range between 83.6 and 85.2°. Compound 2 was compared to the analogous N-heterocyclic carbene species, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes). The major geometrical difference observed, as expected, was the bond angle around the divalent group 14 atom. The N-Ge-N bond angle was 83.6° for compound 2 versus the N-C-N bond angle of 101.4° for IMes. The Sn equivalent of (1), 1,3-bis(2,6-dimethylphenyl)diazastannol-2-ylidene (4), has also been synthesised and its crystal structure is reported here. In order to test their suitability as ligands, compounds 1 to 3 were reacted with a wide range of transition metal complexes. No NHGes containing metal complexes were observed. In all cases the NHGe either degraded or gave no reaction.

Cerium-carbon dative interactions supported by carbodiphosphorane.

A set of complexes containing dative interactions between a rare-earth metal and carbon are reported. Complex 2, Br3Ce(CDP)(THF), with a Ce←C bond was synthesized by the reaction of CeBr3 with a carbon(0) ligand, carbodiphosphorane (CDP). More significantly, a trivalent cerium complex 3, [BrCe(CDP)2](BPh4)2, with two σ dative interactions C→Ce←C was also isolated, which represents an unusual example of two dative interactions formed with the same atom in a molecule. Furthermore, π donation by the second lone-pair electrons of the CDP ligand is rather weak. Single-crystal X-ray diffraction shows that the Ce-C bond lengths in these complexes are comparable with those in cerium(iii)-carbene species. Density functional theory calculations support the dative interaction formation in these complexes and the strength of σ-donation in 3 is stronger than that in 2.

Double dative bond between divalent carbon(0) and uranium

Dative bonds between p- and d-block atoms are common but species containing a double dative bond, which donate two-electron pairs to the same acceptor, are far less common. The synthesis of complexes between UCl4 and carbodiphosphoranes (CDP), which formally possess double dative bonds Cl4U⇇CDP, is reported in this paper. Single-crystal X-ray diffraction shows that the uranium−carbon distances are in the range of bond lengths for uranium−carbon double bonds. A bonding analysis suggests that the molecules are uranium−carbone complexes featuring divalent carbon(0) ligands rather than uranium−carbene species. The complexes represent rare examples with a double dative bond in f-block chemistry. Our study not only introduces the concept of double dative bonds between carbones and f-block elements but also opens an avenue for the construction of other complexes with double dative bonds, thus providing new opportunities for the applications of f-block compounds.

Enantioselective Oxidative Cyclization/Mannich Addition Enabled by Gold(I)/Chiral Phosphoric Acid Cooperative Catalysis

An enantioselective Mannich-type reaction of 3-butynol and nitrones is described, which affords dihydrofuran-3-ones in good yields and with excellent enantioselectivities. The reaction is initiated by gold-catalyzed alkyne oxidation and modification of the resulting gold carbene species with a tethered hydroxy group to form enolate species; the reaction terminates with an enantioselective Mannich-type addition with the assistance of chiral phosphoric acid (CPA) and hydrogen bonding. This novel pattern of alkyne transformation involving chemical bond cleavage, and a fragment modification and reassembly process, provides an atom- and step-economic method, and is the first example of cooperative asymmetric catalysis in gold-catalyzed alkyne oxidations via an α-oxo gold carbene route.

Selective Chain-End Functionalization of Polar Polyethylenes: Orthogonal Reactivity of Carbene and Polar Vinyl Monomers in Their Copolymerization with Ethylene.

Pd(II)-catalyzed copolymerization of ethylene, carbene species, and polar vinyl monomers is successfully developed for the first time to obtain chain-end-functionalized polar polyethylenes, with selective distribution of the polar vinyl monomers within the main chain and carbene at the chain-end. Notably, >99% chain-end-capping with the carbene species can be achieved under the optimized conditions. Mechanistic investigations suggest that the carbene precursor reacts with the generated alkyl palladium complex to terminate the growing chain-end and regenerate the catalyst.

Palladium(0)-Catalyzed Intramolecular Cascade Cyclization of Methylenecyclopropanes.

A Pd(0)-catalyzed cascade cyclization of methylenecyclopropanes (MCPs) involving an intramolecular Heck-type reaction and β-H eliminations has been disclosed in this paper. The reaction proceeds smoothly through an unprecedented ring-opening pattern of MCPs via a cyclopropene intermediate and a vinylpalladium carbene species seemingly, furnishing spirocyclic compounds containing fluorene and 1,2-dihydronaphthalene moieties in moderate to good yields.

Use of Cyclopropane as C1 Synthetic Unit by Directed Retro-Cyclopropanation with Ethylene Release.

Cyclopropanation of alkenes is a well-established textbook reaction for the synthesis of cyclopropanes, where a "high-energy" carbene species is exploited to drive the reaction forward. However, little attention has been focused toward molecular transformations involving the reverse reaction, retro-cyclopropanation (RC). This is because of difficulties associated with both cleaving the two geminal C-C single bonds and exploiting the generated carbenes for further transformations in an efficient and selective manner. Here, we report that a molybdenum-based catalytic system overcomes the above challenges and effects the RC of cyclopropanes bearing a pyridyl group with the release of ethylene (alkene) and the subsequent intramolecular cyclization leading to pyrido[2,1- a]isoindoles. The reaction allows for the uncommon use of cyclopropanes as C1 synthetic units in contrast to most conventional reactions in which cyclopropanes are used as C3 synthetic units. We anticipate that this new strategy will pave the way for C1 cyclopropane chemistry.

Copper-Catalyzed Syntheses of 3-Allyl-3-arylthioindolin-2-imines and 3-Allenyl-3-arylthioindolin-2-imines from 3-Diazoindolin-2-imines

3-Allyl-3-arylthioindolin-2-imines and 3-allenyl-3-arylthioindolin- 2-imines were synthesized via the copper-catalyzed reaction of 3-diazoindolin-2-imines with allyl and propargyl aryl sulfides, respectively. The formation of a sulfonium ylide through the reaction of allyl or propargyl aryl sulfides with copper carbene species generated from 3-diazoindolin-2-imines and subsequent [2,3]-sigmatropic rearrangement should be involved in the cascade process. The procedure is general and highly efficient for the construction of these 3,3-disubstituted indoline derivatives.

Recent Applications of α-Carbonyl Sulfoxonium Ylides in Rhodium- and Iridium-Catalyzed C–H Functionalizations

Sulfoxonium ylides are a special type of sulfur ylides that serve as new C1 or C2 synthons recently developed for use in C–H functionalization to access acylmethylated or cyclized compounds through the formation of metal carbene species. Many excellent works have reported the syntheses of various useful skeletons from these versatile synthons. These developments have not previously been completely investigated or reviewed. In this review, we summarize recent advances in the use of α-carbonyl sulfoxonium ylides in C–H functionalizations, including ortho-C–H acylmethylation reactions and ortho-C–H activation/cyclization reactions. Table of Contents 1 Introduction2 Ortho-C–H Acylmethylation Reactions3 Ortho-C–H Activation/Cyclization Reactions3.1 Ortho-C–H Activation/Cyclization of Anilines and Enamines3.2 Ortho-C–H Activation/Cyclization of Azobenzenes3.3 Ortho-C–H Activation/Cyclization of N-Methoxybenzamide3.4 Ortho-C–H Activation/Cyclization of Imines3.5 Ortho-C–H Activation/Cyclization of N-Azoloimines3.6 Ortho-C–H Activation/Cyclization of Benzoylacetonitriles3.7 Ortho-C–H Activation/Cyclization of Benzoyl Sulfoxonium Ylides4 Conclusion

Initiation of heterogeneous Schrock-type Mo and W oxide metathesis catalysts: A quantum thermochemical study

Three mechanistic pathways were explored theoretically to study the electronic features and thermodynamics behind the initiation of silica-grafted molybdenum and tungsten oxide metathesis pre-catalysts in light olefins (ethylene and propylene) to form Schrock-type carbene structures. At 298 K and 1 atm, the investigated activation process was found to be exothermic for all but one of the carbene species, where the pathway involving a secondary carbene center and liberating acetone as a byproduct was more favorable (by about 10 kcal/mol) than the process involving a primary carbene center and evolving propionaldehyde. The most exothermic carbene to form (−20.9 kcal/mol) had its both propylidene and propoxy groups bonded through their secondary carbon atoms. A competing pathway suggested for an ethylene feedstock and tungsten-based catalyst, which involved the production of acetaldehyde was also viable. The generation of carbene species from the W-based pre-catalyst was less exothermic than the Mo-based pre-catalyst, however. The computational data with the activation pathways at hand stressed the benefits of initiation at low temperatures, the presence of adjacent trapping heterogeneities for the acetone or propanal by-products, and the beneficial role of the presence of an isopropoxy ligand. The localized-orbital locator maps indicated the polar covalent characteristics of the metal–carbene bonds, which were polarized towards the C atom. The analysis of the density of states indicated the destabilization of the highest occupied molecular orbitals (HOMOs) of the pre-catalysts upon carbene generation, where the alkylidene fragment and transition metal both contributed to the HOMO of the carbene complex.

Experimental and Computational Studies on Stepwise [3+2]‐Cycloadditions of Diaryldiazomethanes with Electron‐Deficient Dimethyl (E)‐ and (Z)‐2,3‐Dicyanobutenedioates

Electron‐deficient dimethyl (E)‐ and (Z)‐2,3‐dicyanobutenedioates (dimethyl dicyanofumarate and dicyanomaleate, respectively) react with diaryldiazomethanes at room temperature under spontaneous evolution of N2. The type of the products strongly depends on the structure of the diazo compound. Whereas diphenyldiazomethane and its bis(4‐methoxy) derivative yield cyclopropanes, sterically crowded 5‐diazo‐5H‐dibenzo[a,d]cycloheptane derivatives afford either the dimer of the carbene formed via N2 elimination or the adduct of the carbene onto the starting diazo compound. The course of the studied reactions is rationalized by stepwise mechanisms initiated by the formation of a C–N bond. A cascade of reactions leads to the corresponding cyclopropanes or to release of a carbene species. The formation of a pyrazole via [3+2]‐cycloaddition (32CA) is observed only in reactions with (trimethylsilyl)diazomethane, which behaves similar to the parent diazomethane. The proposed mechanisms were analyzed computationally using the DFT method.

Cu(I)-Catalyzed Three-Component Reaction of Diazo Compound with Terminal Alkyne and Nitrosobenzene for the Synthesis of Trifluoromethyl Dihydroisoxazoles

A Cu(I)-catalyzed three-component reaction of terminal alkynes, trifluoromethyl diazo compounds, and nitrosoarenes was developed. With this method, a series of trifluoromethyl-substituted dihydroisoxazoles were effectively synthesized in high yields under mild reaction conditions. This transformation is proposed to proceed through an electrophilic trapping of the copper carbene species generated from terminal alkynes and diazo compounds by nitrosobenzenes.

(Invited) Synthesis and Redox Property of Sumanenyl Trication

Sumanene, a bowl-shaped aromatic molecule, possesses the partial structure of C60 and shows unique structural and physical properties based on its curved pi-conjugated system. One of the characteristic features of sumanene is the presence of three benzylic carbons, which allow us to generate the corresponding cation, anion, and carbene species. Here we report the successful generateon, isolateon and redox property of sumanenyl tri-cations. Sumanenyl tri-cations (1) were obtained in high yield by acid-triggered generateon o\\from the corresponding hydroxyl-substituted sumanene derivative as a precursor. 1 reacted with the hydride donor, giving a tri-phenyl sumanene (2, 2’) and quinoidal sumanene (3’) in the presence and the absence of acid, respectively. Cyclic voltammetry revealed multi-step redox property of 1. Reductive wave at −1.28 V was observed as 2 electrons reduction without acid. In contrast, reductive wave at −1.17 V and −1.68 V were observed as 1 electron reduction with acid. Figure 1

Simulations and Experiments of the Kinetics of the Electrochemical Double Layer in Ionic Liquids

Ionic liquids are an interesting class of electrolytes both from a fundamental scientific standpoint and from an applications standpoint due to a number of relevant applications like batteries, supercapacitors and solar cells. Even though the constituents of ionic liquids are only ions, the conductivities are known to be pretty low. The suggested reasons for this low conductivity are low mobility due to high viscosity and the existence of most ions as ion pairs. Even though they have low conductivities, their electrochemical potential window and their low to non-existent vapor pressures make them very attractive as electrolytes. Because ionic liquids have no measurable vapor pressure, in-situ X-Ray Spectroscopy (XPS) can be performed directly on the ionic liquids during electrochemical experiments. This is not possible with more conventional electrolytes since any other electrolytic solution would not be conducive to running experiments inside the ultra-high vacuum (UHV) chamber. We have been doing experiments investigating both Faradaic and non-Faradaic aspects of electrochemical experiments on ionic liquids inside the XPS chamber. On the Faradaic side we have recently shown that the reduction of imidazolium based ionic liquids can yield stable carbene species (Aydogan-Gokturk et.al. New Journal of Chemistry 18(2017), 10299-10304 and Aydogan-Gokturk et.al. Electrochimica Acta 234(2017), 37-42) and that gold nanoparticles can be oxidatively synthesized starting from metal electrodes (Camci et.al. ACS Omega, 2(2017), 478-486). On the non-Faradaic front, investigations of the electrochemical double layer revealed that the applied potential has transient effects that are sensed unexpectedly far away from the electrode surface (Camci et.al. Phys. Chem. Chem. Phys. 18(2016)28434-28440). Specifically, our experiments indicate that the effects of the applied potential are felt up to millimeters away from the electrode surface during the transients. These transients can last hundreds of seconds and dominate the response. The current contribution is going to elaborate more on the unexpected electrochemical double layer effects. Even though the electrochemical double layer in electrolytes is well understood since the days of Gouy-Chapman-Stern model development, the double layer in the ionic liquid media is known to be somewhat different. There is a sizable body of recent modeling literature on the electrochemical double layer in ionic liquids. For example, work by Bazant et.al. (Phys. Rev. Lett. 106(2011) 046102), Lee et.al.(Phys. Rev. Lett. 115(2015)106101) and Gavish et.al.(J. Phys. Chem. Lett. 7(2016), 1121-1126) consider continuum type models of various sorts to model the behavior of the anions and the cations in great detail. The results indicate that there is some layering behavior that are either close to the electrode surface or throughout the region between the electrodes. The models used, though very detailed and thorough neglect ion pairing and thermal fluctuations. The effect of ion pairing is a crucial part of the explanation of the low conductivity of ionic liquids. On the other hand, thermal fluctuations are a necessary part of the conventional explanation of the diffuse double layer. In most cases, the models developed predict a layered steady state structure and also predict that the Debye length would be on the order of 10-20 times the size of a monolayer for most cases. Our experiments indicate that the effect of the applied potential is felt way farther away from the electrode in the transient times. We have developed a simpler modeling framework that model diffusion, convection and ion pairing using simple algebraic expressions on a simple grid that is set up. This framework involves setting up a grid between the two electrodes and starting with a homogeneous ionic liquid. At every time step, the algorithm iterates over the grid and treats diffusion, migration and ion pairing separately using simple constructs. Diffusion is simply handled by a random number generator that determine which way the ions will move, if at all. Then, the potential difference between neighboring points of the grid is used to evaluate the electric fields, which is used to then treat migration. Finally, for every position on the grid, a simple chemical equilibrium calculation is employed to solve for the number of ions that pair up. Using this framework to model the behavior of the ionic liquids and tuning the parameters of the simulation based on the results of transient measurements inside the XPS chamber using Squarewave applied potentials, we will report behavior of the electrochemical double layer in ionic liquids and insights about various parameters of ionic liquids such as ion-pairing constants, mobilities and diffusion coefficients. Figure 1

Development of Broad‐Based Labeling Reagents for Peptide and Protein Footprinting

Interactions between macromolecules in living organisms are governed by fundamental biophysical principles. Different methods to study these biophysical properties exist; including footprinting. Footprinting refers to the structural probing of interaction between macromolecules using chemical reactions ranging from HDX to reactive species such as free radicals and carbenes. Modern footprinting methods allows for a fast, specific, and precise determination of proteins' structure, interaction sites, conformational changes, folding, misfolding, and binding affinity. The complete understanding of these, in‐vitro and in the cell, is crucial for drug development and antibody synthesis for therapeutics and diagnostics. These advances contribute to the understanding of the human proteome. Methods for determining a protein footprint include Mass Spectrometry (MS), which is advantageous given its sensitivity. Covalent modification of amino acid residues coupled with MS has been useful in characterizing non‐membrane and membrane proteins; a field where current biophysical techniques are limited. Covalent modification can be achieved via Fast Photochemical Oxidation of Proteins (FPOP) using radical chemistry. Residue labeling using current radical species lacks generality or broad reactivity among amino acids. Thus, the development of novel chemical labeling methods that increases amino acid labeling are needed. To implement this, we propose the use of carbene species (double radicals), trifluoro‐methyl radicals, and chloride cations. Carbene compounds will be generated via FPOP from diazirine precursors, which were synthesized from ketone precursors. The Togni's Reagent will be used as a precursor for covalent modification through trifluoromethyl radicals and Palau's reagent will be used for modification through chloride cations. If a robust footprinting method is developed to further understand protein biophysics it would lead to further advances in the study of protein folding, protein‐protein interactions, and drug development.Support or Funding InformationAmgen Foundation. Michael Gross's Laboratory. NIH/NIGMS Biomedical Mass Spectrometry Resource.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Catalytic Dearomative Spirocyclization via Gold Carbene Species Derived from Ynamides: Efficient Synthesis of 2-Azaspiro[4.5]decan-3-ones.

An intramolecular catalytic dearomatization of phenols via gold carbene species proceeded to provide 2-azaspiro[4.5]decan-3-ones. The use of NHC ligand and water as a co-solvent was critical for achieving high reactivity. This reaction did not require hazardous diazo compounds as carbene sources and proceeded even under air. The obtained spirocyclic product could be readily transformed into a gabapentin derivative by hydrogenation and deprotection.

Investigating the mechanism through which ionic liquids initiate the polymerisation of epoxy resins

The mechanism of reaction between 1-ethyl-3-methylimidazolium acetate and the difunctional diglycidyl ether of bisphenol A (DGEBA) is explored using thermal and spectroscopic methods. Investigation of the 1,3-dialkylimidazolium based ionic liquids comprising the common cation (1-ethyl-3-methylimidazolium) and different anions (acetate, diethyl phosphate, dicyanamide or thiocyanate) via thermogravimetric analysis revealed 1-ethyl-3-methylimidazolium acetate to be the least thermally stable, both in air and nitrogen, and 1-ethyl-3-methylimidazolium dicyanamide to be the most thermally stable. Dynamic differential scanning calorimetry reveals the formulations comprising DGEBA and ionic liquid where it was revealed that the lowest and highest temperature for the onset of reaction were observed for formulations with 1-ethyl-3-methylimidazolium acetate and 1-ethyl-3-methylimidazolium dicyanamide respectively. 1-Ethyl-3-methylimidazolium acetate was shown, via nuclear magnetic resonance (NMR) spectroscopy and residual gas analysis, to degrade at 150 °C to yield dealkylated products including methyl acetate and ethyl acetate as well as 1-methylimidazole and 1-ethylimidazole. The dealkylated imidazole ring is proposed as a route for initiation of the epoxy ring. Adduct formation between 1-ethyl-3-methylimidazoloium acetate and benzaldehyde at room temperature was observed leading to the proposal of the generation of a carbene species as a route for initiation of the epoxy ring in formulations with the acetate anion. NMR analysis of formulations comprising 1-ethyl-3-methylimidazolium thiocyanate and epoxy are believed, at room temperature, to initiate via reaction of the thiocyanate anion with the epoxy ring. At elevated temperatures, it is proposed that a second, competing reaction, involving deprotonation of the imidazolium ring, also becomes active. The three proposed reaction pathways, namely the carbene route, the imidazole route, and the counter-ion route, are all proposed to occur when an ionic liquid is used to initiate an epoxy resin.