Reactions Of Carbanions Research Articles

Rh-Catalyzed Coupling Reactions of Fluoroalkyl N-Sulfonylhydrazones with Azides Leading to α-Trifluoroethylated Imines.

Herein we describe the pioneering Rh-catalyzed coupling reactions of a fluoroalkyl carbene with azides to access α-trifluoroethylated imines, where fluoroalkyl N-sulfonylhydrazones are used as fluoroalkyl diazo surrogates. Remarkably, using TMSN3 as the N source, two C-N bond formation products were obtained. Furthermore, the α-trifluoroethylated imine products could be easily reduced to the corresponding N-trifluoroethylated anilines. Experimental results and theoretical calculations justify a stepwise reaction pathway involving the formation of rhodium carbene, the addition of HN3, and C═N bond formation.

Activation of Ge-H and Sn-H Bonds with N-Heterocyclic Carbenes and a Cyclic (Alkyl)(amino)carbene.

A study of the reactivity of several N-heterocyclic carbenes (NHCs) and the cyclic (alkyl)(amino)carbene 1-(2,6-di-iso-propylphenyl)-3,3,5,5-tetramethyl-pyrrolidin-2-ylidene (cAACMe ) with the group 14 hydrides GeH2 Mes2 and SnH2 Me2 (Me=CH3 , Mes=1,3,5-(CH3 )3 C6 H2 ) is presented. The reaction of GeH2 Mes2 with cAACMe led to the insertion of cAACMe into one Ge-H bond to give cAACMe H-GeHMes2 (1). If 1,3,4,5-tetramethyl-imidazolin-2-ylidene (Me2 ImMe ) was used as the carbene, NHC-mediated dehydrogenative coupling occurred, which led to the NHC-stabilized germylene Me2 ImMe ⋅GeMes2 (2). The reaction of SnH2 Me2 with cAACMe also afforded the insertion product cAACMe H-SnHMe2 (3), and reaction of two equivalents Me2 ImMe with SnH2 Me2 gave the NHC-stabilized stannylene Me2 ImMe ⋅SnMe2 (4). If the sterically more demanding NHCs Me2 ImMe , 1,3-di-isopropyl-4,5-dimethyl-imidazolin-2-ylidene (iPr2 ImMe ) and 1,3-bis-(2,6-di-isopropylphenyl)-imidazolin-2-ylidene (Dipp2 Im) were employed, selective formation of cyclic oligomers (SnMe2 )n (5; n=5-8) in high yield was observed. These cyclic oligomers were also obtained from the controlled decomposition of cAACMe H-SnHMe2 (3).

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

Chemical grafting of graphene onto carbon fiber to produce composites with improved interfacial properties via sizing process: A step closer to industrial production

The previous results indicated that the bonding strength between graphene and carbon fiber (CF) has a greater impact on the reinforcement efficiency. And chemical bonding can provide the maximum bonding force between graphene and CF, which usually requires a series of complicated processes and a long preparation time. In this research, we have established a direct and efficient method to manufacture Graphene/CF hierarchical reinforcement based on chemical bonding. The Graphene/CF hierarchical reinforcement was prepared by the means of the rapid insertion and addition reaction of diaryl carbene. FTIR, Raman, XPS, XRD confirmed the structure of graphene and CF. Graphene-modified multi-scale composites exhibit excellent comprehensive properties, including ILSS (97.2 MPa), flexural strength (2043 MPa) and Tg (240 °C), which are increased by 23.2%, 34.4%, and 13 °C, respectively. This protocol was considered to provide an alternative strategy for the rapid and large-scale manufacturing of graphene/CF hierarchical reinforced materials based on covalent bonds.

Asymmetric Three-Component Reaction of Enynal with Alcohol and Imine as An Expeditious Track to Afford Chiral α-Furyl-β-amino Carboxylate Derivatives

Herein, we report an achiral dirhodium complex and chiral phosphoric acid cooperatively catalyzed asymmetric three-component reaction of enynal with alcohol and imine, affording chiral α-furyl-β-amino carboxylates in good to high yields with generally excellent stereoselectivity. The successful introduction of enynal as a carbene precursor in this reaction provides an expeditious track to prepare complex furan derivatives with adjacent quaternary and tertiary stereocenters. The starting materials are stable and readily available, and the method features 100% atom economy with high bond-formation efficiency. This is a highly enantioselective gem-difunctionalization reaction of metal carbene generated in situ from enynal. These generated chiral products could be smoothly converted to polycyclic frameworks and drug-conjugated derivatives through different cycloaddition reactions.

Stereocontrolled acyclic diene metathesis polymerization.

The cis/trans geometry of olefins is known to dramatically influence the thermal and mechanical properties of polyalkenamers. Yet, polymerization methods that efficiently control this parameter are scarce. Here we report the development of a stereoretentive acyclic diene metathesis polymerization that uses the reactivity of dithiolate Ru carbenes combined with cis monomers. These Ru catalysts exhibit exquisite retention of the cis geometry and tolerate many polar functional groups, enabling the synthesis of all-cis polyesters, polycarbonates, polyethers and polysulfites. The stereoretentive acyclic diene metathesis polymerization is also characterized by low catalyst loadings and tolerance towards trans impurities in the monomer batch, which should facilitate large-scale implementation. Modulation of the reaction temperature and time leads to an erosion of stereoretention, permitting a stereocontrolled synthesis of polyalkenamers with predictable cis:trans ratios. The impact of the stereochemistry of the repeating alkenes on the thermal properties is clearly demonstrated through differential scanning calorimetry and thermogravimetric analysis.

Synthesis of Linear and Cyclic Discrete Oligomers with Defined Sequences via Efficient Anionic Coupling Reaction

We hereby report a new strategy to prepare sequence-defined discrete oligomers with uniform molecular weight through carbanionic addition and coupling reactions using specific monomers possessing 1,1-diphenylethylene (DPE) and tert-butyldimethylsilyloxy (TBS) moieties. The strategy allows the molecular weight growth by iterative attaching of the sec-butyllithium (s-BuLi) activated monomer or dimer unit to the halomethyl end-group, released from deprotection of TBS, of the proceeding oligomer starting from a dichloromethyl core. A series of linear discrete oligomers with alternating and ABCD/ACBD sequences are synthesized. These linear sequence-defined oligomers are subsequently modified with double vinyl groups and cyclized through ring-closing metathesis (RCM) reaction into corresponding sequence-defined macrocycles. The molecular structures of the linear and cyclic oligomers are analyzed by using size exclusion chromatography (SEC), nuclear magnetic resonance (NMR), and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The features of the present approach are the presynthesized monomers or dimers with specific functionalities, the efficient carbanionic reactions, as well as the easy separation of the products due to the increasing difference between the molecular weights of the monomer/dimer and the products. More interestingly, sequence and topology effects were observed on Förster resonance energy transfer (FRET) measurements using naphthalene (donor) and pyrene (acceptor) functionalized linear and cyclic ABCD/ACBD oligomers having identical molecular weights and compositions for the two sequences.

Structures and Chemical Rearrangements of Benzoate Derivatives Following Gas Phase Decarboxylation.

Decarboxylation of carboxylate ions in the gas phase provides a useful window into the chemistry displayed by these reactive carbanion intermediates. Here, we explore the species generated by decarboxylation of two benzoate derivatives: 2-formylbenzoate (2FBA) and 2-benzoylbenzoate (2BBA). The nascent product anions are transferred to a cryogenic ion trap where they are cooled to ∼15 K and analyzed by their pattern of vibrational bands obtained with IR photodissociation spectroscopy of weakly bound H2 molecules. The structures of the quenched species are then determined by comparison of these spectra with those predicted by electronic structure calculations for local minima on the potential energy surface. The 2-phenide carbanion generated by decarboxylation of 2FBA occurs in two isomeric forms that differ in the orientation of the formyl group, both of which yield a very large (∼110 cm-1) redshift in the stretching frequency of the H2 molecule attached to the anionic carbon center. Although calculated to be a local minimum, the analogous 2-phenide species could not be isolated upon decarboxylation of 2BBA. Rather, the anionic product adopts a ring-closed structure, indicating efficient nucleophilic attack on the pendant phenyl group by the nascent phenide. The barrier for ring closing is evaluated with electronic structure calculations.

Synthesis, structure and reactivity of a boron-containing spirocycle carbanion

The crystal structure, electronic characteristic, as well as the formation process, and nucleophilic reactivity of an unexpected boron-containing carbanion are presented. Its structure consists of a discrete cation and a spirocycle structure, in which the sp 3 hybrid C7 atom connects the mesityl substituted oxaborole unit and the puckered anthracene moiety. • A novel boron-containing carbanion with distinct structural characteristics was synthesized, which was composed of a discrete [K(cryptand)] + ion and a spirocycle anion. • The formation and electronic structure of carbanion were explored through DFT calculations. • The nucleophilic reactivity of carbanion with some chlorosilane or halogenated alkanes in THF solution was evaluated. Carbanion ( 2 ) was synthesized by the deprotonation strategy through treatment of (2-(anthracen-9-yl)phenyl)(hydroxy)(mesityl)borane ( 1-H ) with KN(SiMe 3 ) 2 in the presence of [2,2,2]-cryptand in tetrahydrofuran (THF) solution followed by crystallization of the crude product from cooled THF. Its crystal structure and electronic properties are presented, as well as the formation process and nucleophilic reactivity with chlorosilane or halogenated alkanes.

Enantioselective Copper‐Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides

AbstractCarbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O‐heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst‐controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper‐catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote‐stereocontrol strategy.

Enantioselective Copper-Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides.

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O-heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst-controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper-catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom-economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote-stereocontrol strategy.

Dark and Light Reactions of Carbenes─Merging Carbene Transfer Reactions with N-Heterocyclic Carbene Catalysis for the Synthesis of Hydroxamic Acid Esters

Herein, we report visible light and N-heterocyclic carbene (NHC) jointly promoted multicomponent carbene transfer reactions. Under the optimized reaction conditions, two kinds of important hydroxamic acid esters were obtained in good yields depending on the reaction media used. The key to this success was driven by the blue light-promoted generation of free carbene species and the fast in situ formation of hydroxamic acid under NHC-catalyzed conditions. The mild reaction conditions, excellent functional group tolerance, useful synthetic transformations, and successful modification of natural products and drug molecules proved the utility and practicality of this method.

New Carbenes and Cyclic Allenes Energetically Comparable to Experimentally Known 1-Azulenylcarbene

1-Azulenylcarbene (18; 0 kJ mol–1) is experimentally known as the key reactive intermediate for the rearrangement reactions of aryl carbenes in the laboratory. Here, using coupled-cluster methods up to the fc-CCSD(T)/cc-pVTZ//fc-CCSD(T)/cc-pVDZ level, thirteen new carbenes and one new cyclic allene are theoretically identified within the C11H8 elemental composition that either energetically lie below or very close to 18. While the cyclic allene, bicyclo[5.4.0]undeca-2,3,5,7,9,11-hexene (1; −166 kJ mol–1), is the experimentally known lowest energy isomer, three other cyclic allenes, bicyclo[5.4.0]undeca-1,2,4,6,8,10-hexene (2; −100 kJ mol–1), bicyclo[5.4.0]undeca-1,3,4,6,8,10-hexene (3; −97 kJ mol–1), and bicyclo[6.3.0]undeca-1,2,4,6,8,10-hexene (13; −42 kJ mol–1), demand new experimental studies. In total, thirty-one isomers are studied in this work (within −166 to +15 kJ mol–1 from 18) and all are found to be polar (μ ≠ 0). Among these, 1H-benzo[7]annulen-1-ylidene (17; −4 kJ mol–1; μ = 5.24 D), bicyclo[5.4.0]undeca-2,4,6,8,11-pentaene-10-ylidene (24; 13 kJ mol–1; μ = 7.59 D), 5-methylene-naphthalen-1-ylidene (26; 15 kJ mol–1; μ = 5.32 D), 6-methylene-naphthalen-2-ylidene (27; −43 kJ mol–1; μ = 6.60 D), and 8-methylene-naphthalen-2-ylidene (28; −39 kJ mol–1; μ = 5.55 D) are competitively polar compared to 18 (μ = 5.39 D). Therefore, these carbene molecules are potential targets for rotational spectroscopists and radioastronomers. Considering the importance of naphthyl and azulenylcarbenes in reactive intermediate chemistry, mechanisms of different rearrangement reactions and plausible formation pathways of some of these new carbenes are studied in this work using density functional theory.

Carbene reactivity from alkyl and aryl aldehydes.

Carbenes are highly enabling reactive intermediates that facilitate a diverse range of otherwise inaccessible chemistry, including small-ring formation and insertion into strong σ bonds. To access such valuable reactivity, reagents with high entropic or enthalpic driving forces are often used, including explosive (diazo) or unstable (gem-dihalo) compounds. Here, we report that common aldehydes are readily converted (via stable α-acyloxy halide intermediates) to electronically diverse (donor or neutral) carbenes to facilitate >10 reaction classes. This strategy enables safe reactivity of nonstabilized carbenes from alkyl, aryl, and formyl aldehydes via zinc carbenoids. Earth-abundant metal salts [iron(II) chloride (FeCl2), cobalt(II) chloride (CoCl2), copper(I) chloride (CuCl)] are effective catalysts for these chemoselective carbene additions to σ and π bonds.

Safe, selective, and scalable carbenes.

The synthesis of reactive carbene intermediates is made simpler and safer.

Bonding Nature of "Ionic Carbenes" in [M3(μ3-CH2)]-Containing Compounds: The Covalent Interaction.

While a series of trinuclear rare-earth metal methylene (divalent >CH2) complexes with the so-called "ionic carbene" have been known for decades, the nature of metal-carbene interactions in this class of compounds remains elusive. Herein, a quantum chemical investigation has been performed to reveal the bonding nature in typical trimetallic "ionic carbene" species with the [M3(μ3-CH2)] (M = Sc, Y, La, and Ac) cluster core. Through various chemical bonding analyses, we have demonstrated that there exists a non-negligible covalent interaction between μ3-CH2 and M3 moieties, and the chemical bonding can be accounted for with two three-center two-electron (3c-2e) bonds. The chemical bonding analyses reveal that the metal d-electron configuration plays an important role in stabilizing various μ3-coordinated carbene complexes. The late transition metals do not favor such a μ3-coordination geometry, thus explaining why ionic carbene complexes are usually found for rare-earth and early transition metals. A series of ionic carbene complexes with early transition metals, lanthanides, and actinides are predicted to be stable as well. These reactive ionic carbene complexes may have characteristic properties for organic synthesis and catalysis.

Controlled Alternating Metathesis Copolymerization of Terminal Alkynes.

Terminal alkynes display high reactivity toward Ru-carbene metathesis catalysts. However, the formation of a less reactive bulky carbene hinders their homopolymerization. Simultaneously, the higher reactivity of alkynes does not allow efficient cross propagation with sterically less-hindered cycloalkene monomers, resulting in inefficient copolymerization. Nonetheless, terminal alkynes undergo rapid cross-metathesis with vinyl ethers. Therefore, an efficient cross propagation can be achieved with terminal alkynes and cyclic enol ether monomers. Here, we show that terminal alkyne derivatives can be copolymerized in an alternating fashion with 2,3-dihydrofuran using Grubbs' third generation catalyst (G3). A linear relationship of the number-average molecular weight versus monomer to initiator ratio and block copolymer synthesis confirmed a controlled copolymerization. The SEC and NMR analyses of the synthesized copolymers confirmed the excellent control over molecular weight and exclusive alternating nature of the copolymer. The regioselective chain transfer of G3 to vinyl ether and the high reactivity of the Fischer-type Ru carbene toward terminal alkynes was also exploited for polymer conjugation. Finally, the presence of an acid labile backbone functionality in the synthesized alternating copolymers allowed complete degradation of the copolymer within a short time interval which was confirmed by SEC analyses.

Therapeutic N-heterocyclic carbenes: an interview with Alejandro Bugarin.

DrBugarin is currently an Associate Professor of Chemistry and Physics at Florida Gulf Coast University. He has published more than 50 peer-reviewed publications (h-index = 18). His research group is developing newmethodology to improve or reveal novel reactivity of triazenes, N-Heterocyclic carbenes, heterobimetallic catalysts, and other versatile molecules. In addition, he recently joined research efforts to build on theisolation, characterization, and biological evaluation of natural products.

Direct Observation of the Dynamics of Ylide Solvation by Hydrogen-bond Donors Using Time-Resolved Infrared Spectroscopy.

The photoexcitation of α-diazocarbonyl compounds produces singlet carbene intermediates that react with nucleophilic solvent molecules to form ylides. The zwitterionic nature of these newly formed ylides induces rapid changes in their interactions with the surrounding solvent. Here, ultrafast time-resolved infrared absorption spectroscopy is used to study the ylide-forming reactions of singlet carbene intermediates from the 270 nm photoexcitation of ethyl diazoacetate in various solvents and the changes in the subsequent ylide–solvent interactions. The results provide direct spectroscopic observation of the competition between ylide formation and C–H insertion in reactions of the singlet carbene with nucleophilic solvent molecules. We further report the specific solvation dynamics of the tetrahydrofuran (THF)-derived ylide (with a characteristic IR absorption band at 1636 cm–1) by various hydrogen-bond donors and the coordination by lithium cations. Hydrogen-bonded ylide bands shift to a lower wavenumber by −19 cm–1 for interactions with ethanol, −14 cm–1 for chloroform, −10 cm–1 for dichloromethane, −9 cm–1 for acetonitrile or cyclohexane, and −16 cm–1 for Li+ coordination, allowing the time evolution of the ylide–solvent interactions to be tracked. The hydrogen-bonded ylide bands grow with rate coefficients that are close to the diffusional limit. We further characterize the specific interactions of ethanol with the THF-derived ylide using quantum chemical (MP2) calculations and DFT-based atom-centered density matrix propagation trajectories, which show preferential coordination to the α-carbonyl group. This coordination alters the hybridization character of the ylidic carbon atom, with the greatest change toward sp2 character found for lithium-ion coordination.

Gas-Phase Reactivity of Phenylcarbyne Anions.

Gas-phase reactivities of the phenylcarbyne anion and its four derivatives were studied using a linear quadrupole ion trap mass spectrometer. The phenylcarbyne anions were calculated to have a triplet ground state (singlet-triplet splittings of 4-9 kcal mol-1), with the exception of the 4-cyanophenylcarbyne anion that has a singlet ground state (singlet-triplet splitting of -1.9 kcal mol-1). Only the phenylcarbyne anions with a triplet ground state react with acetone and dimethyl disulfide via radical mechanisms. On the other hand, only the phenylcarbyne anion with a singlet ground state abstracts H2O and H2C═C═O from acetic acid via electrophilic addition of the reagents to the anion. Finally, two hydroxy-substituted phenylcarbyne anions (with triplet ground states) partially tautomerize with the assistance of reagent molecules to the more stable distonic phenylcarbene anions. This occurs via abstraction of a proton from the reagent by the phenylcarbyne anion to generate a neutral (triplet) phenylcarbene and a reagent anion, which is followed by proton abstraction from the hydroxyl group of the neutral phenylcarbene by the reagent anion to generate the distonic phenylcarbene anion in an excited triplet state. Experiments performed on deuterated hydroxy-substituted phenylcarbyne anions verified the mechanism. The reactivities of the distonic phenylcarbene anions were found to be quite different from those of the phenylcarbyne anions. For example, they were found to abstract CH2 from acetonitrile, which is initiated by C-H insertion─typical singlet carbene reactivity.