Carbon Bond Formation Research Articles

Rhodium-Catalyzed Hydrocarboxylation: Mechanistic Analysis Reveals Unusual Transition State for Carbon–Carbon Bond Formation

The mechanism of rhodium-COD-catalyzed hydrocarboxylation of styrene derivatives and α,β-unsaturated carbonyl compounds with CO2 has been investigated using density functional theory (PBE-D2/IEFPCM). The calculations support a catalytic cycle as originally proposed by Mikami and co-workers including β-hydride elimination, insertion of the unsaturated substrate into a rhodium–hydride bond, and subsequent carboxylation with CO2. The CO2 insertion step is found to be rate limiting. The calculations reveal two interesting aspects. First, during C–CO2 bond formation, the CO2 molecule interacts with neither the rhodium complex nor the organozinc additive. This appears to be in contrast to other CO2 insertion reactions, where CO2–metal interactions have been predicted. Second, the substrates show an unusual coordination mode during CO2 insertion, with the nucleophilic carbon positioned up to 3.6 A away from rhodium. In order to understand the experimentally observed substrate preferences, we have analyzed a set ...

Catalyst-Directed Guidance of Sulfur-Substituted Enediolates to Stereoselective Carbon-Carbon Bond Formation with Aldehydes.

A highly chemo-, regio-, and stereoselective glycolate aldol reaction of sulfur-substituted enediolates with aldehydes was developed by employing a l-cyclohexylglycine-derived chiral iminophosphorane as a catalyst. The key for establishing this protocol is the distinct ability of the iminophosphorane catalyst to precisely direct the equilibrium mixture of the enediolates toward the intermolecular carbon-carbon bond formation with simultaneous yet rigorous control of relative and absolute stereochemistry. The critical importance of the cyclohexyl substituents on the catalyst backbone in dictating the reaction pathway and the stereochemical outcome was elucidated through an extensive quantum analysis by density functional theory calculations.

Unraveling the Role of a Flexible Tetradentate Ligand in the Aerobic Oxidative Carbon–Carbon Bond Formation with Palladium Complexes: A Computational Mechanistic Study

Mechanistic details of the aerobic oxidative coupling of methyl groups by a novel (MeL)PdII(Me)2 complex with the tetradentate ligand, MeL = N, N-dimethyl-2,11-diaza[3.3](2,6)pyridinophane, has been explored by density functional theory calculations. The calculated mechanism sheds light on the role of this ligand's flexibility in several stages of the reaction, especially as the oxidation state of the Pd changes. Ligand flexibility leads to diverse axial coordination modes, and it controls the availability of electrons by modulating the energies of high-lying molecular orbitals, particularly those with major d z2 character. Solvent molecules, particularly water, appear essential in the aerobic oxidation of PdII by lowering the energy of the oxygen molecule's unoccupied molecular orbital and stabilizing the PdX-O2 complex. Ligand flexibility and solvent coordination to oxygen are essential to the required spin-crossover for the transformation of high-valent PdX-O2 complexes. A methyl cation pathway has been predicted by our calculations in transmetalation between PdII and PdIV intermediates to be preferred over methyl radical or methyl anion pathways. Combining an axial and equatorial methyl group is preferred in the reductive elimination pathway where roles are played by the ligand's flexibility and the fluxionality of trimethyl groups.

Methylation of imidazopyrazine, imidazoquinoxaline, and pyrazoloquinoxaline through Suzuki–Miyaura cross coupling

The Suzuki–Miyaura cross coupling is a versatile and powerful reaction for carbon–carbon bond formation which nevertheless requires optimization of conditions. While the coupling of arylboron derivatives with aryl or alkenyl halides has been widely explored, alkylation has attracted less attention. We describe herein the methylation of bromo derivatives of imidazopyrazine, imidazoquinoxaline, and pyrazoloquinoxaline having biologically interesting structures. As the challenging Suzuki–Miyaura reaction is highly substratedependent, the choices of the base, solvent, and additive are also discussed.

Solvent-determined mechanistic pathways in zeolite-H-BEA-catalysed phenol alkylation

Alkylation of phenolics is of great importance in synthetic chemistry and the valorization of lignocellulosic-biomass-derived streams. Here, we unravel how alkylating reactants and solvents significantly alter the reaction pathways of zeolite-catalysed alkylation of phenol in the liquid phase. The carbenium ion formed from the dehydration of cyclohexanol or from the adsorption and protonation of cyclohexene acts as the electrophile, inducing carbon–carbon bond formation. Cyclohexanol at Bronsted acid sites (BAS) forms hydrogen-bonded monomers and protonated dimers in apolar solvents. The dimer appears to generate a much lower concentration of carbenium ions compared with the monomer. Higher alkylation rates in apolar solvents than in water are caused by the energetically more-favourable carbenium ion formation from either alcohol or olefin on non-hydrated zeolite BAS than on hydronium ions produced by BAS in pores filled with water. Zeolite-catalysed alkylations of phenolic compounds offer unique possibilities for the valorization of renewable aromatics into substituted arenes. Now, a mechanistic study reveals that the course of the reaction can be dramatically altered by changing the polarity of the solvent, which affects the nature of surface species and the pathway for the generation of the alkylating electrophile.

Post Polyketide Synthase Carbon-Carbon Bond Formation in Type-II PKS-Derived Natural Products from Streptomyces venezuelae.

Polyketide synthase (PKS) derived natural products are biosynthesized by head-to-tail addition of acetate and malonate extender units resulting in linear extended-polyketide chains. Despite the well-documented structural diversity associated with PKS-derived natural products, C-C chain branching deviating from the usual linear pattern is relatively rare. Herein, type-II PKS angucyclic natural products containing a hemiaminal functionality were identified and proposed as the parent of a series of C-C-branched analogues. These C-C linked acetate or pyruvate branching units were located at the α-positions on the extended polyketide chains of jadomycins incorporating 3- and 4-aminomethylbenzoic acids. Labeling studies utilizing [1-13C]-d-glucose provided mechanistic evidence that the C-C bond formation occurred as a result of a previously unidentified post-PKS processing, additional to the enzymes encoded within the biosynthetic gene cluster. Selected compounds were evaluated in cytotoxic or antimicrobial assays.

Controlling the layer localization of gapless states in bilayer graphene with a gate voltage

Experiments in gated bilayer graphene with stacking domain walls present topological gapless states protected by no-valley mixing. Here we research these states under gate voltages using atomistic models, which allow us to elucidate their origin. We find that the gate potential controls the layer localization of the two states, which switches non-trivially between layers depending on the applied gate voltage magnitude. We also show how these bilayer gapless states arise from bands of single-layer graphene by analyzing the formation of carbon bonds between layers. Based on this analysis we provide a model Hamiltonian with analytical solutions, which explains the layer localization as a function of the ratio between the applied potential and interlayer hopping. Our results open a route for the manipulation of gapless states in electronic devices, analogous to the proposed writing and reading memories in topological insulators.

Crystal structure of cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces cerevisiae.

Thiolases are vital enzymes which participate in both degradative and biosynthetic pathways. Biosynthetic thiolases catalyze carbon-carbon bond formation by a Claisen condensation reaction. The cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces cerevisiae, ERG10, catalyses carbon-carbon bond formation in the mevalonate pathway. The structure of a S. cerevisiae biosynthetic thiolase has not previously been reported. Here, crystal structures of apo ERG10 and its Cys91Ala variant were solved at resolutions of 2.2 and 1.95 Å, respectively. The structure determined shows that ERG10 shares the characteristic thiolase superfamily fold, with a similar active-site architecture to those of type II thiolases and a similar binding pocket, apart from Ala159 at the entrance to the pantetheine-binding cavity, which appears to be a determinant of the poor binding ability of the substrate. Moreover, comparative binding-pocket analysis of molecule B in the asymmetric unit of the apo structure with that of the CoA-bound complex of human mitochondrial acetoacetyl-CoA thiolase indicates the canonical binding mode of CoA. Furthermore, the steric hindrance revealed in a structural comparison of molecule A with the CoA-bound form raise the possibility of conformational changes that are associated with substrate binding.

Palladium functionalized phosphinite polyethyleneimine grafted magnetic silica nanoparticles as an efficient catalyst for the synthesis of isoquinolino[1,2-b]quinazolin-8-ones

Novel 5-methyl-8H-isoquinolino[1,2-b]quinazolin-8-one derivatives are synthesized using a reusable immobilized palladium catalyzed intramolecular carbon–carbon bond formation.

Fluoride Ion-Mediated Electrochemical Synthesis of β, β, β-Trifluorolactic Aldehyde Equivalent and CF3-Containing 1,3-Oxathiolanes

Fluoride ion-mediated anodic methoxylation of 1,1,1-trifluoropropyl-3-(phenylthio)propan-2-ol was successfully carried out to provide the corresponding α-methoxylated product, β,β,β-trifluorolactic aldehyde equivalent, which was demonstrated to be a useful CF3-containing building block for diastereoselective carbon–carbon bond formation. The fluoride ion-mediatory system was also successfully applied to anodic intramolecular alkoxylation of 1-(benzylthio)-3,3,3-trifluoro-propan-2-ol and its derivatives to afford the corresponding CF3-containing 1,3-oxathiolanes as a stereoisomeric mixture in good yields. This is the first successful example of anodic intramolecular alkoxylation of saturated organo sulfur compounds.

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes.

1,1-Difluoro-1-alkenes bearing a biaryl-2-yl group effectively underwent site-selective intramolecular iodoarylation by the appropriate cationic iodine species. Iodoarylation of 2-(2-aryl-3,3-difluoroallyl)biaryls proceeded via regioselective carbon–carbon bond formation at the carbon atoms in β-position to the fluorine substituents, thereby constructing dibenzo-fused six-membered carbocycles bearing a difluoroiodomethyl group. In contrast, 2-(3,3-difluoroallyl)biaryls underwent a similar cyclization at the α-carbon atoms to afford ring-difluorinated seven-membered carbocycles.

The introduction of the Barbier reaction into polymer chemistry

The Barbier reaction, a widely utilized reaction for carbon–carbon bond formation, has played important roles in modern organic chemistry for more than a century. Here, we show its successful introduction to polymer chemistry. Through one-pot Barbier polyaddition (both A2+B2 type and AB type) of monomers containing an organic halide and a benzoyl group, a series of phenylmethanol group containing polymers, including polymonophenylmethanol (PMPM), polydiphenylmethanol (PDPM), and polytriphenylmethanol (PTPM), have been synthesized. Para-PTPM exhibits interesting aggregation-induced emission, tunable thermo-responsive over a wide temperature range, sensory, luminescence enhancement of fluorescent dye in solid-state and processing properties. This significantly expands the libraries of monomer and polymer, and opens up an avenue for the design and application of functional polymer materials.

Synthesis and Characterization of Hybrid Mg(OH)2 and CeCO3OH Composite with Improved Activity Towards Henry Reaction

AbstractA new approach was developed for carbon–carbon bond formation via Henry reaction using a mixture of Mg(OH)2 and CeCO3OH (MgCe‐HDC). The MgCe‐HDC was synthesized using a co‐precipitation method and was characterized by SEM, XRD, FTIR, TGA‐DTA, and AFM. The effects of temperature, solvent, and the amount of catalyst were investigated to find the optimum reaction conditions. The highest yield of nitroaldol product, 92 %, was achieved over the reusable solid base catalyst in solvent‐free conditions at 20 °C.

Visible light-induced reduction properties of diphenylviologen with water-soluble porphyrin

Molecular conversion reaction system containing a dye and a biocatalyst catalyzing a reaction of a carbon–carbon bond formation from CO2 as a feedstock were constructed. For example, NADP-malic enzyme (ME, EC1.1.1.40) catalyzes the reaction of introducing CO2 as a carboxy group to pyruvate (C3 compound) to form malate (C4 compound) via oxaloacetate in the presence of natural co-enzyme NADPH. In a recent study, visible light-induced oxaloacetate production from pyruvate and CO2 with the system consisting an electron donor, a photosensitizer, diphenylviologen (PV2+) derivative as an electron mediator and ME was reported. However, the visible light-induced reduction properties of PV2+ with water-soluble Zn porphyrin have not been clarified. In this study, chemical and photo-redox properties of PV2+ were studied. In addition, to produce malate, CO2 saturated reaction solution containing triethanolamine, tetraphenylporphine tetrasulfonate (H2TPPS), pyruvate, PV2+ and ME in the presence of Mg2+, co-factor for ME was irradiated with visible-light, the oxaloacetate and malate were produced.

Synthesis of Benzamide Derivatives by the Reaction of Arenes and Isocyanides through a C–H Bond Activation Strategy

A carbon–carbon bond formation reaction between isocyanides and benzene derivatives is reported. In contrast to traditional cross-coupling reactions, which require aryl halides or pseudohalides, we use a palladium catalyst to generate the aryl–palladium through C–H bond activation of arenes. This method offers an attractive approach to a range of benzamides from readily accessible benzene derivatives.

It Is Not Just Up to the Substrate: Palladium(0) Cyclizes Nazarov Substrates through Intramolecular Allylic Alkylation

Plausible mechanisms of Pd0-catalyzed cyclization of diketoesters were modeled using density functional theory calculations. Comparison of the reaction mechanisms of uncatalyzed and Pd0-catalyzed cyclizations revealed the vital role of the Pd0 catalyst. Both reactions favor a stepwise mechanism involving a proton transfer followed by carbon–carbon bond formation over either the reverse order or a concerted mechanism. The key step for the Pd0-catalyzed reaction is the formation of a relatively stable intermediate, an η3-allyl PdII complex, in the lowest energy pathway. Our proposed mechanism is consistent with a Pd0-catalyzed intramolecular allylic alkylation reaction, previously referred to as “Nazarov-type” reactions. It is worth noting that, in contrast to many allylic alkylations, the Pd0-catalyzed cyclization does not require any additional reagents or an activated leaving group to form an η3-allyl PdII complex; thus, the α-hydroxycyclopentenone is produced from diketoesters with no waste. Furthermore...

Carbon-Carbon Bond Formation by Reaction of Rhodium Azavinylcarbenes with Secondary Amides: Access to Indigo Analogues from Isatins.

A novel protocol for the synthesis of unsymmetrical indigo-like (E)-α-amino enaminones by rhodium-catalyzed transformations of isatins with 1-tosyl-1,2,3-triazoles has been developed. A plausible reaction mechanism is proposed to account for the formation of structurally important unsymmetrical indigo analogues, which represents a new strategy for C-C bond formation based on the transformations of secondary amides and rhodium azavinylcarbenes.

A Highly Stereoselective and Efficient Catalytic Approach for the Synthesis of trans‐Stilbene–Arenes as π‐Conjugated Materials

The potential expansion of the variety of catalytic methods for carbon–carbon bond formation is explored in many research centers all over the world. In this work, we describe very precise and controlled catalytic transformations as useful tools for the synthesis of new trans‐π‐conjugated molecular organic compounds. The combination of Suzuki–Miyaura coupling and cross‐metathesis reactions is established as a simple and efficient method for the design of new (E)‐stilbenes in the presence of well‐defined transition‐metal catalysts at 0.0001–1 % loadings. All of the desired products are isolated in good‐to‐excellent yields (up to 96 % isolated yield) with high purity.

Effect of concurrent electron irradiation on the structure of deposited carbon films

Carbon films 110–180 nm thick are fabricated on nickel substrates by the ion sputtering of graphite with simultaneous electron irradiation and subsequent ion irradiation. Irradiation leads to the formation of bonds in the films in various proportions due to the sp and sp 3 hybridization of orbitals (sp-and sp 3-bonds). Ion irradiation induces, to a greater extent, the formation of sp bonds, while concurrent electron irradiation increases the portion of sp 3 bonds. Electron and ion irradiation increases the film microhardness which reaches a value of 12 GPa. A model of the kinetics of creating carbon allotropes in a deposited film is proposed, which is based on the competition between the formation and breakage of carbon bonds during hybridization of different types. Electron and ion irradiation influence the probabilities of the formation and breakage of carbon bonds in the deposited film. The model provides a qualitative interpretation of the observed content ratios of carbon phases in the deposited film.

Nitrogen–Carbon Bond Formation by Reactions of a Titanium–Potassium Dinitrogen Complex with Carbon Dioxide, tert‐Butyl Isocyanate, and Phenylallene

AbstractNitrogen–carbon bond‐forming reactions at coordinated dinitrogen in a bifunctional titanium–potassium system are reported. A titanium atrane complex with a tris(aryloxide)methyl ligand (1) was treated with two equivalents of potassium naphthalenide under N2 atmosphere to generate a bifunctional complex (2) in which N2 binds end‐on to two titanium centers and side‐on to three potassium cations. Dinitrogen complex 2 reacted with carbon dioxide, tert‐butyl isocyanate, and phenylallene, forming nitrogen–carbon bonds and affording diverse N‐functionalized products. The reaction of 2 with CO2 followed by addition of Me3SiCl resulted in the formation of the starting complex 1 with concomitant release of silylated carboxyl hydrazines while the reaction with two equivalents of tert‐butyl isocyanate proceeded by insertion into the Ti−N bonds. Treatment of 2 with phenylallene afforded vinyl‐substituted hydrazido complexes.