Carbon-carbon Coupling Reactions Research Articles

The Progress of Reductive Coupling Reaction by Iron Catalysis.

The transition metal catalyzed coupling reaction has revolutionized the strategies for forging the carbon-carbon bonds. In contrast to traditional cross-coupling methods using pre-prepared nucleophilic organometallic reagents, reductive coupling reactions for the C-C bonds formation provide some advantages. Because both coupling partners are reduced in the final products using a stoichiometric amount of a reductant, this approach not only avoids the need to use sensitive organometallic species, but also provides an orthogonal and complementary access to classical coupling reaction. Notably, the reductive coupling reactions feature readily available fragments, promote good step economy, exhibit high functional group tolerance and unique chemoselectivity, which have propelled their increasingly popular in the organic synthesis. In recent years, due to the low price, minimal toxicity, and environmentally benign character, iron-catalyzed carbon-carbon coupling reactions have garnered significant attention from the organic synthetic chemists and pharmacologists, especially the iron-catalyzed reductive coupling. This review aims to provide an insightful overview of recent advances in iron-catalyzed reductive coupling reactions, and to illustrate their possible reaction mechanisms.

Cascade C-H Activation and Two C-C Bond Forming in Reaction of Azalutetacyclopentadiene with 2-Methylbenzonitriles.

Azametallacyclopentadienes are an important class of metallacycles as the key intermediates in metal-promoted or catalyzed carbon-carbon coupling reaction of nitriles and alkynes. Rare-earth azametallacyclopentadienes have shown various reactivity toward nitriles, depending on the substituents of nitriles. The reaction of azalutetacyclopentadienes toward 2-methylbenzonitriles has been investigated in this work, which selectively affords the fused 7-5-6-membered azalutetacycles as products. Computational studies reveal that the reaction of azalutetacyclopentadienes toward 2-methylbenzonitriles selectively initiates with the remote activation of the benzylic C-H bond by the Lu-N bond, followed by the intramolecular nucleophilic attack from the deprotonated benzylic carbon to form a C-C bond. Subsequently, the high ring strain promoted the generation of the uncoordinated carbanion dissociated from the lutetium center, which then undergoes intramolecular nucleophilic attack toward C=N triple bond to give the final product containing fused 7-5-6-membered azalutetacycle. This work not only achieves highly selective three-step cascade reaction to form a unique class of rare-earth metallacycle, but also provides a new idea for the transformation of unsaturated substrates with C-H bonds that can be activated.

Chemoenzymatic Synthesis of Fluorinated Mycocyclosin Enabled by the Engineered Cytochrome P450-Catalyzed Biaryl Coupling Reaction.

Installing fluorine atoms onto natural products holds great promise for the generation of fluorinated molecules with improved or novel pharmacological properties. The enzymatic oxidative carbon-carbon coupling reaction represents a straightforward strategy for synthesizing biaryl architectures, but the exploration of this method for producing fluorine-substituted derivatives of natural products remains elusive. Here, in this study, we report the protein engineering of cytochrome P450 from Mycobacterium tuberculosis (MtCYP121) for the construction of a series of new-to-nature fluorine-substituted Mycocyclosin derivatives. This protocol takes advantage of a "hybrid" chemoenzymatic procedure consisting of tyrosine phenol lyase-catalyzed fluorotyrosine preparation from commercially available fluorophenols, intermolecular chemical condensation to give cyclodityrosines, and an engineered MtCYP121-catalyzed intramolecular biphenol coupling reaction to complete the strained macrocyclic structure. Computational mechanistic studies reveal that MtCYP121 employs Cpd I to abstract a hydrogen atom from the proximal phenolic hydroxyl group of the substrate to trigger the reaction. Then, conformational change makes the two phenolic hydroxyl groups close enough to undergo intramolecular hydrogen atom transfer with the assistance of a pocket water molecule. The final diradical coupling process completes the intramolecular C-C bond formation. The efficiency of the biaryl coupling reaction was found to be influenced by various fluorine substitutions, primarily due to the presence of distinct binding conformations.

Synthesis, characterization, and XPS study of woolen-like zeolite X-palladium nanoparticles: its application as a suitable catalyst for carbon-carbon coupling reaction

Here, a green methodology for synthesis of powerful catalyst of zeolite X-palladium nanoparticles (Z-X-Pd NPs) is reported. The physicochemical properties of the samples were carried out by X‐ray diffraction (XRD), X-ray photoelectron spectroscopy, Brunauer Emmett Teller and Fourier-transform infrared spectroscopy, transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, scanning electron microscopy mapping images techniques with a clear interpretation of each analysis. From the XRD’s calculation, it can demonstrate the improvement of the crystallinity index (92.99%) and D (22.55%) values of Z-X-Pd NPs sample, compared with zeolite X (Z-X) sample. Z-X-Pd NPs not only did not have impure phases, but also a characteristic grooved-like of structures were disclosed with a good distribution of Pd NPs on the Z-X surface, confirmed by other analysis outputs. Afterward, the Suzuki-Miyaura (S-M) reaction was precisely studied by applying the desired conditions. Under the optimized conditions acid derivatives were efficiently reacted with aryl halides with their various conjugates, resulting in good yields of about 99% (particularly in aryl fluorides).

Highly Selective Acetylene-to-Ethylene Electroreduction Over Cd-Decorated Cu Catalyst with Efficiently Inhibited Carbon-Carbon Coupling.

Electrochemical acetylene reduction (EAR) employing Cu catalysts represents an environmentally friendly and cost-effective method for ethylene production and purification. However, Cu-based catalysts encounter product selectivity issues stemming from carbon-carbon coupling and other side reactions. We explored the use of secondary metals to modify Cu-based catalysts and identified Cd decoration as particular effective. Cd decoration demonstrated a high ethylene Faradaic efficiency (FE) of 98.38 % with well-inhibited carbon-carbon coupling reactions (0.06 % for butadiene FE at -0.5 V versus reversible hydrogen electrode) in a 5 vol % acetylene gas feed. Notably, ethylene selectivity of 99.99 % was achieved in the crude ethylene feed during prolonged stability tests. Theoretical calculations revealed that Cd metal accelerates the water dissociation on neighboring Cu surfaces allowing more H* to participate in the acetylene semi-hydrogenation, while increasing the energy barrier for carbon-carbon coupling, thereby contributing to a high ethylene semi-hydrogenation efficiency and significant inhibition of carbon-carbon coupling. This study provides a paradigm for a deeper understanding of secondary metals in regulating the product selectivity of EAR electrocatalysts.

Efficient heck and Suzuki-Miyaura cross-coupling reactions catalyzed by heterogeneous Pd NPs-decorated porous MOF catalysts under mild conditions

Carbon-carbon coupling reactions are extremely interesting for a variety of applications, including pharmaceuticals and biologically active compounds. In this study, we investigated the utilization of functionalized MIL-101 porous MOF for stabilizing palladium nanoparticles (NPs) and examined their catalytic performance in the cross-coupling reaction of aryl halides with phenylboronic acid and methyl acrylate under mild conditions. To achieve this, MIL-101(Al) was synthesized using a solvothermal method, followed by functionalization with environmentally friendly l-Cysteine (CYS). Subsequently, the MIL-101(Al)-CYS compound was immersed in an ethanolic solution of palladium and stirred overnight. The catalyst exhibited remarkable efficiency (over 90 %) in Suzuki and Heck cross-coupling reactions, demonstrating excellent activity and recyclability. The reactions were conducted in polyethylene glycol 200 (PEG 200), a green reaction medium, at temperatures of 70 °C and 60 °C, with Pd loadings of 0.22 and 0.08 mol%, respectively. MOF-based catalysts, owing to their highly tunable structures and porosity, hold great promise as heterogeneous catalysts in organic reactions.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Palladium on carbon-catalysed carbon-carbon coupling reactions of cyclohexanone (KA oil) and alkyl alcohols for the synthesis of zero net emission jet fuels

The cyclohexanone / cyclohexanol mixture (KA oil) is one of the most produced C6 chemicals worldwide, derived from renewable sources if desired; however, the use of KA oil as a precursor for zero net emission fuels has not been studied in-depth yet, as far as we know. We show here that KA oil is converted to an aromatic-free product mixture compatible with the composition of jet fuels after a series of carbon-carbon coupling reactions, of either KA oil with itself or with bioderived alcohols, in the presence of a commercially available solid-supported palladium on carbon catalyst under basic conditions (KOH). Water is the only by-product of the reaction, and phosphines can be used as ligands to variate the final product composition.

Selective photocatalytic C-C coupling of benzyl alcohol into hydrobenzoin using Pt-deposited CdS nanosheets passivated with cysteamine.

Achieving high selectivity towards hydrobenzoin (HB) from photocatalytic carbon-carbon (C-C) coupling reaction of benzyl alcohol (BzOH) remains a challenge due to side competing reactions and subsequent conversions of HB into its derivatives. In this study, we have developed a high-performance CdS-based photocatalyst for synthesizing HB with precisely controlled surface properties and structure, achieving high selectivity for HB synthesis. We employed strategies such as cysteamine passivation and Pt deposition to address issues related to photogenerated charge trapping and recombination, thereby enhancing the photocatalytic capability of CdS. With optimized Pt/CdS NSs as the photocatalyst, we investigated the impact of the Pt/CdS heterostructure on intermediate reactions, which in turn altered product selectivity. Specifically, excessive Pt suppresses the electron-induced benzaldehyde-to-intermediate reaction by consuming electrons for the competing hydrogen evolution reaction (HER), leading to high selectivity toward benzaldehyde. In contrast, bare CdS without Pt suffers from insufficient charge supply for BzOH conversion due to the charge recombination issue, which promotes the subsequent conversion of HB to its derivatives. Notably, when Pt is precisely loaded to avoid dominant HER competition, the overall reaction rate increases, maintaining high selectivity towards HB and ensuring faster conversion of BzOH to HB rather than subsequent conversions of HB into its derivatives, thereby maximizing the HB yield. Subsequently, we have developed a photocatalyst that achieves a 93.4% conversion of 0.24 mmol BzOH with 85.3% selectivity toward HB under solar simulator irradiation (AM 1.5G). This work is expected to offer instructive guidance on rationally designing the photocatalyst for efficient C-C coupling reactions.

Asymmetric magnetic nanosnowman loaded with AgPd nanocage toward NIR-enhanced catalytic activity.

Although bimetallic noble nanostructures often possess high activity in nanocatalysis, their controllable fabrication, tunable catalytic activity, and easy separation remain significant challenges. In this study, an Fe3O4@AgPd/Polydopamine (Fe3O4@AgPd/PDA) nanosnowman loaded with an AgPd nanocage was designed by a one-step template-disposition-redox polymerization method. The AgPd nanocage endowed the product with high catalytic activity for the reduction of organic pollutants (4-NP, MO, MB). Interestingly, under near-infrared (NIR) light, the catalytic kinetics of the Fe3O4@AgPd/PDA nanosnowman on catalytic reduction of organic pollutants increased by 2.6, 1.57, and 5.45 times, respectively. The asymmetric nanostructure facilitated the separation of electron-hole pairs, promoted electron transfer, and accelerated the catalytic activity. Density functional theory (DFT) analysis indicated that the electron transfer between the AgPd alloy and the Fe3O4 nanosphere played a critical role on the high catalytic activity. Moreover, Fe3O4@AgPd/PDA also demonstrated excellent catalytic activity in the Heck carbon-carbon coupling reaction with a >95% conversion rate and >99% selectivity. Owing to the well-encapsulated PDA shell and outstanding magnetic properties, the Fe3O4@AgPd/PDA nanosnowman exhibited good cyclic catalytic activity. With its multi-mode catalysis, NIR-enhanced catalytic activity, and easy separation, the Fe3O4@AgPd/PDA nanosnowman exhibits great application potential in nanocatalysis.

Theoretical calculations for modeling carbon-carbon coupling reactions on copper surface: A comprehensive review

Theoretical calculations for modeling carbon-carbon coupling reactions on copper surface: A comprehensive review

Palladium nanoparticles immobilized on N-decorated porous carbon as synergistic catalyst for carbon-carbon coupling reactions

N-decorated porous carbon (NDC) was obtained by one step direct pyrolysis of NH2−MIL-125. The content of nitrogen in the NDC-1000 (2 h) was 4.2 %. Palladium nanoparticle was deposited on the NDC by an impregnation strategy. The NDC-1000-Pd catalyst was characterized by powder X-ray diffraction, TEM, XPS and N2 adsorption. Due to the synergetic interaction of metal species and NDC, the catalyst exhibited excellent catalytic performance for Heck coupling and Suzuki-Miyaura reactions. The catalyst can be reused for five cycles without obvious change in its activity.

Controlling C–C coupling reactivity through pore shape engineering of B-doped graphyne family

Graphyne is an interesting carbon allotrope characterized by sp-sp2 hybridized carbon bonds, which allow for structure variability. Though there are studies evaluating the electrical and mechanical properties of various structures, studies utilizing its structural variety toward catalyst applications are minor. In electrocatalytic CO2 reduction reactions (CRR), producing valuable C2+ products, such as C2H4 or C2H5OH, under mild conditions is still challenging. The bottleneck has been assigned to the carbon-carbon (C–C) coupling reaction, such as 2*CO → *OCCO. In this reaction, one requires strong binding to the catalyst to enhance neighboring CO concentration, but at the same time, one needs to have low C–C coupling barriers making the OC-CO bond. Following our previous study, which showed B-doped γ-graphyne can be a catalyst for ethanol production, we conducted theoretical investigations on a range of B-doped graphyne families using density functional theory. Out of the 15 different structures studied, four, 4,12,2-, sR-, γ-, and 6,6,12-graphynes, show promising potential for CRR. B-doped 4,12,2-graphyne, with small square and rectangular pores, had a very low C–C coupling barrier of 0.34 eV with strong 2*CO adsorption (−2.5 eV). Furthermore, our research revealed a correlation between the heat of reaction (2*CO → *OCCO) and the average pore area around the acetylenic linker reaction site. Smaller pores give a favorable orientation of two CO molecules, resulting in low reaction barriers.

Micellar catalysis: Polymer bound palladium catalyst for carbon-carbon coupling reactions in water.

Metallosurfactants, defined here as hydrophobic metal-containing groups embedded in hydrophilic units when dispersed in water, emanate in the formation of metallomicelles. This approach continues to attract great interest for its ability to serve as micellar catalysts for various metal-mediated chemical transformations in water. Indeed, relevant to green chemistry, micellar catalysis plays a preeminent function as a replacement for organic solvents in a variety of chemical reactions. There are several methods for the interaction of metal complexes (catalysts or catalyst precursors) and surfactants for producing micellar aggregates. A very effective manner for achieving this involves the direct bonding of the metal center to the amphiphilic polymeric materials. Herein, we describe the synthesis of a metallosurfactant containing a palladium complex covalently incorporated into a CO2-based triblock polycarbonate derived using a dicarboxylic acid chain-transfer agent. This amphiphilic polycarbonate was shown to self-assemble in water to provide uniform and spherical micelles, where the catalytic metal center is located in the hydrophobic portion of the micelle. The resulting metallosurfactant was demonstrated to effectively catalyze carbon-carbon coupling reactions at very low catalyst loadings.

Catalytic Asymmetric Synthesis of Zinc Metallacycles.

Transition-metal-catalyzed reductive coupling reactions of alkynes and imines are attractive methods for the synthesis of chiral allylic amines. Mechanistically, these reactions involve oxidative cyclization of the alkyne and the imine to generate a metallacyclic intermediate, which then reacts with H2 or a H2 surrogate to form the product. As an alternative to this hydrogenolysis pathway, here we show that transmetalation to zinc can occur, forming a zinc metallacycle product. This organozinc product serves as a versatile nucleophile for carbon-carbon and carbon-heteroatom coupling reactions. Mechanistic studies based on isotopic labeling experiments and DFT calculations suggest that the key transmetalation step occurs between a Co(II) species and ZnCl2.

Palladium immobilized in Fe3O4@PEG/cryptand 222 core-shell nanostructure for enhanced cross-coupling reactions under sonication

The ultrasound-assisted reaction has been regarded as a promising strategy for boosting cross-coupling reactions. Herein, we described the ultrasound-assisted carbon-carbon, carbon-nitrogen, and carbon-oxygen coupling reactions via Pd@Crypt-222/Fe3O4@PEG core-shell nanostructure. First, the Fe3O4@PEG core-shell nanostructure was prepared and then cryptand 222 (Crypt-222) ligand was decorated onto the surface catalyst for coordinating palladium (Pd) ions. Well-affinity Crypt-222 ligand toward adsorption of Pd ions had a prominent role in the long-term stability of Pd. X-ray diffraction (XRD) pattern and Fourier transform infrared spectroscopy (FT-IR) spectra revealed that Crypt-222 ligand and Pd ions have successfully stabilized on the surface of Fe3O4@PEG. The synergistic effect of the catalyst with ultrasound irradiation enhanced the activity of the Pd ions in the cycle of the cross-coupling reactions, which significantly decreased the reaction time and temperature. Meanwhile, the results revealed that the proposed nanostructure could be conveniently recovered by applying an external magnetic field. The present study not only provides new horizons into the design of magnetic-based core-shell structures but also develops ultrasound-assisted reactions.

Facile Synthesis Hyper-Crosslinked PdFe Bimetallic Polymer as Highly Active Catalyst for Ullmann Coupling Reaction of Chlorobenzene.

The synthesis of efficient and sustainable heterogeneous Pd-based catalysts has been an active field of research due to their crucial role in carbon-carbon coupling reactions. In this study, we developed a facile and eco-friendly in situ assembly technique to produce a PdFe bimetallic hyper-crosslinked polymer (HCP@Pd/Fe) to use as a highly active and durable catalyst in the Ullmann reaction. The HCP@Pd/Fe catalyst exhibits a hierarchical pore structure, high specific surface area, and uniform distribution of active sites, which promote catalytic activity and stability. Under mild conditions, the HCP@Pd/Fe catalyst is capable of efficiently catalyzing the Ullmann reaction of aryl chlorides in aqueous media. The exceptional catalytic performance of HCP@Pd/Fe is attributed to its robust absorption capability, high dispersion, and strong interaction between Fe and Pd, as confirmed by various material characterizations and control experiments. Furthermore, the coated structure of a hyper-crosslinked polymer enables easy recycling and reuse of the catalyst for at least 10 cycles without any significant loss of activity.

Multi-radicals mediated one-step conversion of methane to acetic acid via photocatalysis

One-step photocatalytic methane conversion to acetic acid possesses high economic and academic value, and carbonyl species (CO, CO2) are usually necessary to be introduced into the reaction system to realize the carbon-carbon coupling reaction, which requires high energy input. In this work, a composite photocatalyst (Ag/AgCl-WO3-x) was constructed to successfully realize the one-step photocatalytic conversion of CH4 to CH3COOH without addition of carbonyl species. Chlorine radicals and hydroxyl radicals could be produced simultaneously under light irradiation over Ag/AgCl. Specifically, CH4 could undergo the hydrogen atom transfer reaction with chlorine radicals to produce methyl species, and hydroxyl radicals could mineralize CH4 to produce carbonyl species. After further combining WO3−x, carbon-carbon coupling reaction between carbonyl and methyl species occurred to effectively produce CH3COOH (188.5 μmol·gcat−1·h−1). This work provides a new prospect of designing photocatalytic system to realize CH4 conversion to C2 products.

Development of an in vitro method for activation of X-succinate synthases for fumarate hydroalkylation

Anaerobic microbial degradation of hydrocarbons is often initiated through addition of the hydrocarbon to fumarate by enzymes known as X-succinate synthases (XSSs). XSSs use a glycyl radical cofactor, which is installed by an activating enzyme (XSS-AE), to catalyze this carbon-carbon coupling reaction. The activation step, although crucial for catalysis, has not previously been possible invitro because of insolubility of XSS-AEs. Here, we take a genome mining approach to find an XSS-AE, a 4-isopropylbenzylsuccinate synthase (IBSS)-AE (IbsAE) that can be solubly expressed in Escherichia coli. This soluble XSS-AE can activate both IBSS and the well-studied benzylsuccinate synthase (BSS) invitro, allowing us to explore XSSs biochemically. To start, we examine the role of BSS subunits and find that the beta subunit accelerates the rate of hydrocarbon addition. Looking forward, the methodology and insight gathered here can be used more broadly to understand and engineer XSSs as synthetically useful biocatalysts.

Mechanistic Views on the Manganese Catalyzed Homogeneous Coupling Reactions

Abstract: The transition metal-catalyzed C-C and C-X (X=heteroatom) homo and crosscoupling reactions were pioneered as a momentous strategy for the total synthesis of natural products, agrochemicals, pharmaceuticals, etc. Among the various transition metal-catalyzed reactions, manganese catalysis held a distinctive identity owing to its earth-abundance and eco-friendliness apart from its unique characteristics. Despite having many synthetic advancements, exploiting manganese as a catalyst for coupling reactions has recently gained pivotal gravity. An in-depth comprehension of the molecular mechanism of the chemical reaction will provide further insight to optimize the reaction conditions. The mechanisms adopted by Mn-catalyzed couplings are found to differ from other first-row transition metal counterparts. Hence in this article, we provide the state-of-the-art on the detailed theoretical aspects of manganese-catalyzed carbon-carbon (C-C) and carbon-heteroatom (C-X; X=Si) coupling reactions.