Sonogashira Cross-coupling Reaction Research Articles

Design of highly effective organic catalyst for hydrazine electrooxidation: Iodobenzo[b]furan derivatives

In this study, we investigate the electrochemical characteristics of 2-aryl/alkyl-3-iodobenzo[b]furans as anode catalysts for hydrazine (N2H4) fuel cells. Cyclic voltammetry (CV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) techniques are employed to investigate the performance of these heteroaromatic compounds. The results demonstrate the promising potential of the 2-aryl/alkyl-3-iodobenzo[b]furans in fuel cell technology. Among the tested organic catalysts (2a, 2b, 2c, 2d, and 2e), 2a exhibited the highest electrocatalytic activity, giving a total current density of 26.62 mA/cm2 within the potential range of −0.4 to −0.8 V. 2-aryl/alkyl-3-iodobenzo[b]furans were synthesized by using palladium/copper-catalyzed Sonogashira cross-coupling reactions, followed by electrophilic cyclization with iodine (I2). All products were characterized using 1H and 13C NMR spectroscopy, confirming their structures and providing insights into their chemical properties.

Design and Asymmetric Control of Orientational Chirality by using the Combination of C(sp2)-C(sp) Levers and Achiral N-Protecting Group.

New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinylimine-directed nucleophilic addition/oxidation, Suzuki-Miyaura and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp2)-C(sp) axis] and tBuSO2- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner. seventeen examples of multi-step synthesis were obtained in modest to good chemical yields and complete orientational selectivity.

Pd-Isatin-Schiff base complex supported on graphene oxide as a catalyst for the Sonogashira cross-coupling reaction

The study reports on the synthesis and characterization of palladium-Isatin-Schiff base complex supported on graphene oxide (Pd-Isatin-Schiff base@rGO), as well as its application in the Sonogashira cross-coupling reaction. The catalyst was easily prepared by a simple method through modification of GO with (3-aminopropyl) triethoxysilane (APTES) as a linker. The reaction of free amine groups with isatin allowed the synthesis of Isatin-Schiff base@rGO. The subsequent complexation/immobilization of palladium provided the Pd-Isatin-Schiff base@rGO nanocomposite with a Pd(II) to Pd(0) ratio=1.17. The prepared Pd-Isatin-Schiff base@rGO nanocomposite was fully characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), CHN elemental analysis, scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), high-resolution transmission electron microscope (HRTEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma optical emission spectroscopy (ICP-OES) to establish its structure and composition. This heterogeneous nanocomposite catalyst was found very efficient for the cross-coupling reaction of an alkyne and an aryl halide, generating a high yield of coupling products (80–95 %) after 1 h. A reusability study revealed that the Pd-Isatin-Schiff base@rGO composite could be recycled for six consequent cycles without significant loss of its activity. However, after six cycles, the yield of 1,2-diphenylethyne as the coupling product decreased slightly from 93 % to 85 % and a decrease 8 wt.% in the Pd content was observed using ICP analysis.

Difluoro Dipyridomethene Boron Complexes: Synthesis, Characterization, and Ab Initio Calculations.

Molecular engineering studies on the meso-cyano difluoro dipyridomethene boron complexes are presented and two series (a and b) of novel fluorophores are extensively studied. Halogenated derivatives were reacted under Suzuki-Miyaura or Sonogashira cross coupling reactions to introduce electron-donating or electron-withdrawing functional groups on positions 1 and 2 of the aromatic ligand. All derivatives were obtained in 14-90% yields and studied in detail by structural, photophysical, and computational analyses. Both series display excellent emissive properties in solution with blue to orange fluorescence emission upon blue light absorption and promising features as solid emitters. All the spectroscopic measurements are supported and confirmed by first-principles theoretical calculations combining TD-DFT and CC2. Series b, featuring an aryl substituent onto position 1 of the aromatic core, showed significantly large Stokes shifts values.

C1 symmetric dual-carboxyl-functionalized BODIPY dye: Synthesis, photophysical properties, and self-assembly behavior via hydrogen bonding

A BODIPY derivatives 3 with phenylethynyl bridging two carboxyl groups was synthesized via Sonogashira cross-coupling reaction. The structure was characterized by 1HNMR and HRMS. Its photophysical properties and aggregation behavior in solution were studied by UV–Vis absorption and fluorescence spectroscopy. The compound 3 displays strong absorption and high fluorescence quantum yield. The investigations of UV–Vis and emission also revealed the formation of self-assembled structures in the solid state or liquid/state with translationally slipped π-stacks of BODIPY units driven by hydrogen bonding between the carboxyl groups. The thermodynamic properties of the BODIPY derivative were carried out by DSC and TGA, indicating it possesses high thermal stability. In addition, the self-assembly of the BODIPY derivative functionalized with two carboxyl groups was explicitly investigated by using scanning tunneling microscopy (STM). The highly ordered supramolecular self-assembly monolayers endow the novel carboxyl functionalized BODIPY with good potential for application in organic devices.

Desulfitative Sonogashira cross-coupling of thiopyronin for the synthesis of NIR arylacetylene-containing rhodamines.

A classical, safe and efficient red-shift strategy contributing to NIR arylacetylene-containing rhodamines has been developed via the desulfitative Sonogashira cross-coupling reaction of thiopyronin for the first time, exhibiting a broad substrate scope with good yields. In addition, compound 3m shows great potential for application as a singlet oxygen probe, demonstrating the practicality of the method.

NIR-absorbing TCBD and cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD bridged derivatives of 1,1′-bis(N,N-dimethylaniline)-substituted ferrocene

Symmetrical and unsymmetrical donor-acceptor (D–A) based chromophores were designed and synthesized by the Pd–catalyzed Sonogashira cross–coupling reaction of 1,1′-diiodoferrocene with (4-N,N-dimethylaminophenyl)ethyne followed by [2+2] cycloaddition-retroelectrocyclization reaction with tetracyanoethylene (TCNE) or 7,7,8,8-tetracyanoquinodimethane (TCNQ). Ferrocene was used as a central donor unit and 4-(N,N-dimethylamino)phenyl group as the end-capping donor. Herein, we report the cycloaddition-retrocyclization reaction of TCNE/TCNQ groups on the disubstituted ferrocene containing more than one triple bond to get disubstituted tetracyanobutadiene (TCBD) and cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD products. The effect of the conjugation length and different π–acceptor linkers were investigated by photophysical, redox and computational studies. The redox study reveals multiple oxidation waves corresponding to donor moieties (ferrocene and 4-(N,N-dimethylamino)phenyl group) and reduction waves corresponding to acceptor units (TCBD / cyclohexa-2,5- diene-1,4-diylidene-expanded TCBD). The thermogravimetric analysis data shows that the compounds exhibit high thermal stability. The computational studies reveal HOMO-LUMO gaps consistent with the experimentally obtained data.

Synthesis and antituberculosis activity of new 5-alkynyl derivatives of 2-thiouridine: application of new scaffold

We herein describe new potent inhibitors of mycobacteria based on 5-substituted 2-thiouridine derivatives. A series of new 5-alkynyl-substituted 2-thiouridine derivatives were synthesized via palladium-catalysed Sonogashira cross-coupling reaction of 5-iodo-2-thiopyrimidine base with terminal acetylenes with good yields in DMF at room temperature. It was found that sulfur atom in C2 position of pyrimidine ring had no impact on yields of target compounds. All obtained compounds were evaluated for their antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis at concentrations of 0.1-100 µg/ml using MABA test. Synthesized nucleosides showed high antimycobacterial activity against Mycobacterium bovis and Mycobacteri um tuberculosis. The obtained MIC50 values of 2-thionucleosides 14, 15 and 16 (0.28-0.75 µg/ml) significantly exceed characteristics of reference drug rifampicin, D-cycloserine and isoniazid, which gives prerequisites for further more detailed studies.

Copper- and Ligand-Free Sonogashira Cross-Coupling: Access to Novel 3-Aminoindole Derivatives and Their Biological Evaluations

Indole-containing compounds are widely distributed in the plant and animal kingdom, and their biological activity and pharmacological properties have prompted research into their chemical properties. This study developed a one-pot methodology for the synthesis of 3-aminoindole derivatives using copper- and ligand-free Sonogashira cross-coupling reaction conditions. The synthesised 3-aminoindole derivatives were confirmed using spectroscopic techniques. The resulting 3-aminoindole derivatives were biologically evaluated against Mycobacterium tuberculosis and Plasmodium falciparum. For example, indole derivatives 10a (7.813 µM) and 10j (8.332 µM) were the most active derivatives in the CAS and ADC media, respectively.

Recent Advances in Transition-Metal-Catalyzed Sonogashira Cross-Coupling Reactions of Alkyl Electrophiles

AbstractCatalytic Sonogashira cross-coupling reactions represent an efficient and versatile approach for constructing complex alkynes from readily available starting materials. Despite notable progress in this field, the development of transition-metal-catalyzed Sonogashira cross-coupling reactions of alkyl electrophiles remains limited. This limitation primarily stems from the low reactivity and pronounced propensity of these compounds towards β-H elimination. To overcome these challenges, researchers have investigated the use of palladium, nickel, and copper catalysts for Sonogashira reactions of alkyl electrophiles. Furthermore, significant strides have been made in achieving asymmetric Sonogashira cross-coupling reactions of electrophiles. This short review provides an overview of recent breakthroughs in this area.1 Introduction2 Palladium-Catalyzed Sonogashira Cross-Coupling of Alkyl Halides3 Nickel-Catalyzed Sonogashira Cross-Coupling of Alkyl Halides4 Copper-Catalyzed Sonogashira Cross-Coupling of Alkyl Electrophiles4.1 Copper-Catalyzed Racemic Sonogashira Cross-Coupling of Alkyl Electrophiles4.2 Copper-catalyzed Asymmetric Sonogashira Cross-Coupling of Alkyl Electrophiles5 Conclusions and Perspectives

Pd@HKUST-1@Cu(II)/CMC composite bead as an efficient synergistic bimetallic catalyst for Sonogashira cross-coupling reactions

We fabricated an efficient Pd@HKUST-1@Cu(II)/CMC composite bead catalyst through an innovative strategy based on the unique properties of metal-organic frameworks (MOFs) and carboxymethylcellulose (CMC). In this strategy, HKUST-1 MOFs were grown in-situ on the surface of micrometer-sized Cu-based CMC beads (Cu(II)/CMC), then Pd(II) ions were incorporated into the pores of the MOF and further be partially reduced to Pd(0) NPs, which is an active species for oxidative addition with aryl halides in Sonogashira reactions. The micron-sized Cu(II)/CMC beads were formed through inter/intramolecularly crosslinking facilitated by Cu(II) ions, which was achieved by the metathesis of Cu(II) with numerous carboxylic groups of CMC. Such Cu(II)/CMC bead offers many Cu(II) ions as interaction sites for in-situ nucleation and growth of HKUST-1 MOFs. The architecture and composition of the prepared Pd@HKUST-1@Cu(II)/CMC composite were fully verified by various techniques such as FTIR, XRD, TGA, BET, XPS, SEM, TEM, EDX, and elemental mapping analysis. This novel composite bead was applied as an efficient and reusable heterogeneous Pd/Cu bimetallic catalyst for Sonogashira reactions, decarbonylative Sonogashira reaction, and Sonogashira cyclization tandem reactions. The catalyst is readily isolated by simple filtration, and can be reused for five consecutive runs with retaining its activity and structural integrity.

Stereoselective Synthesis, Pro-resolution, and Anti-inflammatory Actions of RvD5n-3DPA.

The methyl ester of resolvin D5n-3DPA, a lipid mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid, was stereoselectively prepared in 8% yield over 12 steps (longest linear sequence). The key steps for the introduction of the two stereogenic secondary alcohols were an organocatalyzed oxyamination and the Midland Alpine borane reduction. For the assembly of the carbon chain, the Sonogashira cross-coupling reaction and the Takai olefination were utilized. The physical properties, including retention time in liquid chromatography and tandem mass spectra, of the synthetic material were matched against material from human peripheral blood and mouse infectious exudates. Synthetic RvD5n-3DPA, obtained just prior to biological experiments, displayed potent leukocyte-directed activities, upregulating the ability of neutrophils and macrophages to phagocytose bacteria, known as hallmark bioactions of specialized pro-resolving endogenous mediators.

A Stereoselective Entry to Enantiopure (S)-2-Amino-2-methyl-5-arylpent-4-ynoic Acids and Evaluation of Their Inhibitory Activity against Bacterial Collagenase G

Nowadays, amino acids (AAs) and peptides with bulky side chains hold significant interest for organic synthesis and the modern pharma industry. Non-proteinogenic (or unnatural) AAs are key building blocks used for obtaining pharmaceutically relevant peptides and for the development of chiral molecular catalysts, and they are extensively used in the total synthesis of complex natural compounds. Thus, an elaboration of cost-effective methods for the preparation of novel unnatural AAs to increase their structural diversity is highly desirable. In this context, herein, we present an asymmetric metal-templated synthesis of a number of enantiomerically pure (S)-2-amino-2-methyl-5-arylpent-4-ynoic acids starting from commercially available reagents and Belokon’s chiral auxiliary (S)-BPB, namely (S)-2-(N-benzylprolyl)aminobenzophenone. The construction of a chiral Ni(II) complex from alanine (Ala) and the subsequent propargylation, arylation by the Sonogashira cross-coupling reaction using various aryl halides, and, finally, an acidic decomposition of the obtained complexes deliver to the target complex α,α-disubstituted AAs featuring a triple bond in a side chain. Next, the Fmoc-protected α-AAs and dipeptide were synthesized. Finally, we examined the obtained α-AAs and peptide as collagenase inhibitors.

Designing PdxCuy octahedra alloy nanocatalysts supported on solid substrates for solvent-free sonogashira cross-coupling reaction: Rational optimization of metal precursors

The current research details a scientific inquiry into an economic, reproducible, and adaptable synthetic process for the formation of PdxCuy octahedra (Oh) alloy nanocatalysts. Herein, several alloys such as Pd3Cu7, Pd4Cu6, Pd5Cu5, Pd6Cu4, and Pd7Cu3 are synthesized by altering the metal precursors quantities, resulting in a specific octahedral shape for all the ratios. After a thorough optimization study, Pd6Cu4 alloy was selected and anchored onto three solid substrates to achieve Pd6Cu4@hBNNs, Pd6Cu4@ZrO2 and Pd6Cu4@GONs nanocatalysts. Furthermore, the nanocatalysts were investigated for the Sonogashira cross-coupling reaction under solvent-free conditions, with the 15 wt% of the metal-support ratio of Pd6Cu4@hBNNs exhibiting remarkable catalytic activity when compared to the other two supported nanocatalysts. In advance, highly active Pd6Cu4@hBNNs nanocatalyst has many advantages, including mild reaction conditions, benign and minimum reaction duration. Moreover, the catalyst showed an efficient yield of 95 % for the model Sonogashira cross-coupling and considerable recyclability up to the 8th consecutive cycle achieving a 65 % yield. The outstanding performance of this economically viable nanocatalyst is most likely influenced by the synergistic effect of the catalyst and its strong metal-support contact.

Dimeric Calix[4]arenes, Synthesis and their Application: A Review

Abstract: Calix[n]arene is an attractive host for molecular recognition due to its accessibility through the hollow cavity and shallow bowl shape and has been used as a receptor over the last 30 years. Calix[n]arene has a small cavity, so designing a flexible molecule to recognize nano to large biomolecules is a challenging goal in host-guest chemistry. Dimeric calix[n]arene is formed by linking two calix[n]arene sub-units to each other. Their considerable structural features and relative diversity of modifying the upper or lower rim represent outstanding and greatly adaptive structures for designing bulky and complex building blocks adequate for selfassembly and molecular recognition. Their ability to form supramolecular structures for a wide range of applications, including the recognition of nano-molecules and large biological molecules, has been extensively studied. This review details the progress of the host-guest chemistry of dimeric calix[n]arenes, emphasizing the synthetic pathways employed for their production and their self-assembly properties. Dimerization of calix[n]arene occurs in two ways (1-through non-covalent bonding such as H-bonding or self-assembly, and 2-through covalent bond formation such as amide bond formation, multi-component reactions and Sonogashira cross-coupling reaction and metathesis reactions). In this work, we focused on dimerization through covalent bond formation, due to having more applications and diverse synthetic applications.

Triazole-Appended Glycohybrid/CuI-Catalyzed C-C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars.

This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60-70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope.

Sonogashira coupling reactions with ligand-free heterogeneous nanoporous Pd catalyst

The Sonogashira coupling reaction is one of the most important protocols for the production of aryl alkynes. In order to solve the problems existing in Sonogashira cross-coupling reaction, according to the application of nanoporous palladium in Suzuki and Heck cross-coupling reactions, nanoporous palladium was used as the sustainable catalyst for the Sonogashira cross-coupling reaction. A sustainable catalyst system was tested and optimized without cuprous ion, phosphine ligand, or amine additives. Nanoporous palladium catalyst remained stable over five cycles without significant leaching or loss of catalytic activity, and the desired alkynes were obtained in high yields.

Modular Synthesis of Phosphino Hydrazones and Their Use as Ligands in a Palladium-Catalysed Cu-Free Sonogashira Cross-Coupling Reaction.

Invited for this month's cover is the group of Evamarie Hey-Hawkins at Leipzig University. The cover picture shows the three different bonding modes (mono-, bi- and tridentate) of the modular ligand towards palladium(II) or platinum(II), illustrated with Winston who kindly served as the model. The cat has three binding sites (mouth, front paws and hind paws = P, N and pyridine) to bind the metal dichloride fragment. When all three are used in a tridentate bonding mode, one chlorido ligand is cleaved off. Cover design by Dr. Christoph Selg. More information can be found in the Research Article by Evamarie Hey-Hawkins and co-workers.

New Mechanistic Insights into the Copper-Free Heck–Cassar–Sonogashira Cross-Coupling Reaction

New Mechanistic Insights into the Copper-Free Heck–Cassar–Sonogashira Cross-Coupling Reaction

Synthesis and Fluorescence Properties of Imidazopyridine-Linked Coumarins via Tandem C(sp2)-H Functionalization/Decarboxylation Reaction.

A catalyst-, oxidant-free and green synthetic route for direct access to a series of novel imidazopyridine-linked coumarins has been devised through tandem C(sp2)-H functionalization/decarboxylation reaction in ethyl acetate as a sustainable medium. Moreover, the utilities of ensured products in further organic synthesis were conducted by Suzuki-Miyaura and Sonogashira cross-coupling reactions. The fluorescence characteristics of the produced molecules are appropriate, and the synthesized scaffolds could promisingly garner future attention in clinical diagnostics and bioimaging research.