Sonogashira Coupling Research Articles

Synthese und photophysikalische Eigenschaften von lumineszenten Phenothiazinyl‐Merocyanin‐substituierten Polyacetylenen

AbstractEine neue Generation löslicher Phenothiazinyl‐Merocyanin‐substituierter Polyacetylene wurde mittels Rhodium‐katalyisierter Polymerisation der entsprechenden 3‐Ethinyl‐Phenothiazine dargestellt. Die Monomere sind über Sonogashira‐Kupplung und Knoevenagel‐Kondensation zugänglich. UV/Vis‐ und fluoreszenzspektroskopische Untersuchungen der 7‐Acceptor‐substituierten Phenothiazinyl‐Polyacetylene zeigen, dass diese Polymere mit konjugiert verknüpften Merocyaninen in Lösung mit positiver Emissionssolvatochromie lumineszieren und in bestimmten Fällen eine ausgeprägte Festkörperlumineszenz aufweisen.

PdII Triazolylidene Complexes: Ancillary Ligand Dependent Catalytic Applications in Sonogashira Coupling and α‐Arylation Reactions under Copper‐Free Conditions

AbstractComplexes ofN‐heterocyclic carbenes have become an irrefutable class of molecules for the researchers in the field of organocatalysis. They rank as one of the potent tools in organic chemistry, which have a wide range of uses in various commercially important processes. Palladium(II) mesoionic carbene (MIC) complexes embedded with PPh3 as an ancillary ligand appeared to be efficient catalysts for the aforementioned purpose. Two new triazolylidene‐based palladium(II) complexes bearing either Py or PPh3 as an ancillary ligand were synthesized, with chirality present at one of the nitrogen atoms of the triazolylidene moiety. The MIC unit in these complexes possesses a mesityl group at the C‐wingtip and 1‐(1‐naphthyl)ethyl substitution at the N‐wingtip. NMR spectroscopy and ESI mass spectrometry were utilized to analyze these complexes. For the determination of the structure of the palladium(II) complex possessing mixed MIC and PPh3 donor ligands, single crystal X‐ray diffraction was utilized. The new complexes were employed in α‐arylation reaction and Sonogashira coupling reactions under copper‐free conditions. While studying their catalytic activity, it was brought to the conclusion that the PdII MIC complex having PPh3 as an ancillary ligand surpassed the complex with Py as an ancillary ligand.The catalytic results of these complexes are also correlated with cyclic voltammetric (CV) data.

ZrO2 Supported Cu Nanoparticles for Sonogashira and Ullmann Coupling Reactions Under Palladium-Free Conditions

ZrO2 Supported Cu Nanoparticles for Sonogashira and Ullmann Coupling Reactions Under Palladium-Free Conditions

Tuning emission of luminescent 2-7 disubstituted sila-and germafluorenes with –(trifluoromethyl)phenyl, -(malononitrile)phenyl, and -nitrobenzene substituents

2,7-Disubstitution and DFT-guided design have been used to tune emission wavelengths for three new fluorescent 2,7-alkynyl(aryl)-3,6-dimethoxy-9,9-diphenyl-sila- and germafluorenes. Two germafluorenes with trifluoromethyl phenyl and nitrobenzene substituents were prepared using a Pd-catalyzed Sonogashira coupling reaction to incorporate alkynyl(aryl) groups at the 2,7-positions of the ring. Another new silafluorene was prepared by modifying a benzaldehyde-substituted silafluorene to incorporate a malononitrile group. These compounds were characterized utilizing multinuclear NMR, UV–Vis, and fluorescence spectroscopic techniques. The germafluorene with the trifluoromethyl phenyl substituent was also characterized via elemental analysis and X-ray crystallography. These metallafluorenes (MFs), which are yellow or red-orange crystals in the solid state, showed a wide range of quantum yields and spectroscopic features, with the malononitrile-containing MF exhibiting significantly red-shifted emission relative to other MFs. These data demonstrate the value in applying DFT to MF design and the dramatic impact the 2,7-substituent has on the optical properties of this class of compounds.

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions.

The pyridine-3,5-dicarbonitrile moiety has gained significant attention in the field of materials chemistry, particularly in the development of heavy-metal-free pure organic light-emitting diodes (OLEDs). Extensive research on organic compounds exhibiting thermally activated delayed fluorescence (TADF) has led to numerous patents and research articles. This study focuses on the synthesis and investigation of the semiconducting properties of polyaromatic π-systems containing two and three fragments of pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile. The compounds are synthesized by Sonogashira coupling reactions and characterized by steady-state and time-resolved luminescence spectroscopy. The compounds show efficient intramolecular charge transfer (ICT) from the donor to the acceptor. The photoluminescence (PL) spectra of the solutions of the compounds showed non-structured emission peaks in the visible region, which are attributed to ICT emission. The PL intensities of the solutions of the compounds are enhanced after deoxygenation, which is indicative of TADF. The photoluminescence quantum yields and TADF properties of the compounds are sensitive to the medium. Cyclic voltammetry measurements indicate good hole-blocking and electron-injecting properties due to their high ionization potentials. Photoelectron spectroscopy and time-of-flight measurements reveal good electron-transporting properties for one of the compounds. In general, polyaromatic π-systems with pyridine-3,5-dicarbonitrile fragments demonstrate promising potential for use in organic electronic devices, such as OLEDs.

Distinguishing Between Linear and Nonlinear (Cooperative) Mechanisms of Substrate Activation Under “Ligand- and Copper-Free” Conditions of the Sonogashira Reaction

Distinguishing Between Linear and Nonlinear (Cooperative) Mechanisms of Substrate Activation Under “Ligand- and Copper-Free” Conditions of the Sonogashira Reaction

Reaction Environment Design for Multigram Synthesis via Sonogashira Coupling over Heterogeneous Palladium Single-Atom Catalysts.

Single-atom heterogeneous catalysts (SACs) attract growing interest in their application in green chemistry and organic synthesis due to their potential for achieving atomic-level precision. These catalysts offer the possibility of achieving selectivity comparable to the traditionally applied organometallic complexes, while enhancing metal utilization and recovery. However, an understanding of SAC performance in organic reactions remains limited to model substrates, and their application as drop-in solutions may not yield optimal activity. Here, we investigate the previously unaddressed influence of the reaction environment, including solvent, base, cocatalyst, and ligand, on the performance of a palladium SAC in Sonogashira-Hagihara cross-couplings. By examining the effects of different solvents using the established criteria, we find that the behavior of the SAC deviates from trends observed with homogeneous catalysts, indicating a distinct interplay between heterogeneous systems and the reaction environment. Our results illustrate the satisfactory performance of SACs in cross-couplings of aryl iodides and acetylenes with electron-withdrawing and -donating groups, while the use of bromides and chlorides remains challenging. Extending the proof-of-concept stage to multigram scale, we demonstrate the synthesis of an intermediate of the anticancer drug Erlotinib. The catalyst exhibits high stability, allowing for multiple reuses, even under noninert conditions. Life-cycle assessment guides the upscaling of the catalyst preparation and quantifies the potential environmental and financial benefits of using the SAC, while also revealing the negligible impact of the PPh3 ligand and CuI cocatalyst. Our results underscore the significant potential of SACs to revolutionize sustainable organic chemistry and highlight the need for further understanding the distinct interplay between their performance and the reaction environment.

Copper Nanoparticles on Montmorillonite K-10: A Versatile Catalyst for the One-Pot Synthesis of 3,5-Disubstituted Isoxazoles Using Various Methodologies

AbstractA readily prepared and versatile heterogeneous catalyst composed of copper nanoparticles supported on montmorillonite K-10 (CuNPs/MK-10) has proven to be highly effective in catalyzing the synthesis of isoxazoles through various one-pot methodologies with high atom economy. These methodologies allow for the use of readily available starting materials, including aldehydes and alkynes through 1,3-dipolar cycloaddition reactions, as well as via cycloisomerization of ynones. Additionally, the CuNPs/MK-10 catalyst promoted the in situ formation of the ynones via an acyl Sonogashira coupling. Furthermore, a three-step one-pot methodology was also developed, starting from carboxylic acids and involving the in situ generation of acyl chlorides.

Sequence Information Transfer in Oligoarylacetylenes

AbstractThe ability of genetic biopolymers to store and transfer information provides the mechanism for the evolution of function from a population of sequences. Synthetic polymers with the ability to transmit information are exceedingly rare. This work demonstrates template‐directed information transfer in oligoarylacetylene trimers that use reversible covalent bonds to form base pairing interactions. Information was encoded as a sequence of aniline and benzaldehyde subunits linked together by a diethynylbenzene backbone. Trimers formed sequence‐specific, imine‐linked monomer‐template complexes, which could be oligomerized using palladium mediated Sonogashira coupling to generate daughter trimers with complementary sequences.

Palladium nanoparticles on polydimethylsiloxane film for C−C coupling reactions, and catalytic reduction of organic pollutants in water

AbstractIn this study, we present a novel method for immobilizing Palladium nanoparticles (Pd NPs) onto a polydimethylsiloxane (PDMS) support (Pd NPs@PDMS). To enhance the stability of Pd NPs on the PDMS surface, we functionalized a PDMS thin film with amine groups. The structure and morphology of the resulting Pd NPs@PDMS material were characterized using various techniques, including field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and X‐ray photoelectron spectroscopy (XPS) measurements. Furthermore, we investigated the catalytic performance of the Pd NPs@PDMS nanocatalyst for the reduction of well‐known environmental pollutants, such as 4‐nitrophenol (4‐NP), 2‐nitrophenol (2‐NP), 4‐nitroaniline (4‐NA), Methyl Orange (MO), Methylene Blue (MB), and Congo Red (CR), in the presence of sodium borohydride (NaBH4) at room temperature (RT). Additionally, we explored the application of the prepared nanocatalyst in carbon‐carbon (C−C) coupling reactions, specifically Suzuki Miyaura and Sonogashira reactions. The results obtained in this study demonstrated the high efficiency and environmentally friendly nature of Pd NPs@PDMS as a catalyst for both C−C coupling reactions and the degradation of organic pollutants.

Air Tolerant Cadiot-Chodkiewicz and Sonogashira Cross-Couplings.

Cadiot-Chodkiewicz cross-couplings generate an unsymmetric buta-1,3-diyne by way of a Cu(I)-catalyzed coupling between a terminal alkyne and a 1-haloalkyne. Despite their widespread use, Cadiot-Chodkiewicz reactions are plagued by the generation of symmetric buta-1,3-diyne side products, formed through competing: (a) formal reductive homo-coupling of the 1-haloalkyne and (b) oxidative (Glaser-Hay/Eglinton) homo-coupling of the terminal alkyne. To overcome this issue, a large excess of one of the two reacting alkynes is commonly deployed, and difficult separations of cross- and homo-coupled products are often encountered. Here, we demonstrate that the use of ascorbate as a reductant leads to a suppression of these unwanted side reactions, hence permitting excellent yields with a roughly stoichiometric ratio of reactants. The procedure also avoids an inert gas atmosphere and uses a sustainable solvent. A similar approach is effective for cross-couplings involving a Pd(0)/Pd(II) catalytic cycle, with air tolerant Sonogashira couplings also established.

Controlling the light-induced structural isomerism of lipophilic azo-bridged porphyrin dimer via steric hindrance modulated functional linkers

Herein, two azo-bridged porphyrin dimers were synthesized via Sonogashira and Suzuki coupling reactions. The relationship between molecular structures and electronic structures was investigated by spectroscopic and electrochemical characterizations. In addition, the light-induced structural isomerism of lipophilic azo-Bridged porphyrin dimer could be controlled via steric hindrance modulated functional linkers, and it can only be succeeded in the case of expanded azo-bridged porphyrin dimer.

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

Distinguishing between Linear and Non-Linear (Cooperative) Substrate Activation Mechanisms in the Sonogashira Reaction under “Ligand-Free” and “Copper-Free” Conditions

The results are presented on the comparative studies of the differential selectivity patterns in the Sonogashira reaction with a pair of competing aryl acetylenes in the “ligand-free” and “copper-free” conditions when varying the nature and concentration of aryl halides and base. The revealed sensitivity of the differential selectivity of competing aryl acetylenes to aryl halide nature unambiguously indicated that the substrates were activated through linear mechanism from kinetic view. An absence of any influence of the nature and concentration of the base on the differential selectivity of competing aryl acetylenes indicated the irreversible character of the step of their activation.

Construction of three-dimensional porous organic polymers with enhanced CO2 uptake performance via solid-state thermal conversion from tetrahedral benzoxazine-linked precursor

Porous organic polymers (POPs) with three-dimensional (3D) linkages have drawn great interest due to their potential applications in separation, adsorption, and sensing fields. Herein, a new 3D benzoxazine (BZ)-linked porous organic polymer (TPM-BZ-Py POP) was synthesized by linking a tetrahedral benzoxazine (TPM-BZ-Br4) with tetraethynylpyrene (Py-T) via Sonogashira coupling. Specifically, the synthesis of the tetrahedral benzoxazines with four oxazine rings in a single monomer involved the utilization of Schiff base formation, NaBH4 reduction as well as Mannich condensation reactions. To confirm the chemical structure of the benzoxazine monomers and their corresponding polybenzoxazines, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), and carbon nuclear magnetic resonance (13C NMR) spectroscopy techniques were employed. The pore volume and specific surface area of the 3D TPM-BZ-Py POP were determined through N2 adsorption/desorption isotherms, and they were found to be 0.52 cm3/g and 185 m2/g, respectively. In addition, the solid-state chemical transformation occurred during thermal ring-opening polymerization (ROP), and the resulting 3D poly(TPM-BZ-Py) POP displayed higher CO2 capture ability (1.81 mmol/g) compared with TPM-BZ-Py POP (0.60 mmol/g) at room temperature. Such enhancement observed in poly(TPM-BZ-Py) POP was proposed to be caused by the formation of phenolic units and Mannich bridges within the polymer network by taking into consideration the structural transformation during the ring-opening polymerization (ROP). The functionalities in poly(TPM-BZ-Py) have great potential to interact with CO2 molecules through strong intermolecular hydrogen bonding or acid/base interactions, which further supports the benefit of incorporating oxazine rings into POP frameworks.

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.

Simultaneous Dehalogenation and Hydrogenation in Sonogashira Coupling.

We herein report a simultaneous dehalogenation and hydrogenation (DHH) reaction in Sonogashira coupling involving hexahalogenobenzene C6X6 (X = I, Br), in which a halogen on the aryl polyhalide substrate was substituted by a hydrogen atom. First, a steric bulky terminal alkyne 5 was designed and synthesized to study the influence of the reaction conditions (e.g., catalyst, solvent, temperature) and the halogens on the substrates C6X6 on the DHH reaction. Moreover, based on the optimized conditions, a terminal alkyne 6 with less steric hindrance was further synthesized to investigate the influence of alkyne on the DHH reaction. As a result, two aromatic polyynes 7 and 8 were obtained in the DHH process, and their photophysical properties were further studied and compared. The influence produced by the alkynes and aryl polyhalides substrate provide insights into Sonogashira coupling involving terminal alkyne with huge steric hindrance and polyhalogenated aromatic hydrocarbons.

Efficient Synthesis and Microwave‐Assisted Sonogashira Reactions of Triflate‐Substituted Porphyrin

AbstractPorphyrins that bear halogens at the meso‐aryl positions are useful building blocks for the preparation of light‐harvesting arrays and materials through cross‐coupling procedures. Despite the wide use of such intermediates, their scale‐up and purification are usually hampered by tedious chromatographic separations because of the statistical nature of the synthetic protocol and the similar polarity of the different products. Here, we propose the use of porphyrins bearing a triflatophenyl group as alternative starting materials for palladium cross‐coupling reactions. In particular, purification of the zinc 5,10,15‐triaryl‐20‐(4‐triflatophenyl)porphyrin (ZnP‐OTf) model compound by column chromatography proved to be much easier compared to porphyrin analogues that carry halogen substituents. This is the result of the increased polarity of compounds functionalized by highly polar triflate groups if compared to those substituted by halogens. To show the value of the triflatophenylporphyrin model compound in cross‐coupling reactions, we developed a microwave‐assisted Sonogashira protocol that quantitatively converts the ZnP‐OTf to the corresponding alkynylphenylporphyrin, in relatively short reaction times. Finally, we showed that the proposed ZnP‐OTf building block can be conveniently converted into an alkynyl‐linked molecular wire to bridge the zinc porphyrin donor with the [60]fullerene acceptor in a molecular dyad. The prepared dyad showed efficient photoinduced charge separation from singlet ZnP excited state to [60]fullerene in a polar solvent.

Preparation of magnetic biochar functionalized by polyvinyl imidazole and palladium nanoparticles for the catalysis of nitroarenes hydrogenation and Sonogashira reaction

Catalysts are essential materials in biotechnology, medicine, industry, and chemistry. On the other hand, recycling and using waste materials is important in economic efficiency and green chemistry. Thus, biochar was prepared from the stem and roots of the Spear Thistle to recover waste. After magnetizing the biochar, its surface was modified with polyvinyl imidazole. Finally, this modified biochar was decorated with Pd nanoparticles and used as a selective and recyclable nanocatalyst in the hydrogenation of nitroarenes and the Sonogashira reaction. The structure of this organic–inorganic nanocatalyst has been characterized by FESEM-EDS, XRD, FT-IR, TEM, and VSM techniques. In the hydrogenation reaction with the amount of 30 mg of nanocatalyst, the temperature of 50 °C in the water solvent, the reaction efficiency reached 99% for 30 min. In addition, under optimal conditions for the Sonogashira reaction: 1.0 mmol iodobenzene, 1.2 mmol phenylacetylene, 20 mg MBC-PVIm/Pd, 2 mmol K2CO3 in H2O at 50 C for 15 min, the reaction efficiency reached 95%. The recyclability of magnetic nanocatalysts was investigated and recognized this nanocatalyst can be used several times without notable loss of its activity.

Post-synthetic nucleobase modification of oligonucleotides by Sonogashira coupling and influence of alkynyl modifications on the duplex-forming ability.

Recently, we reported that the alkynyl modification of nucleobases mitigates the toxicity of antisense oligonucleotides (ASO) while maintaining the efficacy. However, the general effect of alkynyl modifications on the duplex-forming ability of oligonucleotides (ONs) is unclear. In this study, post-synthetic nucleobase modification by Sonogashira coupling in aqueous medium was carried out to efficiently evaluate the physiological properties of various ONs with alkynyl-modified nucleobases. Although several undesired reactions, including nucleobase cyclization, were observed, various types of alkynyl-modified ONs were successfully obtained via Sonogashira coupling of ONs containing iodinated nucleobases. Evaluation of the stability of the duplex formed by the synthesized alkynyl-modified ONs showed that the alkynyl modification of pyrimidine was less tolerated than that of purine, although both the modifications occurred in the major groove of the duplex. These results can be attributed to the bond angle of the alkyne on the pyrimidine and the close proximity of the alkynyl substituents to the phosphodiester backbone. The synthetic method developed in this study may contribute to the screening of the optimal chemical modification of ASO because various alkynyl-modified ONs that are effective in reducing the toxicity of ASO can be easily synthesized by this method.