Sonogashira Coupling Research Articles

Catalytic Benefits of an Ethynylphenyl-Based PdII Bis(NHC) over a Phenyl-Based PdII Bis(NHC): Insights into the Structural Aspects and Donor Strength Probing.

The amount of cooperation between the metal centers by tailored ligand design is vital to achieve the multimetallic catalytic benefits. Herein, a bimetallic PdII NHC/pyridine complex is synthesized utilizing a novel extended C2-symmetric bis-NHC ligand featuring 1,4-disubstituted ethynylbenzene as a central ligand platform. The complex was further employed for the preparation of a dinuclear complex possessing a combination of NHC and PPh3 ligands. Dinuclear complexes have also been synthesized using a 1,4-di(NHC)-substituted parent benzene ring platform with no acetylene linker units. The donor strengths of both bis-NHC ligands were compared with the help of 13C and 31P chemical shift values as probes. All of the bimetallic complexes were tested as precatalysts in the intermolecular α-arylation of 1-methyl-2-oxindole and Sonogashira coupling reactions. The dinuclear PdII complexes with the ethynylbenzene-bridged bis-NHC ligand showed impressive catalytic outcomes that outweigh the catalytic outcomes obtained with dinuclear bis-NHC complexes possessing no such acetylene linkers. The corresponding mononuclear PdII complexes were synthesized for comparison purposes utilizing both types of central ligand platforms. The dinuclear complexes appeared more active than the corresponding mononuclear complexes in catalysis. Furthermore, higher cooperative index values were obtained in catalysis using the dinuclear PdII complexes with an acetylene-bridged bis-NHC ligand compared to those with no such acetylene linkers.

Hollow microporous organic network fiber membrane for efficient extraction of okadaic acid from marine organisms

Membrane-based micro-solid phase extraction (M-μSPE) has garnered great attention in sample pretreatment, suffering an inherent contradiction between permeability and adsorption capacity. In this study, a pure microporous organic network (TEB-DIB-MON) fiber membrane was prepared by combining electrostatic spinning technology, Sonogashira-Hagihara reaction and template sacrifice method. The prepared TEB-DIB-MON membrane exhibited a large specific surface area with a hollow and porous structure, thereby providing excellent solvent permeability and high adsorption capacity for okadaic acid (OA, an algal toxin). Under the optimized conditions, a sensitive analytical method was established by coupling M-μSPE with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The established method has a low detection limit (0.5 pg mL-1), a wide linear range (1.5-1000 pg mL-1, R ≥ 0.9991), and good reproducibility (RSD ≤ 9.4 %, n = 6), which was then successfully applied for OA detection in marine organisms. Trace amounts of OA (59.3-89.0 pg mL-1) was detected in the oyster and prawn samples. This work demonstrated that the excellent application potential of MON membranes in sample pretreatment, while also presents a novel synthesis strategy for MONs membranes.

Copper Catalysts Anchored on Cysteine-Functionalized Polydopamine-Coated Magnetite Particles: A Versatile Platform for Enhanced Coupling Reactions.

Cysteine plays a crucial role in the development of an efficient copper-catalyst system, where its thiol group serves as a strong anchoring site for metal coordination. By immobilizing copper onto cysteine-modified, polydopamine-coated magnetite particles, this advanced catalytic platform exhibits exceptional stability and catalytic activity. Chemical modification of the polydopamine (PDA) surface with cysteine enhances copper salt immobilization, leading to the formation of the Fe3O4@PDA-Cys@Cu platform. This system was evaluated in palladium-free, copper-catalyzed Sonogashira coupling reactions, effectively catalyzing the coupling of terminal acetylenes with aryl halides. Additionally, the Fe3O4@PDA-Cys@Cu platform was employed in click reactions, confirming the enhanced catalytic efficiency due to increased copper content. The reusability of the platform was further investigated, demonstrating improved performance, especially in recyclability tests in click reaction, making it a promising candidate for sustainable heterogeneous catalysis.

Exploring C2 and N6 Substituent Effects on Truncated 4'-Thioadenosine Derivatives as Dual A2A and A3 Adenosine Receptor Ligands.

Based on high binding affinity of truncated 2-hexynyl-4'-thioadenosine (3a) at both A2A adenosine receptor (AR) and A3 AR, we explored structure-activity relationship (SAR) of the C2-substitution by altering chain length of the 2-hexynyl moiety, thereby evaluating the hydrophobic pocket size. A series of truncated N6-substituted 4'-thioadenosine derivatives with C2-alkynyl substitution were successfully synthesized from D-mannose, using a palladium-catalyzed Sonogashira coupling reaction as the key step, whose structures were confirmed by the X-ray crystal structure of 4h. As the size of the alkynyl group at the C2-position increased, the binding affinity improved; however, when the substituted group was larger than hexynyl, the binding affinity decreased. The introduction of a bulky hydrophobic group such as 3-halobenzyl group at the free N6-amino group decreased the binding affinity at hA2AAR. These results confirm our previous findings that a free amino group at N6-position and longer hydrophobic chain at C2-position are essential for hA2A AR binding affinity. The introduction of a bulky hydrophobic group at free N6-amino group maintained the binding affinity at hA3 AR. The binding mode of truncated 2-substituted-4'-thioadenosine derivatives to hA2A and hA3 AR were predicted by a molecular docking study.

The Cross-selectivity in Pd-catalyzed coupling of simple aryl C-H bonds

Abstract Pd-catalyzed cross-couplings of C-H bonds have been pursued by researchers to produce unsymmetrical C-C bonds directly for over fifty years, which are currently prepared by Suzuki, Kumada, Stille, Neigishi, Heck, or Sonogashira coupling of C-halogen with C-M or C-H bonds. A big challenge is to obtain the high cross-selectivity of cross-coupling products, especially when the substrates have similar chemical C-H bonds, such as simple arenes. Lu and co-workers have studied Pd catalysis in the cross-couplings of aryl C-H bonds since 2003. This account introduces their strategy, understanding and research in cross-selectivity control, C-H activation mode, cross-coupling establishment and application in synthesis. 1 Introduction 2 Cross-selectivity Control 3 Conclusion

Total Synthesis of Tagitinins, Goyazensolide and Related Furanoheliangolides and their Covalent Interaction with Importin‐5 (IPO5)

Herein, we detail an extension of our research on the synthesis of a small library of furanoheliangolides and the characterization of the covalent interaction between goyazensolide and IPO5. Using a build‐couple‐pair strategy, we assembled a small library of germacrene‐type lactones and diversified them into eight groups of structurally different analogues. The germacrene lactones were synthesized using Sonogashira coupling and Barbier‐type macrocyclization, while the furanoheliangolides were further elaborated through gold‐catalyzed transannulation followed by esterification. This synthetic approach enabled the generation of a goyazensolide alkyne‐tagged cellular probe, which was used to identify the selective binding between goyazensolide and the oncoprotein importin‐5 (IPO5). Mass spectrometry analysis of the proteolytic digest from the reaction between the goyazensolide probe and a recombinant IPO5 indicated a covalent engagement at Cys560 of IPO5, which was confirmed by site‐directed mutagenesis.

Halogenase-Assisted Alkyne/Aryl Bromide Sonogashira Coupling for Ribosomally Synthesized Peptides.

We describe the enzymatic bromination of ribosomally synthesized peptides and develop protocols for Sonogashira coupling of peptidic aryl bromides with a panel of alkynes. Using this workflow, entirely new chemical handles are introduced onto ribosomal peptides, including but not limited to terminal alkynes, which enable further diversification via alkyne-azide click chemistry. Regiospecific enzymatic installation of the aryl bromide circumvents genetic code expansion and passivation of other reactive handles on the peptide chain, representing the applicability of biocatalysts in peptide modification chemistry.

Synthetic Approaches to and Structures of Diplatinum Polyynediyl Complexes trans,trans‐[(C6F5)(R3P)2Pt(C≡C)nPt(PR3)2(C6F5)] With Odd Numbers of Triple Bonds; Avoiding Complicating Ethynediyl Extrusions

AbstractReactions of trans‐(C6F5)(p‐tol3P)2Pt(C≡C)nSiEt3 (PtC2nSi; n=5, 7, 9) and excess PtCl in the presence of wet n‐Bu4N+ F− (to effect protodesilylation) under Sonogashira‐type conditions (CuCl, base, other additives) afford the title compounds PtC10Pt, PtC14Pt, and PtC18Pt in 42–32 % yields. A four‐fold substitution of the phosphine ligands in PtC10Pt by PEt3 affords Pt'C10Pt’ (78 %), and a Sonogashira reaction of Pt'C2H and Pt'Cl affords Pt'C2Pt’ (68 %). The analogous reaction with PtC2Si and PtCl is unsuccessful, presumably for steric reasons. The crystal structures of PtC10Pt, PtC14Pt, Pt'C10Pt′, and Pt'C2Pt’ exhibit a number of interesting trends and features. Certain sp chain extension reactions that lead to or employ the precursors PtC10Si, PtC12Si, PtC14Si, and PtC18Si sometimes give byproducts derived from C2 loss, and possible origins are discussed. Related phenomena have been reported by others in the course of synthesizing extended conjugated polyynes.

The Effect of Molecular Structure on the Properties of Fluorene Derivatives for OLED Applications.

A new family of symmetrical fluorene derivatives with different types of substituents attached to the C-2 and C-7 positions of the fluorene core synthesized by the Sonogashira coupling reactions is reported. The electronic structures and the properties of the compounds investigated by means of photoelectron emission spectroscopy, UV-Vis absorption and photoluminescent spectroscopy as well as by DFT and TD-DFT theoretical calculations are discussed. It is shown that the nature of substituents influences the π-conjugation of the molecules. No intermolecular charge transfer within the investigated wavelength range is observed. The applicability of the synthesized compounds in organic light-emitting diodes (OLEDs) based on exciplex emission is demonstrated. The advanced co-deposition technique with the tuned OLED architecture was applied and resulted in improved OLED parameters.

Tetraarylpyrrolo[3,2-b]pyrrole-BODIPY dyad: a molecular rotor for FRET-based viscosity sensing.

With the aim to develop a FRET-based viscosity sensor, two dyad molecules, 4 and 5, comprising tetraarylpyrrolo[3,2-b]pyrrole (TAPP) (donor) and naked boron-dipyrromethene (BODIPY) dyes (acceptor), were designed. Dyads were synthesized via acid-catalyzed multicomponent reactions followed by Sonogashira coupling. In both dyads, the BODIPY and TAPP moieties are linked through phenylethynyl groups, which allow free rotation of the BODIPY dyes; that is, they can act as molecular rotors. This was supported by X-ray crystallographic and DFT-optimized structures. Spectroscopic studies also confirmed the presence of both TAPP and BODIPY dyes in dyads with no electronic interactions that are suitable for fluorescence resonance energy transfer (FRET). Very high energy transfer efficiency (ETE >99%) from the donor TAPP moiety to the acceptor BODIPY moiety on excitation at the TAPP part was observed. However, due to the non-fluorescent nature of naked BODIPY dyes, no fluorescence emission was observed from the BODIPY moiety in both dyads. With increasing solvent viscosities, emission from the BODIPY moieties increases due to the restricted rotation of the BODIPY moieties. Plotting the logarithms of the fluorescent intensity of dyad 5 and the viscosity of the solution showed a good linear correlation obeying a Förster-Hoffmann equation. Non-fluorescent dyad 5 in methanol became greenish-yellow fluorescent in a methanol/glycerol (1:1) solvent. Furthermore, with an increase in the temperature of the methanol/glycerol (1:1) system, as the viscosity decreases, the fluorescence also starts decreasing. Thus, dyad 5 is capable of sensing the viscosity of the medium via a FRET-based "Off-On" mechanism. This type of viscosity sensor with a very large pseudo-Stokes shift and increased sensitivity will be useful for advancing chemo-bio sensing and imaging applications.

Synergistic Anticancer Effects by Enhancing the G-Quadruplex Binding of Nickel(II) Salphen Complexes through Coupling with S-Doped Carbon Nanodots.

In recent decades, researchers have focused on developing less toxic and more precise cancer therapies. Carbon nanodots (CDs) are among the most promising technologies due to their high biocompatibility, tunable fluorescence, and ability to facilitate photothermal and photodynamic therapy. This study explores the synthesis and characterization of two CDs conjugated with Salphen metal complexes, namely, CDs-PEG-M1 and CDs-PEG-M2, through Sonogashira coupling. Their interaction with G-quadruplex DNA structures (G4s), motifs largely involved in cancer development, was evaluated using various spectroscopic techniques. The results indicate that CDs-PEG-M1 exhibits greater effectiveness in stabilizing G4 structures compared to the metal complex alone or nonfunctionalized CDs. This enhanced stabilization suggests that CDs-PEG-M1 could reduce the concentration of the metal complex needed for potential antitumor applications, thereby minimizing side effects on nontarget tissues. When tested on breast cancer models (MDA-MB-231 as a triple-negative model and MCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa), the CDs-PEG-M1 conjugate reduced cell viability in a concentration- and time-dependent manner, showing greater potency and selectivity against cancer cells compared to virgin CDs and the free M1 complex. This synergistic anticancer effect, driven by the interaction with G4 structures and reactive oxygen species production, underscores the potential of CDs-PEG-M1 as a targeted nanotheranostic tool.

A comprehensive review: medicinal applications and diverse synthetic strategies of pyrimidine-based compounds leveraging Suzuki and Sonogashira reactions

A comprehensive review: medicinal applications and diverse synthetic strategies of pyrimidine-based compounds leveraging Suzuki and Sonogashira reactions

Hydrogen‐Bonded Cyclic Tetramer Formation of a Pyridylethynylimidazole‐Based Fluorophore

AbstractSupramolecular have promising application prospects owing to their catalytic, self‐healing, and stimulus‐responsive functions. Pyridylethynylimidazole‐based supramolecular synthons with fluorescent properties have been developed. 4‐(2‐Pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives 1 with different substituents at the 4‐ and 5‐positions of the imidazole skeleton were prepared using a step‐by‐step Sonogashira coupling reaction. The fluorescence maxima of phenyl‐ and methoxyphenyl‐substituted derivatives 1a and 1c were independent of solvent polarity. On the other hand, ester‐ and cyano‐substituted 1b and 1d showed bathochromically shifted fluorescence maxima in highly polar solvents. In crystals, the 4‐(2‐pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives formed a supramolecular cyclic tetramer structure via two hydrogen bonds: one was between N─H in imidazole and N in pyridine, and the other was between C─H in imidazole and N in imidazole. Introducing the pyridine ring as a hydrogen bond acceptor, in addition to the imidazole ring, promoted the unique cyclic tetramer structure formation.

Thienothiophene and benzothiadiazole based conjugated donor-acceptor polymers; synthesis, photophysical properties and organic field effect transistor applications

Novel conjugated donor-acceptor (D-A) type polymers (P1-P3) possessing thieno[3,2-b]thiophenes (TT) as donors having different functional groups and 2,1,3-benzothiadiazole (BT) as an acceptor were designed and synthesized via palladium-catalyzed Sonogashira coupling reaction. Their electronic and optical properties were investigated by UV–Vis and fluorescence spectroscopies and cylic voltammetry analysis. Organic field-effect transistor (OFET) of the polymers were fabricated using biodegradable and environmental-friendly khaya gum as a high dielectric layer to investigate their charge transport characteristics were at low voltage. All the polymers displayed a p-type field-effect behaviour, among which alkyl chain (C9H19) substituted P2 exhibited the highest average saturated hole mobility, μsat, 0.086 cm2 V−1 s−1, on/off current ratio, Ion/Ioff = 1.0 × 103, and subthreshold swing, SS, 425 mV dec−1. The results presented in this work corroborate that the three novel TT-BT polymers have promising potential for electronic and optoelectronic applications, in particular, where tunability of the field-effect behaviour is essential for performance.

Synergistic Pd(OAc)2/CuI-catalyzed alkynylation of β-lactam derivative via Sonogashira coupling

Herein, a novel approach of bimetallic Pd(OAc)2/CuI-catalyzed alkynylation of 3-chloroazetidin-2-one (β-lactam derivative) with terminal alkyne via tandem C–C bond activation/Sonogashira-type cross-coupling reaction is developed. This synthesis encompasses a sequence of inert Csp3–X/Csp–H functionalization processes involving the coupling of the C(sp3) adjacent to the 3-chloroazetidin-2-one with the C(sp) of a terminal alkyne. The final analogs are synthesized by means of the indole-benzothiazole Schiff base formation, cyclization of the Schiff base to generate the β-lactam derivative, and Sonogashira coupling to afford a C(sp3)–C(sp) bond. In addition, indole, benzothiazole, and azetidine-2-one have been identified to be highly efficient heterocyclic scaffolds with a range of pharmacological benefits. It encouraged us to discover a hybrid compound that had each of these moieties. Cooperation between two different metals is essential for the successful implementation of this approach. Specifically, the interaction between the Pd and Cu centers in the transmetallation step is depicted through a plausible mechanistic route. The reaction conditions have been optimized by varying catalyst and ligand loadings, bases, temperatures, and solvents. The reaction is highly efficient, yielding alkynylated products in up to 84 % yield with a wide range of substrates and functional group tolerance, thereby serving as a functional model for the Sonogashira coupling reaction.

Efficient Synthesis of Dithieno[3,2‐B:2’,3’‐d]Thiophenes Derivatives with Promising Optoelectronic Properties Via a One‐Pot, Two‐Step Method with Elemental Sulfur

AbstractDithieno[3,2‐b:2’,3’‐d]thiophene (DTT) derivative contains three annulated thiophene rings, which have attracted great attention in the field of materials due to its planar and conjugated molecular, structural rigidity, and increased solubility. Herein, the one‐step modular construction of a series of structurally well‐defined 2,6‐disubstituted dithieno[3,2‐b:2’,3’‐d]thiophenes (2,6‐DTT) involves Pd/Cu(I)‐catalyzed Sonogashira coupling and LiNH2‐mediated ring‐closing reaction with element sulfur was reported. The method allows the selective and straightforward introduction of different aryl substitution into DTT without otherwise tedious separation and purification processes. The preliminary study of the thermal and photophysical properties demonstrated that the introduction of substituent in phenyl has great impact for the parent molecule, which enable this protocol to synthesis high‐performance 2,6‐DTT through the different alkynes.

Enhanced detection of catecholamines in human urine using Cis-diol-microporous organic networks with PT-SPE and HPLC-MS/MS

A novel cis-diol-microporous organic networks (MONs-2OH) material was synthesized via room temperature and Sonogashira coupling reactions, which exhibits exceptional adsorption properties for catecholamines (CAs). MONs-2OH demonstrates robust hydrogen bonding and π-π stacking interactions, crucial for effective adsorption. The MONs-2OH was incorporated into pipette tip solid-phase extraction and developed a new method for detecting CAs in human urine using HPLC-MS/MS. Characterization of the adsorbent revealed its high stability, large specific surface area, abundant phenolic hydroxyl groups, rapid extraction speed, and superior adsorption efficiency. The method achieved a wide linear range (0.5–500 ng/mL), low detection limits (0.06–0.26 ng/mL), high accuracy (90.4 %-99.4 %), and excellent precision (RSD ≤ 10 %). Comparative studies showed MONs-2OH outperforms commercial adsorbents in terms of recovery and adsorption capacity. The results underscore the potential of MONs-2OH for rapid and sensitive CAs determination, offering significant advantages for the auxiliary diagnosis of depression and enhancing the application of PT-SPE in sample pretreatment.

1,2,3-Triazole-Guided Multi-Component Sonogashira Coupling of Substituted Benzosuberenes Derived from Cedrus deodara Oil

AbstractHerein, Sonogashira coupling at the vinyl bromide position of triazole-bearing benzosuberene has been introduced for the synthesis of potentially bioactive 1,2,3-triazole and conjugated enynes containing benzosuberene analogues. The instalment of triazole moiety on the allylic position dictates the Sonogashira coupling at the vinylic position, the absence of which failed to execute the desired reaction. The Cu-catalyzed cycloaddition initially led to the incorporation of 1,2,3-triazole, which subsequently directed the Pd/Cu-catalyzed Sonogashira coupling to deliver new class of benzosuberene analogues in appreciable yields. The regioselective synthesis of 1,2,3-triazole and conjugated enynes containing benzosuberene analogues has been reported under operationally simple and milder reaction conditions.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling.

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling