Copper-free Sonogashira Cross-coupling Research Articles

Heterogeneous Copper-Free Sonogashira Cross-Coupling Reactions Catalyzed by a Recyclable Orthopalladated Azo-Complex

Heterogeneous Copper-Free Sonogashira Cross-Coupling Reactions Catalyzed by a Recyclable Orthopalladated Azo-Complex

Copper-free Sonogashira cross-coupling reactions: an overview.

The Sonogashira reaction is a cross-coupling reaction of a vinyl or aryl halide with a terminal alkyne to form a C–C bond. In its original form, the Sonogashira reaction is performed with a palladium species as a catalyst while co-catalyzed by a copper species and a phosphine or amine. The reaction is conducted under mild conditions, i.e., room temperature, aqueous solutions, and the presence of mild bases. Undeniably, the Sonogashira reaction is among the most competent and efficient reactions widely used in organic synthesis. This named reaction has proved useful in many organic synthesis areas, including the synthesis of pharmaceuticals, heterocycles, natural products, organic compounds, complex molecules having biological activities, nanomaterials, and many more materials that we use in our daily lives. The presence of transition metals as a catalyst was indeed essential in the Sonogashira reaction. However, recently, the reaction has been successfully conducted without copper as a co-catalyst and phosphines or amines as bases. In this critical review, we have focused on developments in the Sonogashira reaction successfully performed in the absence of copper complexes, phosphines or amines, which could be of particular advantage in implementing green chemistry principles and making the reactions more achievable from an economic viewpoint.

Crystal structure of 1-ferrocenyl-2-(4-nitro-phen-yl)ethyne.

The title ferrocene derivative, [Fe(C5H5)2(C8NO2)], including an alkyne bonded to a para-nitro-phenyl substituent, which was synthesized from a copper-free Sonogashira cross-coupling reaction between ethynylferrocene and 4-bromo-1-nitro-benzene, crystallizes in the P21/n space group. In the ferrocene unit, the penta-dienyl (Cps) rings are in an eclipsed conformation. The angle of rotation between the substituted cyclo-penta-dienyl ring and the p-nitro-phenyl group is 6.19 (10)°, yielding a quasi-linear extension of the ferrocenyl substitution. Important inter-molecular inter-actions arise from π-π stacking between the Cp rings and the p-nitro-phenyl, from corners of the Cp rings that are perpendicularly aligned, and between the O atoms from the nitro substituent and carbons at the corners of the Cp rings, propagating along all three crystallographic axes.

Fundamental Study on Arsenic(III) Halides (AsX3; X = Br, I) toward the Construction of C3-Symmetrical Monodentate Arsenic Ligands.

Arsenic ligands have attracted considerable attention in coordination chemistry. Arsenic(III) halides are the most important starting materials in the preparation of monodentate arsenic ligands. In this work, we optimized the synthetic methodologies of arsenic(III) halides (AsX3; X = Br, I) and examined the difference of their physical properties such as solubility to organic solvent and reactivity to nucleophiles. In addition, a wide variety of monodentate arsenic ligands were prepared with the obtained AsX3. Finally, the obtained monodentate arsenic ligands were utilized for copper-free Sonogashira cross-coupling reaction in the reaction system with porphyrin. The results showed that monodentate arsenic ligands have higher catalytic activity compared with triphenylphosphine because of the difference of the electronic features of lone pairs between arsenic and phosphorus atoms.

Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

The seminal contributions by Sonogashira, Cassar and Heck in mid 1970s on Pd/Cu- and Pd-catalysed (copper-free) coupling of acetylenes with aryl or vinyl halides have evolved in myriad applications. Despite the enormous success both in academia and in industry, however, critical mechanistic questions of this cross-coupling process remain unresolved. In this study, experimental evidence and computational support is provided for the mechanism of copper-free Sonogashira cross-coupling reaction. In contrast to the consensus monometallic mechanism, the revealed pathway proceeds through a tandem Pd/Pd cycle linked via a multistep transmetallation process. This cycle is virtually identical to the Pd/Cu tandem mechanism of copper co-catalysed Sonogashira cross-couplings, but the role of CuI is played by a set of PdII species. Phosphine dissociation from the square-planar reactants to form transient three-coordinate Pd species initiates transmetallation and represents the rate-determining step of the process.

Recyclable supported Pd-NHC catalytic systems for the copper-free Sonogashira cross-coupling in flow

A new family of well-defined NHC-Pd complexes immobilised onto silica, alumina and titania is reported. The catalysts display activity and recyclability in the Sonogashira cross-coupling reactions under batch and continuous flow conditions. Under batch conditions the new catalytic systems were recycled up to four times with yields over 80%. These catalysts have a broad substrate scope of different aryl bromides and alkynes. The titania-supported catalysts show good conversions under continuous flow conditions at least over 8 h on stream using MeOH as solvent.

Palladium(II) Chloride Complexes of N,N'-Disubstituted Imidazole-2-thiones: Syntheses, Structures, and Catalytic Performances in Suzuki-Miyaura and Sonogashira Coupling Reactions.

Reactions of PdCl2 with 2 equiv of N,N'-disubstituted-imidazole-2-thiones R1R2C3N2S (R1 = R2 = Me (1a), iPr (1b), Cy (1c), C6Me3H2 (1d); R1 = Me, R2 = Ph (1e)) under the different conditions afford five mononuclear complexes trans-[(R1R2C3N2S)2PdCl2] (R1 = R2 = Me (2a), iPr (2b), Cy (2c), C6Me3H2 (2d); R1 = Me, R2 = Ph (2e)) and five binuclear Pd(II) complexes [(PdCl2){μ-(R1R2C3N2S)}]2 (R1 = R2 = Me (3a), iPr (3b), Cy (3c), C6Me3H2 (3d); R1 = Me, R2 = Ph (3e)), respectively. Complexes 2a-2e are easily converted into the corresponding 3a-3e by adding equimolar PdCl2 in refluxing MeOH, while the reverse reaction is achieved at room temperature by addition of 2 equiv of 1a-1e. In 2b, 2d, and 2e, each Pd(II) holds a distorted square planar geometry completed by two trans Cl atoms and two trans S atoms. Complexes 3a-3e have a dimeric [Pd2S2] structure in which two {PdCl2} units are interlinked by two N,N'-disubstituted-imidazole-2-thiones. Each Pd(II) adopts a distorted square planar geometry accomplished by two cis Cl atoms and two cis bridging S atoms. Among them, complex 3d has the two largest C6Me3H2 groups on the 2 and 5 positions of imidazole-2-thione, the longest Pd-μ-S bond, the largest S-Pd-S angle, and displays the highest catalytic activity toward Suzuki-Miyaura and copper-free Sonogashira cross-coupling reactions, which are confirmed by density functional theory calculations. The results provide an interesting insight into the introduction of various substituent groups into the periphery ligands of coordination complex-based catalysts, which could tune their geometric structures to acquire the best catalytic activity toward organic reactions.

Palladium Nanoparticles Immobilized on Individual Calcium Carbonate Plates Derived from Mussel Shell Waste: An Ecofriendly Catalyst for the Copper-Free Sonogashira Coupling Reaction.

The conversion of waste into high-value materials is considered an important sustainability strategy in modern chemical industries. A large volume of shell waste is generated globally from mussel cultivation. In this work, mussel shell waste (Perna viridis) is transformed into individual calcium carbonate plates (ICCPs) and is applied as a support for a heterogeneous catalyst. Palladium nanoparticles (3-6 nm) are deposited with an even dispersion on the ICCP surface, as demonstrated by X-ray diffraction and scanning electron microscopy. Using this system, Sonogashira cross-coupling reactions between aryl iodides and terminal acetylenes were accomplished in high yields with the use of 1 % Pd/ICCP in the presence of potassium carbonate without the use of any copper metal or external ligand. The Pd/ICCP catalyst could also be reused up to three times and activity over 90 % was maintained with negligible Pd-metal leaching. This work demonstrates that mussel shell waste can be used as an inexpensive and effective support for metal catalysts in coupling reactions, as demonstrated by the successful performance of the Pd-catalyzed, copper-free Sonogashira cross-coupling process.

Sustainable Approach to Waste-Minimized Sonogashira Cross-Coupling Reaction Based on Recoverable/Reusable Heterogeneous Catalytic/Base System and Acetonitrile Azeotrope

In this contribution, we present a chemically efficient and sustainable protocol for the palladium-catalyzed copper-free Sonogashira cross-coupling reaction, based on the use of a heterogeneous catalytic system. This consists in the combination of a palladium catalyst on highly cross-linked thiazolidine network on silica and a polystyrene-supported base. The solid catalyst/base system acts as a palladium scavenger avoiding leaching of the metal and consequent product contamination. The reaction can be conducted in safe and easily recoverable acetonitrile/water azeotrope as reaction medium. This proved to be an efficient greener alternative to the classic toxic aprotic media commonly used in cross-coupling reaction, such as DMF and NMP. Acetonitrile/water azeotrope could be easily recovered and reused allowing the minimization of waste production. Our approach, based on the use of both a supported base and a supported catalyst, has proven to be efficient for the waste reduction, as proved by the low E-fact...

Synthesis of a novel building block for the preparation of multi-chromophoric sensitizers for panchromatic dye-sensitized solar cells

A simple 3-step synthesis of a novel pyrazine-containing heteroaromatic building block for use as a scaffold for producing multi-chromophoric sensitizers for use in dye sensitized solar cells has been developed. This moiety features two esterified carboxylic acid groups whose hydrolysis provides moieties for anchoring to nanoparticulate metal oxides and two bromine atoms that facilitate attachment of chromophores via palladium mediated cross-coupling methods. The utility of the building block for the synthesis of complex dye motifs is demonstrated by the preparation of a novel panchromatic dye featuring a BODIPY chromophore and a strongly electron donating porphyrin chromophore using both Suzuki and copper-free Sonogashira cross-coupling methods. The building block could be used either to attach two different or identical dye moieties to the metal oxide, or to attach an electron injection dye plus an auxiliary absorber, photoprotective agent, secondary redox moiety, etc.

ONO pincer type binuclear Pd(II) complex: Synthesis, crystal structure and catalytic utilization of the resulting organopalladium complex in catalytic copper-free Sonogashira coupling reaction

New binuclear palladium (II) complex featuring ONO pincer type hydrazone ligand was synthesized and characterized by spectroscopic and single-crystal XRD analysis. This complex showed excellent catalytic activity towards the copper-free Sonogashira cross coupling reaction. The main advantages over previous methodologies include low catalyst loading, less problematic reaction media (H2O–DMSO) and reusability in homogenous systems for optimal performance.

Mechanistic Insights and Implications of Dearomative Rearrangement in Copper-Free Sonogashira Cross-Coupling Catalyzed by Pd-Cy*Phine

The reaction mechanism for the in situ prepared Pd-Cy*Phine catalyst used in copper-free Sonogashira coupling was investigated using density functional theory. In addition, the significance of the meta-terarylphosphine ligand architecture of Cy*Phine was probed, as it had been previously shown experimentally to augment catalytic activity relative to its biarylphosphine analogue, XPhos. The calculated reaction barriers and free energies for the steps in the catalytic cycle suggest that the suppression of a dearomative rearrangement pathway is likely to be an important feature for the improved catalytic performance observed for the Pd-Cy*Phine system.

Synthesis and characterization of functionalized titania-supported Pd catalyst deriving from new orthopalladated complex of benzophenone imine: catalytic activity in the copper-free Sonogashira cross-coupling reactions at low palladium loadings

Efficient catalytic activity of TiO2-supported Pd catalyst in the copper, amine and phosphine free Sonogashira cross-coupling reactions at low Pd-loadings.

Application of palladium complexes bearing acyclic amino(hydrazido)carbene ligands as catalysts for copper-free Sonogashira cross-coupling

Metal-mediated coupling of one isocyanide in cis-[PdCl2(CNR1)2] (R1=C6H11 (Cy) 1, tBu 2, 2,6-Me2C6H3 (Xyl) 3, 2-Cl-6-MeC6H34) and various carbohydrazides R2CONHNH2 [R2=Ph 5, 4-ClC6H46, 3-NO2C6H47, 4-NO2C6H48, 4-CH3C6H49, 3,4-(MeO)2C6H310, naphth-1-yl 11, fur-2-yl 12, 4-NO2C6H4CH213, Cy 14, 1-(4-fluorophenyl)-5-oxopyrrolidine-3-yl 15, (pyrrolidin-1-yl)C(O) 16, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propane-1-yl 17, EtNHC(O) 18] or sulfohydrazides R3SO2NHNH2 [R3=Ph 19, 4-MeC6H420] led to a series of (hydrazido)(amino)carbene complexes cis-[PdCl2{C(NHNHX)N(H)R1}(CNR1)]; X=COR2, SO2R3(21–48, isolated yields 60–96%). All prepared species were characterized by elemental analyses (C, H, N), HR ESI+-MS, IR, 1H and 13C{1H} NMR spectroscopy, and by a single-crystal X-ray diffraction for 38. Complexes 21–48 demonstrated excellent activity as catalysts in copper-free Sonogashira coupling of aryl iodides and a variety of aromatic terminal alkynes. Catalytic system runs in environmentally benign EtOH ensuring product yields of up to 75–96% and TONs of up to 104. Mechanism of the copper-free Sonogashira catalytic cycle involving 21–48 as catalysts was proposed upon identification of key intermediates using HRESI-mass.

Palladium particles from oxime-derived palladacycle supported on Fe3O4/oleic acid as a catalyst for the copper-free Sonogashira cross-coupling reaction

An oxime-derived palladacycle was synthesized using 4-bromobenzoxime and pyridine in CHCl3, and characterized by FT-IR and 1H NMR spectroscopy. This Pd complex was supported on Fe3O4/oleic acid and shown to be an efficient catalyst for the copper-free Sonogashira cross-coupling reaction of various aryl halides with phenylacetylene in air and in ethanol or mixed aqueous medium. The oxime-derived palladacycle gave highly active palladium nanoparticles for the organic synthesis. The coupling products were obtained in high yields with low Pd loading and the heterogeneous catalyst can be separated by an external magnet and reused six times without loss of its activity. The characterization of the catalyst was carried out by XRD, SEM and TEM. Both TEM and XRD revealed that the palladium nanoparticles were well dispersed with diameters from 5 to 10 nm and average size 9.97 nm.

PEG Click‐Triazole Palladacycle: An Efficient Precatalyst for Palladium‐Catalyzed Suzuki‐Miyaura and Copper‐free Sonogashira Reactions in Neat Water

AbstractA novel water‐soluble, phosphine‐free PEG "click" triazole palladacycle has been successfully synthesized. As a precatalyst, the palladacycle exhibited superior catalytic activity towards Suzuki‐Miyaura and copper‐free Sonogashira cross‐coupling in neat water with the turnover numbers (TONs) of up to 9.8×105. In addition, the catalyst could be reused at least 3 times without significant loss of reactivity.

Palladium precatalysts containing meta-terarylphosphine ligands for expedient copper-free Sonogashira cross-coupling reactions

Novel precatalysts containing meta-terarylphosphine ligands have set a new standard for high performance and practicality in copper-free Sonogashira cross-coupling catalysis using simple and reliable protocols.

Palladium Nanoparticles Supported on Poly(N-vinylpyrrolidone)-Grafted Silica as an Efficient Catalyst for Copper-Free Sonogashira and Suzuki Cross-Coupling Reactions

Palladium catalyst based on polyvinylpyrrolidone-silica hybrid support was prepared and exhibited excellent activity and stability in copper, amine and phosphine-free Sonogashira-Hagihara and Suzuki-Miyaura cross-coupling reactions. The polymeric catalyst was applied efficiently in the coupling reactions of chloro (as well as iodo) and bromoarenes. Elemental analysis of Pd by inductively coupled plasma (ICP) and hot filtration test revealed low leaching of the metal into solution from the supported system. The catalyst could be reused many times in repeated cycles without significant decline in its activity.

Copper-free Sonogashira cross-coupling reactions catalyzed by an efficient dimeric C,N-palladacycle in DMF/H$_{2}$O

Very small concentrations of a dimeric C,N-palladacycle were used as an efficient homogeneous catalyst for Sonogashira cross-coupling reactions between various aryl halides and phenylacetylene. The catalytic reactions were performed without the need for copper in DMF/H$_{2}$O. This catalytic system shows excellent yields for aryl iodides and bromides and even in the case of aryl chlorides. \vs{1mm}

A tyrosine-rich peptide induced flower-like palladium nanostructure and its catalytic activity

​Flower-like palladium nanostructure (Pd nano-flower) induced by tyrosine-rich peptide, Tyr-Tyr-Ala-His-Ala-Tyr-Tyr (YYAHAYY), showed excellent catalytic activities in copper-free Sonogashira cross-coupling reaction in water.