Ligand-free Suzuki Miyaura Coupling Research Articles

Synthesis of a 3,7-Disubstituted Isothiazolo[4,3-b]pyridine as a Potential Inhibitor of Cyclin G-Associated Kinase.

Disubstituted isothiazolo[4,3-b]pyridines are known inhibitors of cyclin G-associated kinase. Since 3-substituted-7-aryl-isothiazolo[4,3-b]pyridines remain elusive, a strategy was established to prepare this chemotype, starting from 2,4-dichloro-3-nitropyridine. Selective C-4 arylation using ligand-free Suzuki-Miyaura coupling and palladium-catalyzed aminocarbonylation functioned as key steps in the synthesis. The 3-N-morpholinyl-7-(3,4-dimethoxyphenyl)-isothiazolo[4,3-b]pyridine was completely devoid of GAK affinity, in contrast to its 3,5- and 3,6-disubstituted congeners. Molecular modeling was applied to rationalize its inactivity as a GAK ligand.

Palladium@silica-coated magnetic nanoparticles as efficient and recyclable catalysts for ligand-free Suzuki–Miyaura coupling reaction under mild conditions

Palladium@silica-coated magnetic nanoparticles as efficient and recyclable catalysts for ligand-free Suzuki–Miyaura coupling reaction under mild conditions

Development of Facile and Simple Processes for the Heterogeneous Pd-Catalyzed Ligand-Free Continuous-Flow Suzuki–Miyaura Coupling

The Suzuki–Miyaura coupling reaction is one of the most widely utilized C–C bond forming methods to create (hetero)biaryl scaffolds. The continuous-flow reaction using heterogeneous catalyst-packed cartridges is a practical and efficient synthetic method to replace batch-type reactions. A continuous-flow ligand-free Suzuki–Miyaura coupling reaction of (hetero)aryl iodides, bromides, and chlorides with (hetero)aryl boronic acids was developed using cartridges packed with spherical resin (tertiary amine-based chelate resin: WA30)-supported palladium catalysts (7% Pd/WA30). The void space in the cartridge caused by the spherical catalyst structures enables the smooth flow of a homogeneously dissolved reaction solution that consists of a mixture of organic and aqueous solvents and is delivered by the use of a single syringe pump. Clogging or serious backpressure was not observed.

Nickel(II) Nanoparticles Immobilized on EDTA-Modified Fe3O4@SiO2 Nanospheres as Efficient and Recyclable Catalysts for Ligand-Free Suzuki-Miyaura Coupling of Aryl Carbamates and Sulfamates.

A highly efficient and air-, thermal-, and moisture-stable nickel-based catalyst with excellent magnetic properties supported on silica-coated magnetic Fe3O4 nanoparticles was successfully synthesized. It was well characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, transmission electron microscopy, field emission scanning electron microscopy, thermogravimetric analysis, dynamic light scattering (DLS), X-ray photoelectron spectroscopy, vibration sample magnetometry, energy-dispersive X-ray analysis, inductively coupled plasma analysis, and nitrogen adsorption–desorption isotherm analysis. The Suzuki–Miyaura coupling reaction between aryl carbamates and/or sulfamates with arylboronic acids was selected to demonstrate the catalytic activity and efficiency of the as-prepared magnetic nanocatalyst. Using the mentioned heterogeneous nanocatalyst in such reactions generated corresponding products in good to excellent yields in which the catalyst could easily be recovered from the reaction mixture with an external magnetic field to reuse directly for the next several cycles without significant loss of its activity.

Development of Titanium Dioxide-Supported Pd Catalysts for Ligand-Free Suzuki–Miyaura Coupling of Aryl Chlorides

The catalyst activities of various heterogeneous palladium catalysts supported by anatase-, rutile- and brookite-type titanium oxide for ligand-free Suzuki–Miyaura cross-coupling reactions of aryl chlorides were evaluated. Palladium acetate [Pd(OAc)2], supported on anatase-type titanium oxide (TiO2) via acetonitrile solution impregnation process without reduction [Pd/TiO2 (anatase-type)], demonstrated the highest catalyst activity in comparison to those of other titanium oxide (rutile- or brookite-type) supported Pd(OAc)2 without reduction and reduced Pd/TiO2 (anatase-type) [Pd(red)/TiO2 (anatase-type)]. Various aryl chloride and bromide derivatives were smoothly coupled with arylboronic acids including heteroarylboronic acids in the presence of 5–10 mol% Pd/TiO2 (anatase-type) without the addition of any ligands. Although the fresh Pd/TiO2 (anatase-type) catalyst was surprisingly comprised of ca. 1:2 mixture of palladium(II) and palladium(0) species according to X-ray photoelectron spectroscopy (XPS), in spite of no reduction process, significant further increment of palladium(0) species was observed during the Suzuki–Miyaura coupling reaction, and Pd/TiO2 (anatase-type) was converted into a catalyst, which contained palladium(0) species as the main component [ca. 1:5 mixture of palladium(II) and palladium(0) species]. Therefore, the reduction via the electron donation process to the palladium(II) species may have occurred during the reaction on anatase-type titanium oxide.

Ligand-free Suzuki–Miyaura coupling reaction of an aryl chloride using a continuous irradiation type microwave and a palladium nanoparticle catalyst: effect of a co-existing solid

A co-existing solid, Al foil, plays a key role in ligand-free Suzuki–Miyaura coupling using SGlPd (sulfur-modified glass-supported Pd) and continuous microwave irradiation.

Ligand-free Suzuki–Miyaura coupling using ruthenium(0) nanoparticles and a continuously irradiating microwave system

A good combination between a continuously irradiating microwave system and recyclable Ru(0) nanoparticle for ligand-free Suzuki–Miyaura coupling.

Green synthesis, characterization and catalytic activity of the Pd/TiO2 nanoparticles for the ligand-free Suzuki–Miyaura coupling reaction

A green synthesis process was developed for production of the Pd/TiO2 nanoparticles (NPs) without using toxic, hazardous and dangerous materials. Myrtus communis L. leaf extract serves as a mild, renewable and non-toxic reducing agent. The advantages of this biosynthesis method include use of cheap, clean, nontoxic and environmentally benign precursors and simple procedures without time-consuming polymerization and problems with treatment of a highly viscous polymeric resin. More importantly, the synthesized Pd/TiO2 NPs presented excellent catalytic activity for ligand-free Suzuki–Miyaura coupling which could be easily separated from the reaction mixture and reused many times with no loss of activity. Therefore, these properties indicate demonstrative benefits of the catalyst. The Pd/TiO2 NPs was characterized by FESEM, TEM, FT-IR, UV–vis spectroscopy and EDS.

Graphene oxide supported Au nanoparticles as an efficient catalyst for reduction of nitro compounds and Suzuki–Miyaura coupling in water

This paper reports on the synthesis of graphene oxide supported Au nanoparticles and their application as a separable catalyst for ligand-free Suzuki–Miyaura coupling reactions in water and reduction of nitro compounds. The catalyst was characterized using powder XRD, BET, FT-IR, Raman, SEM and EDS. This method has the advantages of high yields, simple methodology, and elimination of ligand, organic solvent and homogeneous catalysts and easy work up. Interestingly, the novel catalyst could be recovered in a facile manner from the reaction mixture and recycled several times without any significant loss of catalytic activity.

Ligand-Free Suzuki–Miyaura Coupling Reactions Using an Inexpensive Aqueous Palladium Source: A Synthetic and Computational Exercise for the Undergraduate Organic Chemistry Laboratory

An inexpensive procedure for introducing the Suzuki–Miyaura coupling reaction into a high-enrollment undergraduate organic chemistry laboratory course is described. The procedure employs an aqueous palladium solution as the catalyst and a range of para-substituted aryl bromides and arylboronic acids as substrates. The coupling reactions proceed rapidly at room temperature using standard glassware and do not require ligands, an inert atmosphere, or specialized equipment. Computational chemistry is used to explore the molecular and electronic structures of typical starting materials and products of the Suzuki–Miyaura coupling.

Ligand-Free Suzuki–Miyaura Coupling with Sulfur-Modified Gold-Supported Palladium in the Synthesis of a Conformationally-Restricted Cyclopropane Compound Library with Three-Dimensional Diversity

A conformationally restricted privileged structure library with stereochemical diversity for a "fragment growth" methodology comprising 90 compounds was designed and systematically and efficiently synthesized using sulfur-modified Au-supported Pd (SAPd)-catalyzed ligand-free Suzuki-Miyaura coupling of vinyl iodide promoted by microwave and subsequent amidation in liquid-phase combinatorial chemistry as key reactions. Evaluation of the compounds with a 20-kinase panel indicated the usefulness of this "fragment growth" methodology for finding hit library compounds for fragment-based drug discovery.

Ni2O3-around-Pd hybrid on graphene oxide: An efficient catalyst for ligand-free Suzuki–Miyaura coupling reaction

Ni2O3-around-Pd hybrid can be fabricated on graphene oxide (Pd–Ni/RGO) by a simple one-pot wet chemical route. These isolated Pd clusters showed significantly improved performance for Suzuki coupling reaction compared to that of pure Pd/RGO, Ni2O3/RGO, popularly reported Pd/AC, as well as homogeneous PdCl2 and PdCl2(PPh3)2. Characterizations disclosed that Ni2O3 plays multiple roles in exfoliating graphene sheets, mediating the size as well as stability of Pd clusters. Pd–Ni/RGO dispersed homogeneously in the aqueous reaction mixture, exhibited high enrichment towards reactants as well as extremely high activity and stability for the Suzuki coupling reaction. The best turnover frequencies of all Pd atoms reached 38,750h−1 at 80°C for bromobenzene coupling. It was concluded that the intimate interaction between Ni2O3 nanoparticles and Pd clusters appears to be beneficial for activating the Pd surface for the catalytic cycle.

Modified zeolite immobilized palladium for ligand-free Suzuki–Miyaura cross-coupling reaction

A palladium-based catalyst supported on modified ZSM-5 was successfully prepared by a facile procedure. The prepared heterogeneous catalyst Pd@desilicated ZSM-5 showed an excellent catalytic activity at very low Pd loading (0.02 mol%) for the ligand-free Suzuki–Miyaura coupling reactions of various aryl bromides affording excellent yields of the products. The prepared catalyst presents good recyclability, over four catalytic cycles.

An efficient protocol for palladium-catalyzed ligand-free Suzuki–Miyaura coupling in water

An in situ generated catalytic system based on PdCl2 and sodium sulfate exhibited excellent catalytic activity in the Suzuki–Miyaura cross-coupling reactions of aryl halides with arylboronic acids at room temperature in water. A similar catalytic system can be obtained with PdCl2 and sodium chloride or sodium acetate and is equally effective in Suzuki–Miyaura cross-coupling reactions. This method offers a mild and efficient alternative to the existing protocols since the reaction is proceeded in water at room temperature under ligand free conditions.

Heterogeneous Pd/C-catalyzed ligand-free Suzuki–Miyaura coupling reaction using aryl boronic esters

Heterogeneous Pd/C-catalyzed Suzuki–Miyaura cross-coupling reaction of aryl boronic esters with aryl bromides was successfully carried out in aqueous media at room temperature without the use of a ligand such as phosphine derivatives.

Heterogeneous Pd/C‐Catalyzed Ligand‐Free, Room‐Temperature Suzuki–Miyaura Coupling Reactions in Aqueous Media

A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis.

Ligand-free Suzuki–Miyaura reaction catalysed by Pd/C at room temperature

Ligand-free Suzuki–Miyaura coupling reaction has been developed which utilises a commercially available 10% Pd/C (2.6 mol% Pd) in 2-propanol-H2O (1/1) and Na3PO4 at room temperature. The reaction is mild and generates excellent yields of the coupled products (90–100%). The catalyst is heterogeneous and ligand-free, and the product isolation is simple.