Substituted Aryl Bromides Research Articles

Ligand-Free Copper(I) Chloride Catalyzed N-Arylation of 1,2,4-Triazole with Aryl Bromides

AbstractAn efficient protocol was developed for the N-arylation of 1,2,4-triazole by using substituted aryl bromides catalyzed by CuCl under ligand-free conditions. This method afforded the products in good to excellent yields (up to 88%) under the optimized conditions.

Copper catalyzed N-arylation of sulfonamides with aryl bromides under ligand-free conditions

A practical strategy for the C-N cross-coupling of both aliphatic and aromatic sulfonamides with a variety of substituted aryl bromides is reported. Under the optimized conditions, a good representative of N-arylated products were obtained in good to excellent yields (up to 78%) under the ligand-free conditions.

A ligand-free copper-catalyzed strategy to the N-arylation of indazole using aryl bromides

A simple and efficient strategy for the C–N cross-coupling of indazole with a variety of substituted aryl bromides is reported. Under the optimized conditions, a broad scope of N-arylated products were obtained in good to excellent yields (up to 87%) under the ligand-free conditions.

CeO2/Pd Nanoparticles Incorporated Fly Ash Zeolite: An Efficient and Recyclable Catalyst for Csp2‐Csp2Bond Formation Reactions

The catalytic activity of CeO2and palladium nanoparticles supported fly ash zeolite (CeO2/Pd@FAZ) for Csp2‐Csp2bond formation was studied. CeO2/Pd@FAZ was characterized by FTIR, XRD, EDAX and TEM studies. In the Suzuki‐Miyauracross‐coupling reaction, biphenyl derivatives with excellent yields were obtained, and the reaction conditions were optimized. The catalytic activity was explored using a wide variety of diversely substituted aryl bromides and chlorides with aryl boronic acid under optimized reaction conditions. The recyclability of the catalyst was established for three cycles, with the conversion rate from 99 to 40%, which gained the advantage of heterogeneous catalysis.

Palladium loaded on ZnO nanoparticles: Synthesis, characterization and application as heterogeneous catalyst for Suzuki–Miyaura cross-coupling reactions under ambient and ligand-free conditions

Pd loaded ZnO nanoparticles have been explored as an efficient catalyst for Suzuki-Miyaura cross-coupling reactions under ambient and ligand-free conditions. For this purpose, the low temperature synthesis of ZnO nanoparticle was accomplished by the solution based approach using stoichiometric amount of zinc acetate and urea. The Pd/ZnO nanocrystalline catalyst was prepared by loading 3% PdCl2 on ZnO nanoparticles by simple wet impregnation technique. This catalyst efficiently performed Suzuki-Miyaura reactions with various ring substituted aryl bromides and boronic acids. The resultant Pd/ZnO nanocrystalline material conferred 97% yield under optimized reaction conditions. The nanostructured Pd loaded ZnO catalyst was characterized by XRD, FESEM, EDS, FETEM, STEM-BF-DF, XPS and BET techniques. XRD pattern of Pd/ZnO sample hints the presence of Pd as minor phase loaded on ZnO nanocrystalline material, while overall XPS analysis discloses effective loading of Pd (0) on ZnO surface. FESEM/TEM–EDS also revealed reasonable Pd loading on ZnO nanoparticles. The FETEM examination of unloaded ZnO and Pd loaded ZnO disclosed particle size in the range 25–40 nm. The nanocrystalline Pd/ZnO catalyst was reused without significant loss of catalytic activity. The present methodology is cost effective, environmentally friendly, easy to scale up and can become an alternative to homogeneous catalysis.

Enantioselective Synthesis of β-Quaternary Carbon-Containing Chromanes and 3,4-Dihydropyrans via Cu-Catalyzed Intramolecular C-O Bond Formation.

A copper-catalyzed efficient enantioselective construction of chiral quaternary carbon-containing chromanes and 3,4-dihydropyrans is reported. The desymmetric C-O coupling is enabled by a chiral dimethylcyclohexane-1,2-diamine ligand and provides the desired products in good yields with high enantioselectivities. This method presents a broad substrate scope and is applicable to diversely substituted aryl bromides and alkenyl bromides. The application is demonstrated by a gram-scale synthesis and derivatization of the products toward valuable building blocks.

Palladium(II) catalyzed Suzuki C[sbnd]C coupling reactions with imino- and amino-phosphine ligands

A new series of bidentate PN type imino- (1–3) and amino-phosphine ligands (4–6) and their palladium(II) complexes [Pd(PN)Cl2] (1a–6a) have been synthesized and fully characterized using spectroscopic and analytical methods, including 31P, 1H, 13C NMR and FTIR spectroscopy and high resolution mass spectroscopy. The catalytic activities of the Pd(II) complexes were investigated for the Suzuki CC coupling reactions of phenylboronic acid with aryl bromides using a substrate to catalyst ratio of 500/1. The effect of base, temperature and solvent has been investigated, and the highest reaction rates were observed at 80 °C in dimethylformamide (DMF) with K2CO3 as the base in 12 h. Under optimized reaction conditions, generally higher coupled product was obtained with substituted aryl bromides, including both electron-withdrawing (-formyl and -aceto) or -donating groups (-methyl and -methoxy) at -ortho or -para positions, except 2-bromoacetophenone which has bulkier -aceto group compared to the other aryl bromides.

Development of a Concise Multikilogram Synthesis of LPA-1 Antagonist BMS-986020 via a Tandem Borylation–Suzuki Procedure

The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commercially available palladium catalyst for both steps. This methodology addressed shortcomings of early synthetic routes and was ultimately used for the multikilogram scale synthesis of the active pharmaceutical ingredient 1. Further evaluation of the borylation reaction showed useful reactivity with a range of substituted aryl bromides and iodides as coupling partners. These findings represent a practical, efficient, mild, and scalable method for borylation.

Synthesis, structure and catalytic applications of octahedral nickel(II) benzoylhydrazone complex: Suzuki–Miyaura cross-coupling reaction of aryl bromides with arylboronic acid

A simple route for the synthesis of a new octahedral nickel(II) complex (1) containing 4-chloro-benzoic acid pyridin-2-ylmethylene-hydrazide ligand (HL, where H represents the dissociable proton) has been described. The characterization of the complex having the formula [Ni(μ3-O,N,N-L)2] has been established by elemental analysis, ESI-MS, spectral methods and single crystal X-ray crystallography. Further, the new complex was found to act as an active homogeneous catalyst for the Suzuki–Miyaura reaction of substituted aryl bromides (mono and dibromides) with various arylboronic acids having different electronic effects under optimized conditions of solvent, base and catalyst loading. The biphenyl and triphenyl derivatives were obtained in moderate to excellent isolated yields.

Copper-catalyzed C–N bond cross-coupling of aryl halides and amines in water in the presence of ligand derived from oxalyl dihydrazide: scope and limitation

An efficient and convenient method has been developed for the copper-catalyzed C–N bond cross-coupling of aryl bromides with electron-donor substituents and aliphatic amines in water. The new ligand system N-phenyloxalyl bishydrazide/hexane-2,5-dione has been shown to be considerably more efficient in the copper-catalyzed C–N bond cross-coupling reaction as compared to the ligands described in the literature and allowed decreasing of the catalyst amount (up to 2 mol%) to achieve acceptable yields of isolated products (46–84%). Acceptor substituted aryl bromides, aryl bromides with substituents in the ortho-position, and some aryl dichlorides can undergo the C–N cross-coupling under the developed conditions, but their reactivity is lower.

New Polysilyl Dendritic Precursors of Triazolylferrocenyl and Triazolylcobalticenium Dendrimers—Comparative Electrochemical Study and Stabilization of Small, Catalytically Active Pd Nanoparticles

The 27-ferrocenyl-terminated and the 27-cobalticenium-terminated metallodendrimers 5 and 6, respectively, were synthesized using only hydrosilylation reactions and click methodology. These new metallodendrimers were characterized by 1H and 13C NMR, infrared, and mass spectroscopy, elemental analysis, and cyclic voltammetry. The dendrimers 5 and 6, being isostructural in their neutral forms, show the same intensities for the redox exchange between their neutral and cationic forms, corresponding approximately to the transfer of 27 electrons, as deduced from the Bard–Anson equation. The metallodendrimer 5 was used to form dendrimer-encapsulated palladium nanoparticles (PdDENs). TEM images indeed show that the PdDENs are very small (average diameter = 1.0 nm) and relatively monodisperse. Their catalytic activity was evaluated for the Suzuki–Miyaura C–C coupling with various substituted aryl bromides (0.2 mol% of Pd per mole of substrate used). This activity is lower than that of previously studied dendrimers ...

Copper/N,N-dimethylglycine catalyzed goldberg reactions between aryl bromides and amides, aryl iodides and secondary acyclic amides.

An efficient and general copper-catalyzed Goldberg reaction at 90–110 °C between aryl bromides and amides providing the desired products in good to excellent yields has been developed using N,N-dimethylglycine as the ligand. The reaction is tolerant toward a wide range of amides and a variety of functional group substituted aryl bromides. In addition, hindered, unreactive aromatic and aliphatic secondary acyclic amides, known to be poor nucleophiles, are efficiently coupled with aryl iodides through this simple and cheap copper/N,N-dimethylglycine catalytic system.

Palladium Nanoparticles Stabilized by Glycodendrimers and Their Application in Catalysis

AbstractPalladium nanoparticles stabilized by glycodendrimers (PdDSNs) in water were prepared by coordination of PdII to intradendritic triazole ligands upon reaction of K2PdCl4 with the dendrimer in water followed by aqueous NaBH4 reduction to Pd0. TEM images show that the PdDSNs are small (average diameter: 2.3 nm) and relatively monodisperse owing to a low concentration of metal precursor. The catalytic activity of these PdDSNs was evaluated for the reduction of 4‐nitrophenol (4‐NP) to 4‐aminophenol (4‐AP) by NaBH4 (only 0.2 mol‐% of Pd per mol substrate is used) and for the Miyaura–Suzuki C–C coupling with various substituted aryl bromides (only 0.01 mol‐% of Pd per mol substrate is used). Comparisons of the catalytic activities of these PdDSNs with those of larger PdDSNs (diameter: 14 nm) reveal that smaller NPs catalyze faster 4‐NP reduction than their larger counterparts but lack any notable surface dependency for Suzuki–Miyaura catalysis.

Palladium‐catalyzed direct arylation of polyfluoroarene and facile synthesis of liquid crystal compounds

A convenient approach has been developed to prepare polyfluorobiphenyl by Pd(OAc)2/PCy3‐catalyzed direct arylation of polyfluoroarenes with aromatic halides in the presence of Cs2CO3 as base and toluene as solvent. In most cases, the desired arylated products of aromatic bromides were obtained in good to excellent yield at 80°C, and aryl chlorides also gave modest to good yields of arylated products at 110°C. According to this efficient C―C bondforming method, polyfluorobiphenyl liquid crystal compounds were prepared by Pd‐catalyzed direct arylation reactions of polyfluoroarenes with long alkyl chain substituted aryl bromides in 62–96% yield. Copyright © 2014 John Wiley & Sons, Ltd.

Polymer supported Pd catalyzed carbonylation of aryl bromides for the synthesis of aryl esters and amides

A new polymer anchored Pd(ii) Schiff base catalyst has been synthesized for the evaluation of alkoxycarbonylation and aminocarbonylation reactions of various substituted aryl bromides with alcohols and amines.

ChemInform Abstract: Phosphine‐Free Palladium‐Catalyzed Direct C2‐Arylation of Benzothiophenes with Aryl Bromides.

AbstractLow loadings of Pd(OAc)2 (0.1‐0.5 mol%) as catalyst are found to promote the direct C2‐arylation of benzothiophenes with a wide range of different substituted aryl bromides.

Palladium supported on silica gel confined ionic liquid as a reusable catalyst for carbon–carbon cross coupling reaction in water

We have developed an efficient method for carbon-carbon cross coupling reactions using a palladium- catalyst supported on porous silica gel confined ionic liquid, 1-decyl-3-methyl imidazolium fluoroborate ((dmim)BF4) in water at 80 C. A variety of substituted aryl bromides underwent Suzuki and Heck coupling with various boronic acids and acrylates respectively to produce a series of functionalized biaryls and cinnamates in high yields. The catalyst is stable, recyclable and it offers very high turnover numbers.

N-Arylation of Protected Azamacrocycles

A rapid method for efficient palladium-catalyzed N-aryl­ation of polynitrogenated macrocycles is presented. Its applicability for functionalization of protected azamacrocycles of various sizes with substituted aryl bromides of optional electronic properties is demonstrated. The compatibility of the protocol with common N-protecting schemes as well as the impact of electronic versus steric factors is discussed. Using a commercially available catalytic system and easily available alkoxide or phenoxide base, the method provides moderate to excellent yields of N-arylated azamacrocycles (45–96%).

Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M]). A Hammett study showed a linear correlation of σ and σ(−) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2–1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents.

On the Mechanism of the Palladium-Catalyzed β-Arylation of Ester Enolates

The palladium-catalyzed β-arylation of ester enolates with aryl bromides was studied both experimentally and computationally. First, the effect of the ligand on the selectivity of the α/β-arylation reactions of ortho- and meta-fluorobromobenzene was described. Selective β-arylation was observed for the reaction of o-fluorobromobenzene with a range of biarylphosphine ligands, whereas α-arylation was predominantly observed with m-fluorobromobenzene for all ligands except DavePhos, which gave an approximate 1:1 mixture of α-/β-arylated products. Next, the effect of the substitution pattern of the aryl bromide reactant was studied with DavePhos as the ligand. We showed that electronic factors played a major role in the α/β-arylation selectivity, with electron-withdrawing substituents favoring β-arylation. Kinetic and deuterium-labeling experiments suggested that the rate-limiting step of β-arylation with DavePhos as the ligand was the palladium-enolate-to-homoenolate isomerization, which occurs by a βH-elimination, olefin-rotation, and olefin-insertion sequence. A dimeric oxidative-addition complex, which was shown to be catalytically competent, was isolated and structurally characterized. A common mechanism for α- and β-arylation was described by DFT calculations. With DavePhos as the ligand, the pathway leading to β-arylation was kinetically favored over the pathway leading to α-arylation, with the palladium-enolate-to-homoenolate isomerization being the rate-limiting step of the β-arylation pathway and the transition state for olefin insertion its highest point. The nature of the rate-limiting step changed with PCy(3) and PtBu(3) ligands, and with the latter, α-arylation became kinetically favored. The trend in selectivity observed experimentally with differently substituted aryl bromides agreed well with that observed from the calculations. The presence of electron-withdrawing groups on these bromides mainly affected the α-arylation pathway by disfavoring C-C reductive elimination. The higher activity of the ligands of the biaryldialkylphosphine ligands compared to their corresponding trialkylphosphines could be attributed to stabilizing interactions between the biaryl backbone of the ligands and the metal center, thereby preventing deactivation of the β-arylation pathway.