Suzuki-type Coupling Reactions Research Articles

A comparative study on Suzuki-type 11 C-methylation of aromatic organoboranes performed in two reaction media.

The Suzuki-type cross coupling reaction is a palladium-mediated multistep reaction that has been used to synthesize several 11 C-labeled tracers for PET. However, the impact of the selected organoborane reagent and reaction medium on the radiochemical yield (RCY) has not been thoroughly investigated. To bridge this gap, we studied the synthesis of 1-[11 C]methylnaphthalene using four different organoborane precursors in reactions performed in DMF/water and THF/water. In the synthesis of 1-[11 C]methylnaphthalene, the best radiochemical yields (RCYs), approximately 50%, were obtained with boronic acid and pinacol ester precursors, whereas less than 4% RCY was obtained when performing the reaction with the N-methylimidodiacetic acid boronic ester (MIDA ester) precursor. 1-[11 C]methylnaphthalene was obtained in higher yields in almost all syntheses performed in THF/water as compared to DMF/water. This observation was in line with previously reported results for [11 C]UCB-J, a tracer for the synaptic vesicle glycoprotein 2A (SV2A) receptor, that also was obtained in higher RCY when synthesized in THF/water. The same trend was observed with [11 C]cetrozole, where the RCY was more than doubled in THF/water compared to the previously published synthesis performed in DMF. These results suggest that THF/water could be the preferred reaction medium when producing PET tracers via the Suzuki-type coupling reaction.

Support-Free Pd3 Co NCs as an Efficient Heterogeneous Nanocatalyst for New Organic Transformations of C-C Coupling Reactions.

A support-free heterogeneous Pd3 Co nanostructured composite (NC), synthesized through a hydrothermal route, acted as an effective catalytic system in multivariate Heck-, Sonogashira-, and Suzuki-type coupling reactions of iodonium ylides. The XPS analysis of the bimetallic Pd3 Co NCs confirmed the elemental composition as 75 % palladium and 25 % cobalt. Furthermore, high-resolution (HR) TEM analysis confirmed the spherical morphology of the Pd3 Co bimetallic nanoparticles. The average diameter of the NCs is 14.8 nm. The coupling reaction proceeded through the generation of α-iodoenones with simultaneous migration of the phenyl group, thereby giving a scaffold with higher atom economy. The heterogeneous Pd3 Co NCs were recycled and reused without any significant change in catalytic ability for up to five reaction cycles. The high concentration of Pd and association of cobalt into the lattice of palladium appears to enhance its catalytic ability for the diverse coupling reactions in comparison with its monometallic counterparts as well as with bimetallic NCs with a comparatively lesser amount of Pd.

Ligand‐Free Cu‐Catalyzed Suzuki Coupling of Alkynyl Bromides with Boronic Acids in Ethanol Under Microwave Irradiation

AbstractA ligand‐free microwave assisted synthesis of internal alkynes using copper‐catalyzed Suzuki type coupling reaction of alkynyl bromides with boronic acid derivatives has been developed. This protocol uses cheap CuI, greener solvent ethanol and K3PO4 base under microwave irradiation. This strategy does not need any ligand or sealed tube conditions. This methodology provides an efficient way to synthesize 1,2‐diarylacetylenes in good to excellent yields.

ChemInform Abstract: A Supramolecular Ensemble of a PBI Derivative and Cu2O NPs: Potential Photocatalysts for the Suzuki and Suzuki Type Coupling Reactions.

AbstractThe aggregates of a perylene bisimide derivative in combination with Benedict′s reagent are used as photocatalyst for the photocatalytic Suzuki‐type coupling reaction of boronic acid/ester with tosyl aziridines and for Suzuki coupling reactions with various aryl halides.

ChemInform Abstract: Synthesis, Characterization, and Application of Palladium‐Dithizone Immobilized on Magnetic Nanoparticles as an Efficient and Recoverable Catalyst for Suzuki Type Coupling Reactions.

A novel, magnetically separable catalyst was synthesized by the immobilization of Pd on magnetite nanoparticles (MNPs) coated with dithizone. The activity of this catalyst was examined for the synthesis of various biaryls via the C–C coupling reaction of aryl halides and sodium tetraphenylborate or phenylboronic acid under mild reaction conditions. Fe3O4/SiO2–DTZ–Pd was characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, vibrating sample magnetometer, and scanning electron microscopy.

A supramolecular ensemble of a PBI derivative and Cu2O NPs: potential photocatalysts for the Suzuki and Suzuki type coupling reactions

The in situ generated supramolecular ensemble (2:Cu2O) of Cu2O NPs and aggregates of PBI derivative 2 exhibited excellent photocatalytic efficiency in the Suzuki–Miyaura and Suzuki type cross-coupling reactions under mild and eco-friendly conditions.

Synthesis, characterization, and application of palladium-dithizone immobilized on magnetic nanoparticles as an efficient and recoverable catalyst for Suzuki type coupling reactions

A novel, magnetically separable catalyst was synthesized by the immobilization of Pd on magnetite nanoparticles (MNPs) coated with dithizone. The activity of this catalyst was examined for the synthesis of various biaryls via the C–C coupling reaction of aryl halides and sodium tetraphenylborate or phenylboronic acid under mild reaction conditions. Fe3O4/SiO2–DTZ–Pd was characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, vibrating sample magnetometer, and scanning electron microscopy.

Gold/Palladium Alloy for Carbon-Halogen Bond Activation: An Unprecedented Halide Dependence.

New catalytic activity of gold/palladium alloy nanoclusters (NCs) for carbon-halogen bond activation is demonstrated. In the case of an aryl chloride, the inclusion of gold in a bimetallic catalyst is indispensable to achieve the coupling reactions. Gold has the unique effect of stabilizing palladium, such that Pd(2+) leached from clusters by means of spillover of chloride during oxidative addition. The thus-formed spillover intermediate further reacts heterogeneously in both Ullmann and Suzuki-type coupling reactions through a new type of mechanism. In the case of an aryl bromide, Ullmann coupling occurs through the spillover of bromide, similar to that of aryl chloride. However, a significant fraction of palladium also leached, which diminished the Ullmann coupling activity of the aryl bromide and, as a result, the order of reactivity was ArCl>ArBr. With regard to the activation of the C-Br bond towards a Suzuki-type reaction, the inclusion of a higher gold content in gold/palladium clusters stabilized palladium to prevent the leaching of Pd(2+) from the clusters by means of spillover of bromide. The spillover intermediate reacts heterogeneously with PhB(OH)2, palladium-rich gold/palladium, or pure palladium clusters; the oxidative addition of ArBr favors the extraction of palladium from the clusters, yielding Pd(2+) intermediates. The extracted intermediates react homogenously (Pd(2+/)Pd(0) catalysis) with PhB(OH)2, which results in the higher selectivity of the cross-coupling product. An initial step to observe such unprecedented halide dependency, together with the dynamic behavior of palladium on the surface of gold is the oxidative addition of Ar-X. A detailed insight into the first oxidative addition process was also examined by quantum chemical calculations.

Aggregates of the pentacenequinone derivative as reactors for the preparation of Ag@Cu2O core-shell NPs: an active photocatalyst for Suzuki and Suzuki type coupling reactions.

Aggregates of the pentacenequinone derivative 1 act as reactors and stabilizers for rapid and facile preparation of Ag@Cu2O core-shell nanoparticles (NPs) in aqueous medium. The in situ generated Ag@Cu2O core-shell hybrid materials enabled efficient visible light harvesting to catalyse the palladium free Suzuki-Miyaura and Suzuki type cross coupling reactions at room temperature.

Miniaturized catalysis: monolithic, highly porous, large surface area capillary flow reactors constructed in situ from polyhedral oligomeric silsesquioxanes (POSS).

A single-step molding process utilizing free-radical cross-linking reaction of vinyl POSS in microliter-sized dimensions leads to hierarchically-structured, mechanically robust, porous hybrid structures. Functional variants show excellent performance in Suzuki-type coupling reactions. Due to their small volume, long-term operational robustness, and potential chemical diversity, these materials are promising candidates for catalyst screening applications.

Routes to synthesis of porphyrins covalently bound to poly(carbazole)s and poly(fluorene)s: Structural and computational studies on oligomers

We report the synthesis, spectroscopic and computational characterization of carbazole and fluorene oligomers containing pendant porphyrins prepared through Suzuki type coupling reactions. Molecular modeling, combining ab initio and semiempirical PM6 methods, has been carried out to clarify the structural geometry of these oligomers, testing the viability of development of polymers with the above repeat units. Based on the above results, and attempts to polymerize these systems, indications are made of possible routes to synthesize poly(carbazole)s and poly(fluorene)s containing covalently bound porphyrins.

Ring‐Opening Metathesis Polymerization Based Pore‐Size‐Selective Functionalization of Glycidyl Methacrylate Based Monolithic Media: Access to Size‐Stable Nanoparticles for Ligand‐Free Metal Catalysis

Monolithic polymeric supports have been prepared by electron-beam-triggered free-radical polymerization using a mixture of glycidyl methacrylate and trimethylolpropane triacrylate in 2-propanol, 1-dodecanol, and toluene. Under appropriate conditions, phase separation occurred, which resulted in the formation of a porous monolithic matrix that was characterized by large (convective) pores in the 30 μm range as well as pores of <600 nm. The epoxy groups in pores of >7 nm were hydrolyzed by using poly(styrenesulfonic acid) (Mw = 69,400 g mol(-1), PDI=2.4). The remaining epoxy groups inside pores of <7 nm were subjected to aminolysis with norborn-5-en-2-ylmethylamine (2) and provided covalently bound norborn-2-ene (NBE) groups inside these pores. These NBE groups were then treated with the first-generation Grubbs initiator [RuCl2 (PCy3 )2 (CHPh)]. These immobilized Ru-alkylidenes were further used for the surface modification of the small pores by a grafting approach. A series of monomers, that is, 7-oxanorborn-5-ene-2,3-dicarboxylic anhydride (3), norborn-5-ene-2,3-dicarboxylic anhydride (4), N,N-di-2-pyridyl-7-oxanorborn-5-ene-2-carboxylic amide (5), N,N-di-2-pyridylnorborn-5-ene-2-carboxamide (6), N-[2-(dimethylamino)ethyl]bicyclo[2.2.1]hept-5-ene-2-carboxamide (7), and dimethyl bicyclo[2.2.1]hept-5-en-2-ylphosphonate (8), were used for this purpose. Finally, monoliths functionalized with poly-5 graft polymers were used to permanently immobilize Pd(2+) and Pt(4+), respectively, inside the pores. After reduction, metal nanoparticles 2 nm in diameter were formed. The palladium-nanoparticle-loaded monoliths were used in both Heck- and Suzuki-type coupling reactions achieving turnover numbers of up to 167,000 and 63,000, respectively.

Synthesis and Characterization of Polypyrrole−Palladium Nanocomposite-Coated Latex Particles and Their Use as a Catalyst for Suzuki Coupling Reaction in Aqueous Media

Polypyrrole-palladium (PPy-Pd) nanocomposite was deposited in situ from aqueous solution onto micrometer-sized polystyrene (PS) latex particles. The PS seed particles and resulting composite particles were extensively characterized with respect to particle size and size distribution, morphology, surface/bulk chemical compositions, and conductivity. PPy-Pd nanocomposite loading onto the PS seed latex particles was systematically controlled over a wide range (10-60 wt %) by changing the weight ratio of the PS latex and PPy-Pd nanocomposite. Pd loading was also controlled between 6 and 33 wt %. The conductivity of pressed pellets increased with the PPy-Pd nanocomposite loading and four-point probe measurements indicated conductivities ranging from 3.0 x 10(-1) to 7.9 x 10(-6) S cm(-1). Hollow capsule and broken egg-shell morphologies were observed by scanning/transmission electron microscopy after extraction of the PS component from the composite particles, which confirmed a PS core and PPy-Pd nanocomposite shell morphology. X-ray diffraction confirmed that the production of elemental Pd and X-ray photoelectron spectroscopy indicated the existence of elemental Pd on the surface of the composite particles. Transmission electron microscopy confirmed that nanometer-sized Pd particles were distributed in the shell. The nanocomposite particles functioned as an efficient catalyst for Suzuki-type coupling reactions in aqueous media for the formation of carbon-carbon bonds.

Synthesis and Stereochemistry of Highly Unsymmetric β,Meso-Linked Porphyrin Arrays

Porphyrin arrays with tailor-made photophysical properties and well-defined three-dimensional geometries constitute attractive synthetic targets in porphyrin chemistry. The paper describes a variable, straightforward synthetic procedure for the construction of beta,meso-linked porphyrin multichromophores in good to excellent yields. In a Suzuki-type coupling reaction beta-borylated 5,10,15,20-tetraarylporphyrins (TAPs) served as versatile building blocks for the preparation of a plethora of directly linked, unsymmetrically substituted di- and triporphyrins. Besides their interesting photophysical properties, especially the trimeric porphyrin arrays show exciting stereochemical features. The established protocols thus open a convenient entry into the synthesis of achiral and chiral, unsymmetrically substituted beta,meso-linked oligoporphyrins, e.g., for applications in biomedicine or nonlinear optics.

Potassium [1-(tert-Butoxycarbonyl)-1H-indol-2-yl]trifluoroborate as an Efficient Building Block in Palladium-Catalyzed Suzuki-Miyaura Cross Couplings

Potassium [1-(tert-butoxycarbonyl)-1H-indol-2-yl]tri-fluoroborate (1) was used in Suzuki-type coupling reactions. First, the best coupling conditions were assessed using bromobenzene as the electrophile. Then, 1 was successfully coupled with various aryl and hetaryl bromides. Finally, the reactivity of 1 towards coupling partners other than bromide derivatives was evaluated.

Synthesis of terpyridine-substituted calix[ n]arenes

Calix[ n]arenes ( n = 4,5) comprising 4-(2,2′:6′,2″-terpyridyl)-phenyl substituents at the upper rim were synthesized for the first time, employing Suzuki-type coupling reactions. All calix[ n]arene derivatives were prepared as cone conformers. The single crystal X-ray structure of cone-5,11,17,23-tetra{4-(2,2′:6′,2″-terpyridyl)-phenyl}-25,26,27,28-tetrabutoxycalix[4]arene 4 is analyzed in terms of structural rigidity and potential use of these ligands as novel synthons of cage-type metallosupramolecular assemblies.

Synthesis, photophysical, electrochemical, and electrochemiluminescent properties of 5,15-bis(9-anthracenyl)porphyrin derivatives

Novel 5,15-bis(9-anthracenyl)porphyrin derivatives (, ) were synthesized by stepwise Suzuki-type coupling reactions using anthracenyl-boronates bearing various electronically active moieties. Absorption spectra of these porphyrin conjugates reveal some degree of delocalisation with the directly linked chromophores, particularly in the case of anthracenyl-porphyrin bearing dimethylanilino moieties at the two extremities. Fluorescence and 77 K phosphorescence properties indicate that the excitation energy is invariably funnelled to the lowest singlet and triplet states of the porphyrin chromophore. The latter levels have been probed also by transient absorption spectroscopy, showing the typical triplet features detected in meso-substituted porphyrins. Extensive electrochemical studies have been performed to unravel the electronic properties of the newly synthesized porphyrins. Low-temperature cyclic voltammetry investigations showed that the anthracenyl-porphyrins are capable of undergoing as many as four electron transfer processes. In particular, by means of UV-Vis-NIR spectroelectrochemical measurements, a NIR-centred intramolecular photoinduced intervalence charge transfer (IV-CT) from a neutral N,N-dimethylanilino moiety to the N,N-dimethylanilino radical cation has been observed for the doubly-oxidised porphyrin (2+). The molecules also showed unexpected electrogenerated chemiluminescence properties, which revealed to be largely controlled by the electronic characteristics of the peripheral anthracenyl substituents. The structural and the electronic properties of these complexes have been also characterised by DFT calculations, as well as by X-ray crystallographic analyses.

Intramolecular charge transfer in photoexcited hydroxyterphenyls: Evidence for formation of terphenyl quinone methides in aqueous solution

The photochemistry of a number of p-terphenyls substituted with hydroxy and hydroxymethyl substituents at the terminal benzene rings has been studied in aqueous solution. Previous work has shown that a simple hydroxyl group can strongly activate appropriately substituted benzenes or biphenyls towards dehydroxylation, via its highly electron-donating nature upon deprotonation in S 1. The intermediates formed are the corresponding quinone methides (QMs) or biphenyl quinone methides (BQM). We show in this work that the methodology also works for appropriately substituted p-terphenyls. Thus, a number of p-terphenyls with the appropriate substituents at the terminal benzene rings were synthesized via consecutive Suzuki-type coupling reactions from commonly available starting materials. Although these terphenyls are much less soluble than their simpler biphenyl analogs, they were sufficiently soluble in aqueous CH 3CN or CH 3OH for their photosolvolytic reactivity to be studied by product studies and fluorescence measurements which are consistent with formation of terphenyl quinone methides (TQMs) as intermediates. Their quantum yields of formation are attenuated compared to the corresponding biphenyl and benzene analogs and one possible reason is the highly fluorescent nature of both phenol and phenolate forms.

New 2-(2-pyridyl)piperidines: synthesis, complexation of palladium and catalytic activity in Suzuki reaction

The syntheses of novel 2-(2-pyridyl)-6-alkyl piperidines are reported using intramolecular Mannich-based methodology. Preliminary evaluation of the catalytic activity of the corresponding (diamine)Pd(II) complexes in the preparation of biaryl derivatives through Suzuki-type coupling reaction showed high to quantitative conversions and catalyst loadings as low as 10 −3 mol %.

Poly(thienyl‐phenylene)s with macromolecular side chains by oxidative polymerization of well‐defined macromonomers

AbstractWell‐defined polystyrene (PSt), poly(ε‐caprolactone) (PCL) or poly(2‐methyloxazoline) (POx) based polymers containing mid‐ or end‐chain 2,5‐ or 3,5‐dibromobenzene moieties were prepared by controlled polymerization methods, such as atom transfer radical polymerization (ATRP), ring opening polymerization (ROP), or cationic ring opening polymerization (CROP). These polymers were subsequently modified by Suzuki type coupling reactions with 2‐thiophene boronic acid. The resulting polymers, containing a conjugated sequence with 2‐thienyl groups at the extremities, could be further used as macromonomers in chemical oxidative polymerization in the presence of anhydrous FeCl3. Poly(thienyl‐phenylene)s having the respective PSt or PCL chains as lateral subtituents were obtained in this way. All the starting, intermediate, or final polymers were structurally analyzed by spectroscopic methods (1H and 13C NMR, IR) and gel permeation chromatography (GPC) measurements. Thermal behavior of the macromonomers and final polymers was investigated by differential scanning calorimetry (DSC) analyses. Optical properties of the polymers were monitored by UV and fluorescence spectroscopy. The emission spectra of the polymers show a clear bathochromic shift of the λmax emission in all the cases with respect to the monomers because of the extending of the conjugation length. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 848–865, 2007.