Microwave-assisted Suzuki-Miyaura Research Articles

Porphyrazines with bulky peripheral pyrrolyl substituents – Synthesis via microwave-assisted Suzuki-Miyaura cross-coupling reaction, optical and electrochemical properties

Synthesis of novel aminoporphyrazines with peripheral 3,4-dihalide-2,5-dimethylpyrrol-1-yl and dimethylamino peripheral groups is reported. Cross-coupling Suzuki-Miyaura reaction with phenylboronic acid was used to convert magnesium(II) porphyrazine with dimethylamino and 3,4-dibromo-2,5-dimethylpyrrol-1-yl groups to an analogue with bulky 2,5-dimethyl-3,4-diphenylpyrrol-1-yl moieties. Microwave-assisted organic synthesis approaches were used in the Paal-Knorr reaction leading to the modified diaminomaleonitrile intermediates and the Suzuki-Miyaura reaction, which allowed the obtaining of porphyrazine derivative. All compounds were characterized using UV–Vis, 1H and 13C NMR, including 2D techniques, as well as MS (ES or MALDI). An X-ray analysis of magnesium(II) porphyrazine with peripheral 3,4-dibromo-2,5-dimethylpyrrol-1-yl and dimethylamino substituents was also performed. The electrochemical properties of all obtained porphyrazine macrocycles were assessed using cyclic and differential pulse voltammetry. The susceptibility of new macrocycles to oxidation/reduction processes depended on the presence of halide substituents in their macrocyclic periphery.

Efficient synthesis of new 6-arylphenanthridines based on microwave-assisted Suzuki–Miyaura cross-coupling and Pictet–Spengler dehydrogenative cyclization in a zinc chloride/[Bmim]BF4 mixture

An eco-friendly, efficient method for the synthesis of new bioactive 6-arylphenanthridines was developed based on consecutive MW-assisted Suzuki–Miyaura and Pictet–Spengler processes using a ZnCl2/[Bmim]BF4 mixture.

Efficient microwave-assisted Suzuki-Miyaura cross-coupling reaction of 3-bromo pyrazolo[1,5-a]pyrimidin-5(4H)-one: towards a new access to 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine derivatives.

A convenient and efficient synthetic route to C3-arylated 7-trifluoromethylpyrazolo[1,5-a]pyrimidin-5-one derivatives has been reported starting from 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-one through a Suzuki–Miyaura cross-coupling reaction. The arylation (heteroarylation) strategy can be performed using a wide variety of aryl and heteroaryl boronic acids and requiring a tandem catalyst XPhosPdG2/XPhos to avoid the debromination reaction. These optimized conditions were successfully extended to the synthesis of 7-, 8- and 9-arylated pyrimido[1,2-b]indazol-2-ones from their corresponding brominated starting materials. Furthermore, the second C-5 arylation of C3-arylated pyrazolo[1,5-a]pyrimidin-5-ones was achieved under standard Suzuki–Miyaura cross-coupling conditions, after activating the C–O bond of the lactam function with PyBroP, giving access to a small library of 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines in good to excellent yields. The interest of this approach has been highlighted by the synthesis of a known anti-inflammatory agent. Additionally, a preliminary biological evaluation has revealed that a number of derivatives display micromolar IC50 values against monoamine oxidase B, an important target in the field of neurodegenerative disorders.

Fabrication of Palladium Nanoparticles Supported on Natural Volcanic Tuff/Fe3O4 and Its Catalytic Role in Microwave-Assisted Suzuki–Miyaura Coupling Reactions

Natural minerals have a huge potential as stabilizers in the catalytic systems due to their high mechanical durability, porous surface, non-toxicity and abundance in nature. This study aims to the development of a magnetically retrievable, heterogeneous palladium catalytic system derived from volcanic tuff (VT), an abundant form of zeolite, for Suzuki–Miyaura coupling (SMC) reactions. For this purpose, a new catalyst support was designed by loading volcanic tuff with Fe3O4 (VT/Fe3O4) and palladium nanoparticles were prepared on VT/Fe3O4 via wet chemical reduction method (Pd NPs@VT/Fe3O4). Then, Pd NPs@VT/Fe3O4 was evaluated as a heterogeneous catalyst in the microwave-assisted production of biaryl via SMC reactions. Pd NPs@VT/Fe3O4 efficiently coupled various substituted aryl iodides, bromides and chlorides in a very short reaction time, solvent-free media and in an air environment. Catalytic tests indicated that Pd NPs@VT/Fe3O4 converted aryl halides into desired biaryls with a high yield up to 99%. Moreover, it was showed that Pd NPs@VT/Fe3O4 retained its stability and catalytic performance by producing 92% yield after eight successive cycles. This study demonstrated that VT can be a good alternative support alongside other known supports such as biopolymers, carbon and silica based materials and it can be utilized for the synthesis of different catalysts.

Synthesis and characterization of Pd(II) complexes bearing NS, CS, SNS and SCS ligands. Evaluation of their microwave assisted catalytic activity in C[sbnd]C coupling reactions

A series of coordination (Pd-NS,Pd-SNS, Pd-SNS-O) and organometallic (Pd-C and Pd-SCS) Pd(II) complexes supported by bidentate and tridentate ligands featuring sulphur moieties have been prepared. All ligands and their palladium complexes were fully characterized by various analytical techniques, including the unequivocal determination of the solid-state structures of the ligand L-SNS-O and the Pd-CS and Pd-NS complexes by single crystal X-ray diffraction analysis. Complexes Pd-NS,Pd-SNS,Pd-CS,Pd-SCS containing thioether groups were used as efficient catalysts in microwave-assisted Suzuki-Miyaura and Mizoroki-Heck C–C cross-coupling reactions, showing the organometallic catalysts (Pd-CS, Pd-SCS) to produce the better conversions, most likely due to enhanced thermal stability provided by the Pd–C bonds.

Solid-Phase Synthesis of Biaryl Cyclic Peptides Containing a Histidine-Phenylalanine Linkage

The feasibility of the solid-phase intramolecular 4(5)-arylation of a histidine residue to obtain biaryl cyclic peptides bearing a His-Phe linkage was established. The synthetic strategy involved the preparation of a linear peptidyl resin incorporating a 5-bromohistidine and a 4-boronophenylalanine, and its cyclization through the formation of the biaryl bond between the imidazole of histidine and the phenyl group of phenylalanine via a microwave-assisted Suzuki–Miyaura cross-coupling. This methodology was applied to the preparation of biaryl cyclic peptides consisting of a 3- or 5-residue ring, incorporating the His residue at the N- or the C-terminus and bearing a Leu-Leu spacer or a –NH2 group at the C-terminus. In the case of the 3-residue ring peptides, the position of the His did not influence the macrocyclization. In contrast, to obtain the 5-member ring biaryl cyclic peptides, the His residue should be located at the N-terminus. It was also observed that the Leu-Leu spacer is crucial for the intramolecular arylation. These results suggest that this approach could be useful for the preparation of a diversity of synthetic and natural biaryl cyclic peptides bearing a His-Phe linkage.

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety.

A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the macrolactamization of the resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diversity of synthetic or natural biaryl bicyclic peptides.

Solid-phase synthesis of biaryl cyclic peptides containing a histidine-tyrosine linkage

A solid-phase strategy for the synthesis of biaryl cyclic peptides containing a side-chain to side-chain His-Tyr linkage was developed. The key step was the macrocyclization of a linear peptidyl resin incorporating a 5-bromohistidine and a 3-boronotyrosine via the formation of the biaryl bond by means of a microwave-assisted Suzuki-Miyaura reaction. This method allowed direct access to biaryl cyclic peptides containing a 3- or 5-amino acid ring and bearing the histidine residue at the N- or the C-terminus, being especially conducive for analogues in which this amino acid is located at the C-terminus. This study also served to establish a strategy for the synthesis of biaryl cyclic peptides derived from the two hemispheres of the natural biaryl bicyclic peptides aciculitins.

A highly efficient precatalytic system (XPhos-PdG2) for the Suzuki-Miyaura cross-coupling of 7-chloro-1H-pyrrolo[2,3-c]pyridine employing low catalyst loading.

An expedient catalytic method for the synthesis of diverse 7-(hetero) aryl-1H-pyrrolo[2,3-c]pyridine analogues via microwave-assisted Suzuki-Miyaura cross-coupling reaction with excellent yield was developed. The method is found to be compatible with various boronic acids and potassium organotrifluoroborates. The formation of highly stable monoligated catalytic species is found to be instrumental in driving the reactions to excellent conversions in Suzuki-Miyaura coupling. Herein, we report our findings on the use of a highly efficient precatalytic system (XPhos-PdG2), containing a bulky monodentate biaryl ligand which allows the rapid reductive elimination to form the true monoligated Pd(0) catalytic species, thereby facilitating the Suzuki coupling reaction of 7-chloro, 6-azaindole system containing unprotected free N-H group with excellent conversions employing low catalyst loadings. Also, we observed that the use of near stoichiometric potassium organotrifluoroborate reagents as alternative coupling partners for boronic acids, which are prone to protodeboronation, resulted in excellent conversions.

Microwave-Assisted Suzuki-Miyaura Cross Coupling using Nickel as Catalyst to Rapidly Access to 3-Arylazetidine

Microwave-Assisted Suzuki-Miyaura Cross Coupling using Nickel as Catalyst to Rapidly Access to 3-Arylazetidine

Synthesis and characterization of functionalized polythiophene for polymer-sensitized solar cell

The synthesis of Poly[1,5-naphthyridine-(3-hexylthiophene)] (1) semi-conducting polymer has been accomplished by adopting both conventional and microwave-assisted Suzuki-Miyaura cross-coupling reaction between 3-hexylthiophene-2,5-diboronic ester and 2,6-dibromo-1,5-naphthyridine. The synthesized copolymer was characterized by modern spectroscopic techniques including percent reflectance (%R), gel permeation chromatography (GPC), cyclic voltammetry (CV), Raman spectroscopy, thermogravimetric analysis (TGA), FTIR and NMR. The morphology of copolymer was examined via FESEM. Optical bandgap was calculated from the absorption edge of %R and found 2.26 eV. The electrochemical and transport properties of 1 were investigated both in the bulk as well as in thin film form. Cyclic voltammetry (CV) results of 1 as a bulk form in H2SO4 solution indicated that the concentration of the polymer in the solution is not well defined because of polymer poor solubility in aqueous solutions. On the other hand, the sulfur group which works as electron donating makes the system more electron-rich. This can be explained by the absence of the reduction peak. For the thin film, two single oxidation peaks were obtained at around 0 V and 0.3 V for both cases. Different solvents can tune the transport properties of the polymer as can be seen from the two CVs where BF3 exhibited enhanced transport properties over ACN. This polymer was also employed in dye-sensitized solar cells as a photosensitizer. The solar cell under AM 1.5 G illumination at 100 mW/cm2 shows power conversion efficiency of 0.67% with an open-circuit voltage of 621 mV, a short circuit current of 2.0 mA/cm2, and a fill factor of 55%.

Development of 1-aryl-3-furanyl/thienyl-imidazopyridine templates for inhibitors against hypoxia inducible factor (HIF)-1 transcriptional activity

1,3-Disubstituted-imidazopyridines were designed for developing inhibitors against HIF-1 transcriptional activity. Designed compounds were rapidly synthesized from a key aromatic scaffold via microwave-assisted Suzuki-Miyaura coupling/CH direct arylation sequence. Evaluation of ability to inhibit the hypoxia induced transcriptional activity of HIF-1 revealed that the compound 2i and 3a retained the same level of the inhibitory activity comparing with that of known inhibitor, YC-1 (1). Identified, readily accessible 1-aryl-3-furanyl/thienyl-imidazopyridine templates should be useful for future drug development.

One-Pot Approach to N-Quinolyl 3'/4'-Biaryl Carboxamides by Microwave-Assisted Suzuki-Miyaura Coupling and N-Boc Deprotection.

N-Quinolyl biaryl carboxamides have received tremendous attention for their notable biological properties. Here we have described a general protocol for the preparation of N-quinolyl 3'/4'-biaryl carboxamides by microwave-assisted Suzuki-Miyaura cross-coupling reaction and N-Boc deprotection in one pot. This method, which did not require acids, was used to produce a series of N-quinolyl 3'/4'-biaryl carboxamides with excellent functional group tolerance and high yields (70% to 95%).

Synthesis of Functionalized Polythiophene as a Potenial Organic Semi-Conductor

The synthesis Poly[1,5-naphthyridine-(3-hexylthiophene)] (PN 3 HTh) semi-conducting polymer has been accomplished by adopting both conventional and microwave-assisted Suzuki-Miyaura cross-coupling reaction between 3-hexylthiophene-2,5-diboronic ester and 2,6-dibromo-1,5-naphthyridine. The electrochemical and transport properties of PN 3 HTh were investigated both in the bulk as well as in thin film form. These properties can be further tuned by changing the solvent and the nature of the electrode used. Consequently, cyclic voltammetry (CV) measurements were conducted using a potentiostat coupled with an electrochemical cell. The CV results of PN 3 HTh as a bulk form in H 2 SO 4 solution indicated that the concentration of the polymer in the solution is not well defined because of polymer poor solubility in aqueous solutions. On the other hand, the sulfur group which works as electron donating makes the system more electron-rich. This can explain by the absence of the reduction peak. For the thin film, two single oxidation peaks were obtained at around 0 V and 0.3 V for both cases. Different solvents can tune the transport properties of the polymer as can be seen from the two CVs where BF3 exhibited enhanced transport properties over ACN. The synthesized polymers were characterized by modern spectroscopic methods including IR and NMR.

Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.

Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.

High molecular weight mechanochromic spiropyran main chain copolymers via reproducible microwave-assisted Suzuki polycondensation

Mechanochromic spiropyran main chain copolymers with high and reproducible molar mass can be made using microwave-assisted Suzuki–Miyaura polycondensation.

A convenient synthesis of 4(5)-(hetero)aryl-1H-imidazoles via microwave-assisted Suzuki–Miyaura cross-coupling reaction

A simple and rapid access to a variety of 4(5)-arylated imidazoles via palladium-catalyzed Suzuki–Miyaura cross-coupling reaction is described. Coupling parameters were screened for efficient C-4 arylation of N-unprotected 4-iodoimidazole with a broad range of boronic acids under microwave irradiation. Twenty-one imidazole derivatives were synthesized in modest to excellent yields in short reaction times.

Application of bisphosphomide-palladium(II) pincer complex in Suzuki–Miyaura cross-coupling reaction under microwave irradiation

The bisphosphomide-based pincer complex [PdBr{2,6-{ Ph2PC(O)}2(C6H3)}] (2) has shown very high catalytic activity in Suzuki–Miyaura cross coupling reaction under microwave irradiation for a variety of aryl bromides and aryl boronic acids. The complex showed the same efficiency for gram scale reactions. Utility of a bisphosphomide-palladium pincer complex in microwave-assisted Suzuki–Miyaura cross-coupling reaction is described.

Oxadiazoline and ketoimine palladium(II) complexes supported on a chitosan membrane and their catalytic activity for the microwave-assisted Suzuki–Miyaura cross-coupling in water

The fused bicyclic Δ 4-1,2,4-oxadiazoline trans-( ▪) palladium(II) complex 1 (R = p-ClC 6H 4), in refluxing chloroform, undergoes N–O bond cleavage of the oxadiazoline ring to furnish the new ketoimine palladium(II) complex trans-( ▪) 2 bearing the 4-chloro-N-(5,5-dimethylpyrrolidin-2-ylidene)benzamide ligands. Complexes 1 (R = Me) and 2 (R = p-ClC 6H 4) were immobilized on a chitosan membrane and the systems acted as supported-catalysts (Pd-chit 1 and Pd-chit 2, respectively) for the model microwave-assisted Suzuki–Miyaura cross-coupling reactions in water using p-bromoanisole and phenylboronic acid to give p-methoxybiphenyl in excellent yield. The effects of catalyst loading, temperature, time, the phase-transfer agent tetrabutylammonium bromide (TBAB) and base were investigated, and the supported catalyst was recovered and reused up to seven times, with a gradual loss of catalytic activity.

Monodisperse noble metal nanoparticles stabilized in SBA-15: Synthesis, characterization and application in microwave-assisted Suzuki–Miyaura coupling reaction

A series of Pd and Pd/Au alloy nanoparticles (NPs) with narrow size distribution were encapsulated or stabilized by G4-poly (amido-amine) (G4-PAMAM, G represents the generation) planted in SBA-15. Monodisperse NPs are uniformly distributed in channels of SBA-15 as observed by TEM images. HRTEM, ICP and EDS results confirm the alloy structure of bimetallic NPs. A combination of N 2 adsorption–desorption analysis, ICP and GC was used to optimize the best amount of metal precursors to form catalysts. The as-prepared catalyst manifests outstanding activity and recyclability in microwave-assisted Suzuki–Miyaura coupling reaction when compared with commercial Pd/C. Meanwhile, Pd/Au alloy NPs exhibit higher activity than monometallic ones in catalyzing the coupling between aryl bromide/aryl chloride and arylboronic acid. The mechanism of the improvement of catalytic performance is discussed.