Palladium-catalyzed Suzuki Reaction Research Articles

Tuning the Photophysical Properties of Flavins by Attaching an Aryl Moiety via Direct C-C Bond Coupling.

Palladium-catalyzed Suzuki reactions of brominated flavin derivatives (5-deazaflavins, alloxazines, and isoalloxazines) with boronic acids or boronic acid esters that occur readily under mild conditions were shown to be an effective tool for the synthesis of a broad range of 7/8-arylflavins. In general, the introduction of an aryl/heteroaryl group by means of a direct C-C bond has been shown to be a promising approach to tuning the photophysical properties of flavin derivatives. The aryl substituents caused a bathochromic shift in the absorption spectra of up to 52 nm and prolonged the fluorescence lifetime by up to 1 order of magnitude. Moreover, arylation of flavin derivatives decreased their ability to generate singlet oxygen.

Synthesis of tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazole-5-yl)-1H-pyrazole[3,4-d] pyrimidine-1-yl) ethoxy) propionate

Tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazole[3,4-d] pyrimidine-1-yl) ethoxy) propionate plays an important role in the whole synthesis route as an intermediate of target mTOR targeted PROTAC molecule PRO1. In this experiment, palladium catalyzed Suzuki reaction was used, the target compound tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazole[3,4-d]pyrimidine-1-yl)ethoxy)propionate (compound 3) was synthesized from 5-(4,4,5,5-tetramethyl-1,3,2-dioxobenzaldehyde-2-yl) benzo[d]oxazole-2-amine (compound 1) and 3-(2-{4-amino-3-iodine-1H-pyrazole[3,4-d]pyrimidine -1-ethoxy}propionic acid) tert-butyl ester (compound 2). The structure of the product was confirmed by 1H NMR, 13C NMR and HRMS. When the reaction time is 6 hours, the ratio of reactants n (compound 1): n (compound 2) = 1:2, the reaction solvent is DME: H2O (2:1, volume ratio), the reaction temperature is 90°C, the catalyst is Pd (PPh3)4, the base condition is Na2CO3, the best reaction condition can be obtained, and the yield is 96.7%.

Selective capture of Pd(II) from aqueous media by ion-imprinted dendritic mesoporous silica nanoparticles and re-utilization of the spent adsorbent for Suzuki reaction in water

The development of highly efficient adsorptive material for the selective capture of Pd(II), and re-utilization of spent Pd(II)-loaded adsorbent as an efficient catalyst for organic synthesis are of great significance, but challenging. Particularly, the heterogeneous palladium-catalyzed Suzuki reaction in aqueous media is much more challenging than that of homogeneous. Herein, several novel Pd(II) ion-imprinted polymers (PIIPs) based on dendritic fibrous silica particles are constructed by surface ion imprinting technology (SIIT), using Schiff base and pyridine groups functionalized organosilicon as functional monomer. The PIIP-3 prepared by 3 g of functional monomer exhibits the best adsorption performance, and shows ultrafast (10 min) and selective capture of Pd(II) with high uptake capacity (382.5 mg/g). Moreover, the waste Pd(II) loaded PIIP-3 (PIIP-3-Pd) can serve as a catalyst towards the Suzuki reaction in water, affording 94.2 % yield of the desired product. Interestingly, the PIIP-3-Pd can be reused 12 times without an appreciable decrease in catalytic activity, which is probably due to the imprinted cavity and specific recognition site of PIIP-3 can match and recapture Pd active species in a complex catalytic environment. Thus, this work demonstrates huge potentials of SIIT to enhance the selectivity of adsorption process and increase the lifetime of catalysts.

Facile Microwave Synthesis of Pd-Catalyzed Suzuki Reaction for Bis-6-Aryl Imidazo[1,2-a]Pyridine-2-Carboxamide Derivatives with PEG3 Linker

An efficient and facile synthetic procedure has been developed for the synthesis of novel series of Bis-6-aryl-imidazo[1,2-a]pyridine-2-carboxamide containing 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) derivatives (6a-6j). An application of the Palladium catalyzed Suzuki reaction on amine-(CH2)3-PEG3-(CH2)3-amine linked 6-bromo imidazo[1,2-a]pyridine-2-carboxamide was reported and their products are discussed. The reaction was optimized through numerous catalytic conditions for this strategy, and it was fixed with the best approach having advantages of less reaction time, higher degree of yield, most consumption of starting material, and selection of best catalyst for the success of the reaction. The ideal spectroscopic characterization (PMR, CMR, IR and MS) have been utilized for the finalization of the synthesized adducts.

Modular Synthesis of α-Substituted Alkenyl Acetals by a Palladium-Catalyzed Suzuki Reaction of α-Haloalkenyl Acetals with Organoboranes

AbstractA modular and straightforward synthetic strategy for the preparation of α-substituted alkenyl acetals has been developed. α-Haloalkenyl acetals react smoothly with (het)aryl boronic acids, aryl boronates, or B-alkyl-9-borabicyclo[3.3.1]nonanes through Pd-catalyzed Suzuki cross-coupling under mild conditions with good to high yields. This protocol features a broad substrate scope and good functional-group compatibility, and is easily scaled up.

A novel magnetic mesoporous Fe3O4@Void@mSiO2-Pd(0) nanochains with high heterogeneous catalysis efficiency for Suzuki coupling reaction

Abstract It is well known that palladium-catalyzed cross-coupling Suzuki reaction is very important way to build organic compound carbon skeleton. However, when some reactants such as chlorobenzene are used as substrates which has low reactivity, only moderately low yields were obtained using such kind of mobilized catalyst, Insufficient loading on the normal carrier, the problem of easy aggregation of palladium and large particle size of Pd were considered as reasons of it. A novel magnetic mesoporous Fe 3O4@Void@mSiO2 nanochains with yolk-shell structure have been first developed to solve the problems via magnetic-field induced distillation-precipitation polymerization together with a facile sol-gel method and the final calcination . Interestingly, we found that some pleated layers grown on the surface of Fe 3O4@void@mSiO2 nanochains during the hydrolysis of 3-aminopropyltriethoxysilane (KH-550) and special microstructures endow them with excellent porosity which are helpful for increasing the loading capacity of Pd nanoparticles. Owing to high aspect ratio and superparamagnetism , the magnetic nanochains can rotate in the water or organic solution and be separated and recycled easily with the drive of alternating magnetic field. In this catalysis system, the orderly mesoporous opening structure of the hollow mesoporous nanochains could effectively facilitate the transfer of reactant molecules, and the existence of the internal cavities would effectively prolong the action time of the Pd nanoparticles for the Suzuki reaction. The reaction yields of coupling reaction between bromobenzene/chlorobenzene and phenylboronic acid catalyzed by the nanochains can reach nearly 100% respectively. and the reaction yields can still maintain 92.93% and 60.86% after 7 cycles, respectively.

N,S-chelating triazole-thioether ligand for highly efficient palladium-catalyzed Suzuki reaction

1,2,3-Triazole-thioether compounds could serve as efficient ligands for Pd-catalyzed Suzuki reactions of various aryl iodides, bromides and chlorides. The reactions feature wide substrate scope and mild reaction conditions. Besides, shorter reaction time, lower catalyst loadings and quantitative yields with a turnover-frequency (TOF) value of up to 11,880 h−1 are other advantageous of this attractive protocol. The crystal structure analyses and computational studies revealed that the higher catalytic activity of the corresponding chelated palladium complex ascribed to the lower energy gap and the lower redox potential.

Copper-catalyzed Csp-chalcogen bond formation: Versatile approach to N-(3-(organochalcogenyl)prop-2-yn-1-yl)amides

This work describes the copper-catalyzed Csp-chalcogen bond formation through cross-coupling reactions of propynylbenzamides and diorganyl dichalcogenides at room temperature, under open atmosphere. Generally, the reactions have proceeded very smoothly, affording the new class of organochalcogen-containing propynylbenzamides in good yields. Notably, this protocol showed to be tolerant to neutral, electron-donating and electron-withdrawing substituents present in both reaction substrates. In addition, the applicability of the carbon-chalcogen bond as a reactive site has been proved by successfully employment of the N-methyl-N-(3-(butylselanyl)prop-2-yn-1-yl)benzamide as a precursor in palladium-catalyzed Suzuki and Sonogashira type reactions.

A simple and mild Suzuki reaction protocol using triethylamine as base and solvent

A simple and mild protocol for the palladium-catalyzed Suzuki reaction of aryl bromides and arylboronic acids is developed. The cross-coupling reactions can be performed at room temperature using 5.0 equiv. of Et3N as solvent and base without any ligands, and affording biaryl products in good yields. In addition, the chemoselecitive Suzuki reaction of bromo-N-methyliminodiacetic acid (MIDA) boronates with arylboronic acids can be achieved in this system, and various unsymmetrical terphenyls have been prepared in moderate yields by one-pot double Suzuki reactions.

Single atoms catalyze Suzuki reactions

As effective as the palladium-catalyzed Suzuki reaction is for forming carbon-carbon bonds, researchers see room for improvement. Homogeneous palladium catalysts can be tough to separate from produ...

Enantioselective Total Synthesis of Blennolide H and Phomopsis-H76 A and Determination of Their Structure.

This work reports on the enantioselective total synthesis of the two dimeric natural chromanone lactones phomopsis-H76 A (5) and blennolide H (6). Both syntheses could be achieved from chromane 11, which was obtained by an enantioselective Wacker-type cyclization with >99 % ee. The dimerization of the corresponding monomers was performed using a palladium-catalyzed Suzuki reaction. Moreover, within this work it was possible to revise the absolute configuration of phomopsis-H76 A and determine the relative as well as absolute configuration of blennolide H.

Convenient synthesis of 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines by sequential chemoselective Suzuki reaction followed by double C-N coupling

A convenient and regioselective synthesis of two series of indolo[2,3-b]quinolines, namely 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines, has been developed. The synthesis, proceeds in moderate to high yields, involving chemoselective palladium catalyzed Suzuki reaction of 2,3-dihaloquinolines with 2-bromophenylboronic acid, followed by a double Buchwald-Hartwig C-N coupling.

Synthesis and photophysical studies of novel 4-aryl substituted 2-phenyl-, 2-(fluoren-2-yl)- and 2-cymantrenylquinazolines

The synthesis of novel push–pull 2,4-disubstituted quinazolines was performed by the bromodeoxygenation of 2-phenyl-, 2-(fluoren-2-yl)- and 2-cymantrenylquinazolin-4-ones and subsequent palladium-catalyzed Suzuki reactions. According to the optical studies, derivatives containing 4-positioned 4-diethylaminophenyl substituent exhibit higher luminescence in toluene solutions as compared to acetonitrile ones.

Modification of Bischler-Möhlau indole derivatives through palladium catalyzed Suzuki reaction as effective cholinesterase inhibitors, their kinetic and molecular docking studies

Due to the immense importance of aryl indole nucleus, herein we report the palladium-catalyzed arylation of N-substituted 2-aryl indole utilizing Suzuki-Miyaura cross coupling methodology. The biological screening for cholinesterase inhibition of the resulted biaryl indole moieties was carried out to evaluate their pharmacological potential, expecting to involve the development of new therapeutics for various inflammatory, cardiovascular, gastrointestinal and neurological diseases. This research work also involved the use of utilization of microwave-assisted organic synthesis (MAOS) for the synthesis of Bischler-Möhlau indole which is further biarylated via palladium-catalyzed cross coupling reaction. All the synthetic compounds (3a-n) were tested for cholinesterase inhibition and exhibited high level of AChE inhibitory activities. Interestingly, compounds 3m and 3n were found to be dual inhibitors, however, remaining compound exhibited no inhibitory activity against BChE. The biological potential of the resulted compounds was explained on the basis of molecular docking studies, performed against AChE and BChE, exploring the probable binding modes of most potent inhibitors.

Extraction of Base from Eichhornia crassipes and Its Implication in Palladium‐Catalyzed Suzuki Cross‐Coupling Reaction

AbstractThe utilization of a sustainable and eco‐friendly alternative medium derived from water borne species Eichhornia crassipes (Common name: Water Hyacinth) for the Suzuki cross‐coupling reaction at room temperature was reported. The system provides an in situ basic condition via metal extraction from ash water extract of Eichhornia crassipes, which delivers a dual performance in the catalytic application. The distribution of metal contents in the ash was characterized by EDX (Energy‐dispersive X‐ray spectroscopy) analysis. The basicity of the medium may possibly be due to the formation of corresponding metal oxides or hydroxides in its water extract. The application of this ash water extract results in an effective cross‐coupling in palladium catalyzed Suzuki reaction without any external promoter or ligand. The central attraction of our reaction system is the fruitful utilization of highly abundant unwanted weeds instead of destruction of ecologically important plants or plant parts. The present system highlights an excellent green pathway that fits the global urge of sustainable development and will prevail wide application in variable synthetic studies.

Synthesis and luminescence properties of long-chain (2,7-carbazolyl)-adamantane copolymers

Several long-chain (2,7-carbazolyl) adamantane copolymers, with molecular weight ranging from 4500 to 6000, were synthesized by palladium-catalyzed Suzuki reaction using 1,5-bis (4-bromophenyl) adamantane and N-(2-ethylhexyl)-2,7-carbazole as building molecules. The copolymers were characterized by infrared, ultraviolet, nuclear magnetic resonance (NMR), fluorescence spectroscopies, and thermal analysis. It was found that the introduction of adamantyl group into the backbone of conjugated carbazole polymer significantly improves the thermal stability and spectral stability of the copolymer. These copolymers giving high color purity showed excellent comprehensive performance: the thermal decomposition temperature is up to 409 ~ 432 °C, glass-transition temperature is about 83 ~ 162 °C, fluorescence quantum efficiency is as high as 0.76 ~ 0.85. Hence, the synthesized copolymers have great potential for being used as new blue-light-emitting materials.

New trends in the cross-coupling and other catalytic reactions

Abstract A mini-review covers the latest achievements in the field of metal-mediated cross-coupling reactions among which are palladium-catalyzed Heck, Suzuki, cyanation and amination reactions. The aspects of the application of Pd nanoparticles (PdNPs) are discussed. The possibilities of the applications of Cu(I)-catalyzed reactions are described. Special emphasis is made on the synthesis of polymacrocyclic compounds like porphyrin dyads and triads, polyazacryptands bearing fluorophore groups using catalytic methods. The application of Pd-catalyzed CH-activation reactions for porphyrin modifications is described, the use of Lewis acids catalysis and organocatalysis for enantioselective C–C bond formation is considered with the emphasis on the application of immobilized organocatalyst.

Enantioselective Total Synthesis and Structure Confirmation of the Natural Dimeric Tetrahydroxanthenone Dicerandrol C.

The first enantioselective total synthesis of natural dicerandrol C (1 c) as its enantiomer containing a dimeric tetrahydroxanthenone skeleton is described starting from the enantiopure chromane 6 which was obtained through a Wacker-type cyclization with >99 % ee. For the formation of the dimeric skeleton a palladium-catalyzed Suzuki reaction was used. The synthesis allowed the confirmation of the absolute configuration of the dicerandrols.

ChemInform Abstract: Efficient Synthesis of 2‐Phenyl‐3‐substituted Furo/thieno[2,3‐b]quinoxalines via Sonogashira Coupling Reaction Followed by Iodocyclization and Subsequent Palladium‐Catalyzed Cross‐coupling Reactions.

In this paper, we report the successful synthesis of new 2-phenyl-3-substituted furo/thieno[2,3-b]quinoxaline derivatives from 2-chloro-3-methoxyquinoxaline and 2-chloro-3-(methylthio)quinoxaline by a three-step approach. The Sonogashira coupling reaction of the title compounds with terminal alkynes afforded 2-methoxy-3-(phenylethynyl)quinoxaline and 2-(methylthio)-3-(phenylethynyl)quinoxaline in good to excellent yields. The iodocyclization of the resulting compounds using ICl in CH2Cl2 afforded 3-iodo-2-phenylfuro[2,3-b]quinoxaline and 3-iodo-2-phenylthieno[2,3-b]quinoxaline. The subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting iodo compounds led to the formation of 2,3-disubstituded furo/thieno[2,3-b]quinoxaline in high yields. All compounds were fully characterized by FT-IR, mass, 1H NMR, and 13C NMR spectral data. The synthesized quinoxaline derivatives were also screened against the two bacterial strains Escherichia coli and Micrococcus luteus.

Palladium-Catalyzed Suzuki Reactions in Water with No Added Ligand: Effects of Reaction Scale, Temperature, pH of Aqueous Phase, and Substrate Structure

The heterogeneous palladium-catalyzed Suzuki reactions between model aryl bromides (4-bromoanisole, 4-bromoaniline, 4-amino-2-bromopyridine, and 2-bromopyridine) and phenylboronic acid have been successfully conducted in water with no added ligand at the 100 mL scale using 20–40 mmol of aryl bromide. The product yields associated with these substrates were optimized, and key reaction parameters affecting the yields were identified. The results clearly indicate that the reaction parameters necessary to achieve high yields are substrate-dependent. In addition, it is demonstrated that aqueous Suzuki reactions of substrates containing basic nitrogen centers can produce quantitative yields of desired products in the absence of added ligand.