Palladium-catalyzed Suzuki Cross-coupling Reaction Research Articles

Design, synthesis and anti-Alzheimer's disease activity evaluation of C-3 arylated huperzine A derivatives

A series of C-3 arylated huperzine A (HPA) derivatives (1−30) were designed and synthesized in good yields via palladium-catalyzed Suzuki cross-coupling reaction. Cholinesterase inhibitory and neuroprotective activities of all 30 derivatives were evaluated. Cholinesterase inhibition results revealed that derivatives 2 and 15 exhibited dual inhibitory activity against both acetylcholinesterase (AChE inhibition: 2, IC50 = 1.205 ± 0.395 μM; 15, IC50 = 0.225 ± 0.062 μM) and butyrylcholinesterase (BChE inhibition: 2, IC50 = 8.598 ± 3.605 μM; 15, IC50 = 4.013 ± 0.068 μM), a feature not observed in huperzine A. Molecular docking results indicated that the introduction of aryl groups enhanced the affinity of the derivatives for the acyl-binding pocket of BChE, thereby limiting the hydrolysis of acetyl choline. However, these derivatives exhibited poor performance in cytotoxicity and neuroprotection assays.

β-Pyrrole functionalized push-pull BODIPYs: Synthesis, photophysical, electrochemical, thermal and computational studies

A series of [Formula: see text]-pyrrole functionalized push-pull BODIPYs BDP 1-06 were designed and synthesized via Palladium-catalyzed Suzuki cross-coupling reaction and by increasing the oxidation state of the sulfur atom in the thiazine ring. The effect of various donor entities on the photophysical, electrochemical, thermal, and computational studies of the BODIPY was investigated. The absorption spectra of the push-pull BODIPY BDP 2 show a red shift compared to the rest of the BDPs, due to strong donor-acceptor interaction. The phenothiazine-5,5-dioxide functionalized BODIPY BDP 6 exhibit a blue shift in the UV-vis region compared to the phenothiazine substituted BODIPY BDP 5 due to the weak donor ability of the phenothiazine-5,5-dioxide unit. The electrochemical studies were performed for the push-pull BODIPYs BDP 1–6 to analyze the effect of different donor groups on the redox properties of the BODIPY. The thermogravimetric analysis of the BODIPYs BDP 1–6 shows that BDP 2 exhibits excellent thermal stability compared to BDP 1, 3, 4, 5, and 6. The theoretical studies reveal that the phenothiazine-5,5-dioxide substituted BODIPY BDP 6 exhibits a large HOMO–LUMO gap compared to phenothiazine functionalized BODIPY BDP 5 due to the low donor ability of the phenothiazine-5,5-dioxide unit. The theoretical calculations were consistent with the experimental observations.

Integrating a Luminescent Porous Aromatic Framework into Indicator Papers for Facile, Rapid, and Selective Detection of Nitro Compounds.

Porous aromatic framework materials with high stability, sensitivity, and selectivity have great potential to provide new sensors for optoelectronic/fluorescent probe devices. In this work, a luminescent porous aromatic framework material (LNU-23) was synthesized via the palladium-catalyzed Suzuki cross-coupling reaction of tetrabromopyrene and 1,2-bisphenyldiborate pinacol ester. The resulting PAF solid exhibited strong fluorescence emission with a quantum yield of 18.31%, showing excellent light and heat stability. Because the lowest unoccupied molecular orbital (LUMO) of LNU-23 was higher than that of the nitro compounds, there was an energy transfer from the excited LNU-23 to the analyte, leading to the selective fluorescence quenching with a limit of detection (LOD) ≈ 1.47 × 10−5 M. After integrating the luminescent PAF powder on the paper by a simple dipping method, the indicator papers revealed a fast fluorescence response to gaseous nitrobenzene within 10 s, which shows great potential in outdoor fluorescence detection of nitro compounds.

Porphycenes as broad-spectrum antimicrobial photosensitizers. Potentiation with potassium iodide

Two novel meso-tetrasubstituted porphycenes (Pc-Cbz and Pc-NEt2) have been synthesized by palladium-catalyzed Suzuki cross-coupling reactions over 9,10,19,20-tetrakis(4-iodophenyl)porphycene. Pc-Cbz contains four carbazole groups on the periphery of the tetrapyrrolic macrocycle. Instead, Pc-NEt2 presents four basic tertiary amine substituents, which can be protonated at physiological pH, acquiring four positive charges. Both photosensitizers (PSs) were designed to evaluate the effect of different substitution patterns on the photodynamic inactivation of microorganisms. Their absorption and fluorescence properties were almost unmodified regardless of the substituent groups on the periphery. The characteristic red emission makes them promising fluorescent probes for cell imaging. Moreover, both macrocycles were able to generate reactive oxygen species by both photodynamic mechanisms under aerobic light irradiation. The photokilling action of these PSs was assessed in vitro against Candida albicans (yeast), Staphylococcus aureus (Gram-positive bacterium), and Escherichia coli (Gram-negative bacterium). Our results demonstrate that the peripheral substitution significantly affected the photoinactivation performance. Thus, Pc-NEt2 was more effective than Pc-Cbz in killing microorganisms using lower concentrations and shorter irradiation periods, evidencing that external substitution is a main structural feature. Also, the photoinactivation efficiency mediated by these porphycenes was potentiated by adding KI. Under these conditions, a complete eradication of all pathogenic microorganisms was obtained by combining Pc-NEt2 and KI. Therefore, Pc-NEt2 can be used as an effective broad-spectrum antimicrobial PS. Accordingly, this work stands out as a promising starting point for the design of new porphycene-based PSs for photodynamic inactivation (PDI) of microorganisms. Our outcomes also disclose that the combination of these PSs with KI is an important factor in order to improve the PDI treatments and the current antimicrobial therapies.

Efficient Synthesis of Novel 1,3,4-Oxadiazoles Bearing a 4-N,N-Dimethylaminoquinazoline Scaffold via Palladium-Catalyzed Suzuki Cross-Coupling Reactions.

Two series of novel (symmetrical and unsymmetrical) quinazolinylphenyl-1,3,4-oxadiazole derivatives were synthesized using palladium-catalyzed Suzuki cross-coupling reactions. The presented synthetic methodology is based on the use of bromine-substituted 2-phenyl-4-N,N-dimethylaminoquinazolines and either a boronic acid pinacol ester or a diboronic acid bis(pinacol) ester of 2,5-diphenyl-1,3,4-oxadiazole. The reactions are conducted in a two-phase solvent system in the presence of catalytic amounts of [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), sodium carbonate, and tetrabutylammonium bromide, which plays the role of a phase-transfer catalyst. The luminescence properties of the obtained compounds are discussed in the context of applying these compounds in optoelectronics. Specifically, two highly-conjugated final products: N,N-dimethyl-2-phenyl-6-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4-amine (8f) and 6,6′-(4,4′-(1,3,4-oxadiazole-2,5-diyl)bis(4,1-phenylene))bis(N,N-dimethylquinazolin-4-amine (9f), which contain a 1,3,4-oxadiazole moiety connected to a quinazoline ring by a 1,4-phenylene linker at the 6 position, exhibit strong fluorescence emission and high quantum yields.

Copper-Catalyzed Aminoboration from Hydrazones To Generate Borylated Pyrazoles.

Herein we report an aminoboration reaction that employs inexpensive, Earth-abundant, and commercially available Cu(OTf)2 as an effective catalyst in the direct addition of B-N σ bonds to C-C π bonds, generating borylated pyrazoles, which are useful building blocks for drug discovery. By nature of the mechanism, the reaction produces exclusively one regioisomer and tolerates groups incompatible with alternative lithiation/borylation and iridium-catalyzed C-H activation/borylation methods. The reaction can be scaled up, and the resulting isolable pyrazole pinacol boronates can be further functionalized through palladium-catalyzed Suzuki cross-coupling reactions.

Synthesis of 3,4-Biaryl-2,5-Dichlorothiophene through Suzuki Cross-Coupling and Theoretical Exploration of Their Potential Applications as Nonlinear Optical Materials

We report herein the efficient one-pot synthesis of 3,4-biaryl-2,5-dichlorothiophene derivatives (2a–2i) via a palladium-catalyzed Suzuki cross-coupling reaction. A series of thiophene derivatives were synthesized, starting from 3,4-dibromo-2,5-dichlorothiophene (1) and various arylboronic acids using Pd(PPh3)4 and K3PO4 with moderate to good yields. For further insights about the structure and property relationship, density functional theory (DFT) calculations were performed. A relaxed potential energy surface (PES) scan was performed to locate the minimum energy structure. A frontier molecular orbitals analysis was performed to explain the reactivity of all synthesized derivatives. As the synthesized derivatives had extended conjugations, therefore the first hyperpolarizability (βo) was calculated to investigate their potential as non-linear optical (NLO) materials and significant βo values were found for the 2b and 2g derivatives.

Synthesis of New 2-Arylbenzo[b]furan Derivatives via Palladium-Catalyzed Suzuki Cross-Coupling Reactions in Aqueous Media

A series of novel benzofuran derivatives containing biaryl moiety were designed and synthesized by the Suzuki cross-coupling reactions. The reactions, performed in the presence of K2CO3, EtOH/H2O and Pd(II) complex as catalyst, gave the corresponding products in good to excellent yields. The methodology allows the facile production of heterobiaryl compounds, a unique architectural motif that is ubiquitous in medicinal chemistry.

Total Synthesis of (±)-Exotine B.

The heterodimeric indole/coumarin natural product exotine B was synthesized for the first time. The carbon skeleton of the natural product was formed rapidly by a palladium-catalyzed Suzuki cross-coupling reaction and a gallium-catalyzed three-component [4 + 3] cycloaddition reaction. An alternative biosynthesis of exotine B is proposed based on the total synthesis. Improved syntheses of coumarin natural products gleinadiene and coumurrayin are also reported.

Strategy Toward Tuning Emission of Star-Shaped Tetraphenylethene-Substituted Truxenes for Sky-Blue and Greenish-White Organic Light-Emitting Diodes

Star-shaped, C3-symmetric, tetraphenylethene (TPE) and 2,3,3-triphenylacrylonitrile (TPAN)-substituted truxenes 7, 8, and 9 were designed and synthesized by the palladium-catalyzed Suzuki and Sonogashira cross-coupling reactions. The TPE-substituted truxenes 7 and 8 show aggregation-induced emission behavior, whereas TPAN-substituted truxene 9 shows aggregation-caused quenching effect in tetrahydrofuran/water medium due to the π–π stacking. The computational calculation on truxenes 7–9 was performed, which reveals that in truxene 9, the electron density transfers from truxene to TPAN. The truxenes 7–9 showed high thermal stability as the 10% weight loss temperature is more than 400 °C. The ionization potentials close to 6.0 eV were estimated for the solid samples of truxenes 7–9 by photoelectron emission spectrometry. Solid samples of the studied truxenes exhibited strong emission with high quantum yields (up to 47%). Electroluminescent properties of truxene derivatives 7–9 were investigated in solution-p...

Organic phototransistors with bulk heterojunction sensing-channel layers containing soluble difluorinated diketopyrrolopyrrole acceptor

Here we report synthesis of a difluorinated diketopyrrolopyrrole (DPP) derivative, 3,6-bis(5-((E)-3,5-difluorostyryl)thiophen-2-yl)-2,5-bis(2-ethylhexyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (EHD3FV), and its application as a photosensing electron acceptor in the bulk heterojunction (BHJ)-type organic phototransistors (OPTRs). EHD3FV was synthesized via the palladium-catalyzed Suzuki cross-coupling reaction between 3,6-bis(5-bromothiophen-2-yl)-2,5-bis(2-ethylhexyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione and trans-2(3,5-difluorophenyl) vinyl boronic acid pinacol ester. The pristine EHD3FV film showed optical absorption up to >850 nm, while its highest occupied molecular orbital (HOMO) energy reached −5.87 eV. The EHD3FV molecules were mixed with poly(3-hexylthiophene) (P3HT) leading the BHJ (P3HT:EHD3FV) sensing-channel layers for OPTRs. The OPTRs fabricated exhibited noticeable photoresponses upon illumination with different wavelengths of visible light (550 nm and 700 nm). The best responsivity (photoresponse) was achieved at the 8:2 (P3HT:EHD3FV) composition, even though the transistor performances in the dark became lower as the EHD3FV content increased. The present result supports the capability of EHD3FV as a photosensing electron acceptor in the BHJ-type OPTRs.

ChemInform Abstract: Simultaneous Exploration of TBAF·3H2O as a Base as well as a Solvating Agent for the Palladium Catalyzed Suzuki Cross‐Coupling of 4‐Methyl‐7‐nonafluorobutylsulfonyloxy Coumarins under Microwave Irradiation.

Abstract A concise, efficient and facile protocol for the synthesis of a variety of 4-methyl-7-aryl/heteroaryl coumarins has been developed by utilizing the palladium catalyzed Suzuki cross-coupling reaction of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin with a wide range of electronically diverse boronic acids under microwave irradiation. In the presence of a suitable catalyst, ligand and base, the coupling reaction proceeded smoothly to give the biaryls in satisfactory to exceptional yields. The dual role of TBAF·3H 2 O as a base as well as a solvating agent and the utilization of dppp as a ligand with moderate bite angle (91°) were found to be instrumental for the success of the reaction. Prominent features of this optimization conditions include: shorter reaction times, good to excellent yield and exceptional tolerance to a wide variety of functional groups.

Simultaneous exploration of TBAF·3H 2 O as a base as well as a solvating agent for the palladium catalyzed Suzuki cross-coupling of 4-methyl-7-nonafluorobutylsulfonyloxy coumarins under microwave irradiation

A concise, efficient and facile protocol for the synthesis of a variety of 4-methyl-7-aryl/heteroaryl coumarins has been developed by utilizing the palladium catalyzed Suzuki cross-coupling reaction of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin with a wide range of electronically diverse boronic acids under microwave irradiation. In the presence of a suitable catalyst, ligand and base, the coupling reaction proceeded smoothly to give the biaryls in satisfactory to exceptional yields. The dual role of TBAF·3H2O as a base as well as a solvating agent and the utilization of dppp as a ligand with moderate bite angle (91°) were found to be instrumental for the success of the reaction. Prominent features of this optimization conditions include: shorter reaction times, good to excellent yield and exceptional tolerance to a wide variety of functional groups.

ChemInform Abstract: A Simple and Novel Amide Ligand Based on Quinoline Derivative Used for Palladium‐Catalyzed Suzuki Coupling Reaction.

Abstract This paper discusses the synthesis of the amide ligand N,N-diisopropyl quinoline-2-carboxamide from quinoline-2-carboxylic acid and diisopropylamine. The prepared ligand was utilized in the palladium catalyzed Suzuki cross-coupling reaction in ethanol-water 1:1 (v/v). The reaction exhibited high catalytic efficiency with low Pd loading (0.05 mol %) under mild reaction conditions (at 60–90 °C under air atmosphere). In this study, the catalyst was successfully used in coupling reactions between various aryl halides with phenylboronic acid to obtain desired products in excellent yields. Spectrometric methods of 1 H NMR, 13 C NMR, and HR-MS were used to characterize this amide ligand, and its binding properties toward the Pd center were also investigated in detail via HR-MS measurements.

A facile access for the synthesis of some C-2 substituted imidazopyrazines by utilizing the palladium catalyzed Suzuki cross-coupling reaction under microwave irradiation

Abstract A rapid, efficient, and facile synthesis of an assortment of C-2 substituted imidazopyrazines has been achieved by utilizing the palladium catalyzed Suzuki cross-coupling of 2-bromo-1H-imidazo[4,5-b]pyrazine with various boronic acids under microwave irradiation. The utilization of (A-taphos)2PdCl2 as a catalyst in combination with CsF as base and DME-H2O (4:1) as the solvent system at 100 °C procured the diaryls in acceptable to excellent yields. Prominent features of this developed methodology include short reaction times, fewer side products, and exceptional tolerance to a wide variety of functional groups.

A simple and novel amide ligand based on quinoline derivative used for palladium-catalyzed Suzuki coupling reaction

This paper discusses the synthesis of the amide ligand N,N-diisopropyl quinoline-2-carboxamide from quinoline-2-carboxylic acid and diisopropylamine. The prepared ligand was utilized in the palladium catalyzed Suzuki cross-coupling reaction in ethanol-water 1:1 (v/v). The reaction exhibited high catalytic efficiency with low Pd loading (0.05 mol %) under mild reaction conditions (at 60–90 °C under air atmosphere). In this study, the catalyst was successfully used in coupling reactions between various aryl halides with phenylboronic acid to obtain desired products in excellent yields. Spectrometric methods of 1H NMR, 13C NMR, and HR-MS were used to characterize this amide ligand, and its binding properties toward the Pd center were also investigated in detail via HR-MS measurements.

Synthesis, spectral characteristics and electrochemistry of symmetrically substituted hybrids derived from 2,5-bis(4-bromophenyl)-1,3,4-oxadiazole under Suzuki cross-coupling reaction

New symmetrically substituted derivatives of 2,5-bis(4-arylphenyl)-1,3,4-oxadiazole were prepared from 2,5-bis(4-bromophenyl)-1,3,4-oxadiazole and various thiophene-, furan-, pyridine- or benzene-containing boronic acids by a palladium catalyzed Suzuki cross-coupling reaction under the conditions of the phase transfer catalysis. The structure of the products, the absorption and emission spectra and their electrochemistry were also studied.

Selective C-arylation of 2,5-dibromo-3-hexylthiophene via Suzuki cross coupling reaction and their pharmacological aspects.

The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc.) present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl)-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenyl)thiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds.

ChemInform Abstract: Palladium‐Catalyzed Suzuki Cross‐Couplings of N′‐Mesyl Arylhydrazines via C—N Bond Cleavage.

An efficient palladium-catalyzed Suzuki cross-coupling reaction of N′-mesyl arylhydrazine with aryl boronic acid is described, which affords the corresponding biaryl compounds in high yields. This transformation proceeds through C–N bond cleavage under mild conditions.

An efficient synthesis of 4-substituted coumarin derivatives via a palladium-catalyzed Suzuki cross-coupling reaction

An efficient Pd-catalyzed Suzuki cross-coupling reaction of sterically crowded 4-chlorocoumarin derivatives with air- and moisture-stable potassium organotrifluoroborates is developed. This methodology has been used to generate a series of novel alkyl, aryl, and vinyl substituted coumarin derivatives in good to excellent yields. The twisted conformation of the vinyl groups in the X-ray crystal structures of (2-oxo-4-vinyl-2H-chromen-3-yl)methyl acetate (2) and (2-oxo-4-vinyl-2H-chromen-3-yl)methyl 2,2,2-trichloroacetimidate (3), along with the atropisomerism of 3-(hydroxymethyl)-4-(2-methoxyphenyl)-2H-chromen-2-one (1d), are evidence of the steric crowding in these adducts.