Catalyzed Suzuki Cross-coupling Reaction Research Articles

Enhanced support effects in single-atom copper-incorporated carbon nitride for photocatalytic suzuki cross-coupling reactions

Conditioning the nature of metal active sites for better performance by well designing and constructing the support material is always appealing in heterogeneous catalysis. Herein, Cu species was introduced into the bulk phase of carbon nitride to strengthen the interlayer connection and optimize the electronic structure. The resulting material (CN-Cu) demonstrated an enhanced support effect for Pd catalyzed Suzuki cross-coupling reactions under light illumination. Detailed characterizations showed that Cu species were atomically incorporated in intra/interlayer of CN framework through coordinating with pyridinic nitrogen, leading to improved light absorption and more efficient charge carrier transfer. More importantly, the electronic effect of CN-Cu to the surface Pd was enhanced by the electron drift from Cu to N, thereby rendered an electron-rich Pd surface. Such Pd surfaces allowed faster electron injection from Pd(0) to the LUMO of aryl halides and therefore accelerate the rate-determining step of the coupling reaction.

A detailed theoretical investigation to unravel the molecular mechanism of the ligand-free copper-catalyzed Suzuki cross-coupling reaction.

The Suzuki-Miyaura coupling (SMC) represents a very efficacious method for constructing C-C bonds in organic synthesis. The ligand-free variants of SMC have been grabbing attention these days. Despite this momentousness, the mechanistic details of the ligand-free variants are scant in the literature. Herein, we have carried out a detailed mechanistic investigation into the ligand-free Cu-catalyzed SMC of unsaturated organic halides with aryl boronic acid with the aid of density functional theory (DFT) calculations employing the conductor-like polarizable continuum model (CPCM) method. The present study elucidates that in the absence of ancillary ligands on the metal, the substrates, base, and solvent molecules could act as pseudo-ancillary ligands to facilitate the cross-coupling reaction. The investigation further revealed that unsaturated halides like alkynyl halides/vinyl halides could act as good ancillary ligands for copper by forming a Cu-π intermediate and promoting a facile transmetalation process. However, regarding the oxidative addition and reductive elimination steps, a concerted pathway is observed contrary to Pd catalyzed Suzuki coupling, owing to the instability of Cu(III) species and the favourability of Csp2-Csp bond formation. In the whole set of mechanisms explored, oxidative addition/oxidative nucleophilic substitution was the rate-determining step in all the cases. A thermodynamically stable π-coordinated intermediate species where the substrate and base molecule are coordinated to the metal center is identified as the rate-determining species for the ligand-free Suzuki cross-coupling reaction. The presence of the aforesaid intermediate increases the energy span and consequently the activation barrier for the rate-determining step. This study unveiled a theoretical rationale for the high-temperature requirement in the ligand-free Cu-catalyzed SMC reaction.

Design, synthesis and characterization of π-conjugated 2,5-diphenylsubstituted-1,3,4-oxadiazole-based D-π-A-π’-D′ form of efficient deep blue functional materials: Photophysical properties and fluorescence “Turn-off” chemsensors approach

This paper primarily deals with the design and synthesis of three novel conjugated organic molecules containing 1,3,4-oxadiazole unit (abbreviated as CHEM-6(a-c)) with Donor-π-Acceptor-π’-Donor’ structures by utilizing palladium catalyzed Suzuki cross coupling reaction. Molecular structures of these compounds were characterized by using various spectroscopic and analytical techniques namely 1H NMR, 13C NMR, FT-IR, GC–MS and elemental analysis. Optical properties of these compounds have been investigated by using UV–visible absorption and fluorescence spectroscopy. Also, the PL investigations on solid state samples (as thin films) were carried out. Furthermore, solvatochromism and Density Functional Theory (DFT) computations are studied in detail. The experimentally measured optical band gap (Egopt) values of compounds CHEM-6a, CHEM-6b and CHEM-6c were determined to be 3.11, 3.03 and 2.70 eV, respectively. The DSC and TGA results revealed that the compounds exhibit good thermal stabilities. Current results indicate that the compounds CHEM-6(a-c) are promising candidates and could play an important role in the field of optoelectronic devices and possibly find potential applications in development of OLEDs. In addition, the compounds CHEM-6(a-c) showed an interesting property of chemical sensing for Hg(II) ion which can be clearly observed by naked eyes from the changes in solution color and fluorescence (under UV excitation).

Highly efficient one pot palladium-catalyzed synthesis of 3,5-bis (arylated) pyridines: Comparative experimental and DFT studies

Many different alkyl and aryl substituted pyridine based organic derivatives have been synthesized due to its uniqueness pyridine core. However, the transition metal catalyzed Suzuki cross coupling reaction has provided an easy route to the synthesis of alkyl and aryl substituted pyridine based organic compounds. Herein, we reported the arylated pyridines derivatives: 3, 5-bis (4-(trifluoromethoxy) phenyl) pyridine (BTFMP), 3,5-bis(4-bromophenyl)pyridine(BBPP), 3,5-bis(4-phenoxyphenyl)pyridine (BPPP) and 3,5-bis(2,5-dimethoxyphenyl)pyridine (BDMPP) by cross coupling Suzuki methodology for the first time. All derivatives have been characterized through 1H NMR, 13CNMR, 19F NMR and FT-IR spectroscopic techniques. Two compounds (BPPP) and (BDMPP) exist in the form of crystals among studied compounds. Therefore, SC-XRD has been performed for BPPP and BDMPP. In addition, computational studies using density functional theory (DFT) have been carried out in order to compare the DFT based data with the experimental findings. The optimization, FT-IR, natural bond orbitals (NBOs), frontier molecular orbitals (FMOs) and nonlinear optical (NLO) calculations of all derivatives have been performed using B3LYP/6-311G(d,p) level. The simulated HOMO-LUMO energy difference is observed to be large which shows the kinetic stability of the molecules. The molecular stability also originating from charge delocalization and hyper conjugative interactions has been elucidated by NBOanalysis. MEP surfaces are also developed of entitled molecules. The NLO data pointed out that the first order hyperpolarizability for BTFMP, BBPP and BPPP is greater among studied molecules than the standard molecule.

Mitochondrial Impairment by Cyanine-Based Small Molecules Induces Apoptosis in Cancer Cells.

Mitochondrion, the powerhouse of the cells, has emerged as one of the unorthodox targets in anticancer therapy due to its involvement in several cellular functions. However, the development of small molecules for selective mitochondrial damage in cancer cells remained limited and less explored. To address this, in our work, we have synthesized a natural product inspired cyanine-based 3-methoxy pyrrole small molecule library by a concise strategy. This strategy involves Vilsmeier and Pd(0) catalyzed Suzuki cross-coupling reactions as key steps. The screening of the library members in HeLa cervical cancer cells revealed two new molecules that localized into subcellular mitochondria and damaged them. These small molecules perturbed antiapoptotic (Bcl-2/Bcl-xl) and pro-apoptotic (Bax) proteins to produce reactive oxygen species (ROS). Molecular docking studies showed that both molecules bind more tightly with the BH3 domain of Bcl-2 proteins compared to obatoclax (a pan-Bcl-2 inhibitor). These novel small molecules arrested the cell cycle in the G0/G1 phase, cleaved caspase-3/9, and finally prompted late apoptosis. This small molecule-mediated mitochondrial damage induced remarkably high cervical cancer cell death. These unique small molecules can be further explored as chemical biology tools and next-generation organelle-targeted anticancer therapy.

Photophysical, thermal properties, solvatochromism and DFT/TDDFT studies on novel conjugated D-A-π-A-D form of small molecules comprising thiophene substituted 1,3,4-oxadiazole

In this paper, we report the design and synthesis of a series of novel conjugated thiophene substituted 1,3,4-oxadiazole derivatives BSTO-4(a-f) of Donor-Acceptor-π-Acceptor-Donor form by utilizing palladium catalyzed Suzuki cross coupling reaction. Structures were characterized by using spectroscopic techniques namely FT-IR, 1H NMR, 13C NMR and Mass spectra. Their thermal, photophysical and solvatochromic properties were studied in detail. Also, the PL investigations in the solid state were carried out. Furthermore, theoretical calculations such as density functional theory (DFT) were performed to get a better understanding of the intramolecular charge transfer property and electronic structures of the compounds. Experimentally measured optical bandgap values are in the range 3.02 to 3.54 eV. All compounds exhibit Stokes shifts in the range of 2776–3964 cm−1 and fluorescence quantum yields (Φf) in the range of 0.06–0.70 in chloroform. These derivatives exhibit high thermal stability that is the 5% weight loss temperature of derivatives are in the range 178–356 °C and the compounds BSTO-4(b, e and f) had the glass transition temperatures (Tg) at 107 °C, 147 °C and 68 °C, respectively. These results demonstrate that the novel thiophene substituted 1,3,4-oxadiazole compounds are promising candidates for potential applications in development of OLEDs, organic electronic devices/optoelectronic devices.

Highly active and recyclable heterogeneous palladium catalyst derived from guar gum for fabrication of biaryl compounds.

In this study, a novel highly efficient heterogeneous palladium catalyst (GG-Pd) was prepared using guar gum, which is an environmentally friendly, easily available, fairly cheap, and renewable natural bio-polymer. Detailed characterization of GG-Pd catalyst was successfully performed by FT-IR, TG/DTG, SEM, EDS, XRD, and ninhydrin test, and it was evaluated as a heterogeneous catalyst against Suzuki-Miyaura coupling reactions of a series of aryl halides with phenylboronic acid. Catalytic performance studies showed that GG-Pd efficiently catalyzed Suzuki cross coupling reactions under solvent-free media and for a very short reaction time (5 min). Moreover, reusability tests showed that GG-Pd catalyst could be reused at least ten times with a minor decrease of its catalytic performance. Additionally, it was found that palladium leaching from the designed support was very minimal. This study shows that GG-Pd catalyst is a very useful and highly stable heterogeneous catalyst for Suzuki-Miyaura coupling reactions in terms of high catalytic performance and recyclability.

Highly conjugated D-π-A-π-D form of novel benzo[b]thiophene substituted 1,3,4‑oxadiazole derivatives; Thermal, optical properties, solvatochromism and DFT studies

We have designed and synthesized a series of novel highly conjugated Donor-π-Acceptor-π-Donor form of unsymmetrical benzo[b]thiophene substituted 1,3,4‑oxadiazole derivatives UBTO-3(a–e) by utilizing Wittig Reaction followed by palladium catalyzed Suzuki cross coupling reaction and characterized by using standard spectroscopic techniques viz., 1H, and 13C NMR, FT-IR and GC–MS. To improve the intramolecular charge transfer property and to explore the optical properties of target compounds, Donor-Acceptor-Donor groups are linked via extending π conjugation through a phenyl spacer with para linkages. Optical/solvatochromic properties are studied in detail by UV–Vis absorption and fluorescence spectroscopy. Optical bandgap values were ranging from 2.266 to 2.704 eV. The derivatives exhibit high thermal stability that is the 5% weight loss temperature of derivatives are in the range 204–367 °C and the glass transition temperatures of the compounds UBTO-3(c, d and e) are at 146 °C, 140 °C and 133 °C respectively. Synthesized derivatives have better solubility in common organic solvents. Experimentally measured quantum yields (Φ) are in the range of 0.09 to 0.39 in toluene solvent and the molecules exhibit Stokes shifts in the range of 45–100 nm. Density functional theory computations have been performed to explore intramolecular charge transfer property and structure-property relationship of the probes. The novel unsymmetrical benzo[b]thiophene substituted 1,3,4‑oxadiazole derivatives are potential candidates and could play a significant role in organic light-emitting devices (OLED)/optoelectronic applications.

Palladium(0) catalyzed Suzuki cross-coupling reaction of 2,5-dibromo-3-methylthiophene: selectivity, characterization, DFT studies and their biological evaluations

Thiophene derivatives have shown versatile pharmacological activities. The Suzuki reaction proved a convenient method for C–C bond formations in organic molecules. In the present research work novel derivatives of 2,5-dibromo-3-methylthiophene (3a–k and 3l–p) has been synthesized, via Suzuki coupling reaction in low to moderate yields. A wide range of functional groups were well tolerated in reaction. Density functional theory investigations on all synthesized derivatives (3a–3p) were performed in order to explore the structural properties. The pharmaceutical potential of synthesized compounds was investigated through various bioassays (antioxidant, antibacterial, antiurease activities). The compounds 3l, 3g, 3j, showed excellent antioxidant activity (86.0, 82.0, 81.3%), respectively by scavenging DPPH. Synthesized compounds showed promising antibacterial activity against tested strains. 3b, 3k, 3a, 3d and 3j showed potential antiurease activity with 67.7, 64.2, 58.8, 54.7 and 52.1% inhibition at 50 µg/ml. Results indicated that synthesized molecules could be a potential source of pharmaceutical agents.

Efficient Double Suzuki Cross-Coupling Reactions of 2,5-Dibromo-3-hexylthiophene: Anti-Tumor, Haemolytic, Anti-Thrombolytic and Biofilm Inhibition Studies.

The present study describes several novel 2,5-biaryl-3-hexylthiophene derivatives (3a–i) synthesized via a Pd(0)-catalyzed Suzuki cross-coupling reaction in moderate to good yields. The novel compounds were also analyzed for their anti-thrombolytic, haemolytic, and biofilm inhibition activities. In addition, the anti-tumor activity was also evaluated in vitro for newly-synthesized compounds, where 3-hexyl-2,5-bis(4-(methylthio)phenyl)thiophene exhibited the best anti-tumor activity against 4T1 cells with IC50 value of 16 μM. Moreover, 2,5-bis(4-methylphenyl)-3-hexylthiophene showed the highest activity against MCF-7 cells with an IC50 value of 26.2 μM. On the other hand, the compound 2,5-bis(4-chloropheny)-3-hexylthiophene exhibited excellent biofilm inhibition activity. Furthermore, the compound 2,5-bis(3-chloro-4-fluorophenyl)-3-hexylthiophene also exhibited better anti-thrombolytic and hemolytic activity results as compared to the other newly-synthesized compounds.

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.

Palladium (0) catalyzed Suzuki cross-coupling reactions of 2,4-dibromothiophene: selectivity, characterization and biological applications

A series of novel 2-aryl1-4-bromothiophenes (2a–f), biarylthiophenes with non-identical aryl groups (3a–e) and biarylthiophenes with identical aryl groups (4a–f) were synthesized in moderate to excellent yields by using different arylboronic acids in a Suzuki–Miyaura cross-coupling reaction. The experimental results showed that the use of K2CO3 as base resulted in moderate yields compared with that of good yields obtained upon using K3PO4. The highest yield obtained using K3PO4 was 82% for 2, 4-bis (4-chlorophenyl) thiophene (4d). The synthesized compounds in the present study were examined for their biofilm inhibition and hemolysis assay. Among all compounds 2, 4-bis (4-methoxyphenyl) thiophene (4b) was found to strongly inhibit the formation of bacterial biofilm against E. coli. The compound 4b exhibited higher inhibition (80.92%) compared with the standard Rifampicin with 97.43% inhibition. The compound 2, 4-bis (4-chlorophenyl) thiophene (4d) displayed strong anti-biofilm activity with its ability to prevent the formation of Pasteurell amultocida biofilm at the percent inhibition of 74.53%. In addition, 2f showed the highest percentage hemolysis 16.0% compared with that of the standard Triton-X-100. 3

Trace amount CuII (ppm) and mixture design of CuII/PdII catalyzed Suzuki cross-coupling reactions based on the cooperative interaction of metal with a conjugated pyridylspirobifluorene

The multilayers of PEI-(Cu/psf)n could be capable of gradually discharging highly active catalytic moieties to promote the C–C coupling reactions with ultra low Cu-loadings of 1.4 × 10−5 mol%.

Regioselective synthesis of 2-(bromomethyl)-5-aryl-thiophene derivatives via palladium (0) catalyzed suzuki cross-coupling reactions: as antithrombotic and haemolytically active molecules.

BackgroundIt is seen that the regioselective functionalizations of halogenated heterocycles play an important role in the synthesis of several types of organic compounds. In this domain, the Suzuki-Miyaura reaction has emerged as a convenient way to build carbon-carbon bonds in synthesizing organic compounds. Some of the most important applications of these reactions can be seen in the synthesis of natural products, and in designing targeted pharmaceutical compounds. Herein, we present the regioselective synthesis of the novel series of 2-(bromomethyl)-5-aryl-thiophenes 3a-i,via Suzuki cross-coupling reactions of various aryl boronic acids with 2-bromo-5-(bromomethyl)thiophene (2).ResultsThe synthesized compounds were screened for their haemolytic and antithrombolytic activities. The novel compounds 3f, 3i showed highest 69.7, 33.6% haemolysis of blood cells, respectively. The antithrombolytic activity of the compounds was found to be within low to moderate against human blood clot. The compound 3i showed potent clot lysis (31.5%).ConclusionsConsidering these results, it is concluded that the synthesized compounds can be used as a promising source of therapeutic agents.

Cucurbit[7]uril promoting PdCl2-catalyzed cross-coupling reaction of benzyl halides and arylboronic acids in aqueous media

The research provides a novel approach for producing diarylmethane derivatives using CB[7]–NaCl–PdCl2 catalyzed Suzuki cross-coupling reaction of benzyl chloride derivatives and arylboronic acids in ethanol aqueous solution.