Mizoroki Heck Cross-coupling Reactions Research Articles

Dual photoredox/nickel-catalyzed Mizoroki–Heck cross-coupling reactions

A method for the Mizoroki–Heck reaction of electron-deficient olefins acrylates with aryl bromides to obtain α-arylation products of acrylates via a dual light/nickel catalytic system is described. This transformation features a broad substrate scope, good functional group tolerance.

Furaldehyde-based magnetic supported palladium nanoparticles as an efficient heterogeneous catalyst for Mizoroki–Heck cross-coupling reaction

Novel furaldehyde-based magnetic nanoparticles are used as an efficient catalyst for the Mizoroki–Heck reaction of arylhalide and olefins.

Improved Process for the Synthesis of 3-(3-Trifluoromethylphenyl)propanal for More Sustainable Production of Cinacalcet HCl.

Cinacalcet (I), sold as hydrochloride salt, is a calcimimetic drug which has been approved for the treatment of secondary hyperparathyroidism in patients with chronic renal disease and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Here, an improved method for the synthesis of 3-(3-trifluoromethylphenyl)propanal (II), a key intermediate for the preparation of I, is described. The protocol required a Mizoroki-Heck cross-coupling reaction between 1-bromo-3-(trifluoromethyl)benzene and acroleine diethyl acetal, catalyzed by Pd(OAc)2 in the presence of nBu4NOAc (tetrabutylammonium acetate), followed by the hydrogenation reaction of the crude mixture of products in a cascade process. Palladium species, at the end of the reaction, were efficiently recovered as Pd/Al2O3. The procedure was developed under conventional heating conditions as well as under microwave-assisted conditions. The obtained mixture of 1-(3,3-diethoxypropyl)-3-(trifluoromethyl)benzene (III), impure for ethyl 3-(3-trifluoromethylphenyl) propanoate (IV), was finally treated, under mild conditions, with potassium diisobutyl-tert-butoxyaluminum hydride (PDBBA) to obtain after hydrolysis 3-(3-trifluoromethylphenyl)propanal (II), in an excellent overall yield and very high purity. Microwave conditions permitted a reduction in reaction times without affecting selectivity and yield. The final API was obtained through reductive amination of (II) with (R)-(+)-1-(1-naphthyl)ethylamine (V) using a catalyst prepared by us with a very low content of precious metal.

Biomacromolecule supported N-heterocyclic carbene-palladium(II) as a novel catalyst for Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions

Biomacromolecule supported N-heterocyclic carbene-palladium(II) as a novel catalyst for Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions

Palladium CNC-pincer complex supported on magnetic nanospindles as a highly efficient and recyclable nanocatalyst in Mizoroki–Heck cross-coupling and reduction of nitroarenes

Fe3O4 nanospindles were synthesized through the hydrothermal method followed by thermal treatment. The composite of Fe3O4@SiO2 core–shell nanospindles was synthesized by the Stuber process via the hydrolysis of tetraethyl orthosilicate (TEOS) in the presence of Fe3O4 nanospindles. Palladium triazine‐bridged bisimidazolium pincer complex was successfully supported on Fe3O4@SiO2 core–shell nanospindles. The magnetic nanospindles‐supported palladium CNC-pincer complex was used as a practical and recyclable catalyst in the Mizoroki–Heck cross-coupling reaction and reduction of nitroarenes.

Synthesis, characterization, Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions of Schiff base-Pd(II) complexes

Cross-coupling reactions are powerful and versatile tools mainly for the formation of carbon-carbon bonds in modern organic synthesis. The cross-coupling reactions catalyzed by palladium complexes have attracted a great deal of attention of researchers in recent years. Two new mononuclear Schiff base-Pd(II) complexes (1, 2) were synthesized and characterized by FT-IR, UV–Vis, NMR (1H and 13C), ESI-MS, CHNS analysis, magnetic susceptibility, molar conductivity, melting points, thermogravimetric analysis in addition to powder X-ray diffraction and SEM-EDX analysis. Depending on spectral and magnetic measurements, the suggested geometrical shapes of these complexes were reported. Further, Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions, using K2CO3 as base and Et-OH+H2O (1:2) ration as solvent under atmospheric conditions, were carried out with the synthesized complexes in the presence of various aryl halides, phenylboronic acid, and styrene. Schiff base-Pd(II) complexes (1, 2) were found to provide very good yields in Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions. The results showed that electron-donating and electron-withdrawing substituents on the aryl halides might produce coupling products in perfect yield in the presence of Pd(II) complexes 1 and 2.

Catalysis of a Bis-Caffeine Palladium(II) NHC-Pincer Complex

A tridentate bis-NHC Pd complex, based on caffeine, was studied for its catalytic activity. This complex displayed a high catalytic activity in the Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions of aryl halides. The Sonogashira cross-coupling was also investigated but reveals a fast plateauing of the reaction. Aryl iodides as well as aryl bromides react when equipped with either electron-donating or electron-withdrawing substituents. Aryl chlorides, which contained electron-withdrawing groups, were also reactive under the applied conditions.

The Mizoroki-Heck reaction between in situ generated alkenes and aryl halides: cross-coupling route to substituted olefins.

This review covers palladium-catalyzed typical Mizoroki-Heck cross-coupling reactions of aryl halides with in situ generated alkenes, by following a typical Heck coupling mechanism to form substituted olefins unlike direct cross-coupling of alkenes with aryl halides in Heck olefination. These reactions solve the issue of alkenes undergoing polymerization at high temperatures and increase reaction efficiency by reducing the reaction time and purification steps.

Boosting the activity of Mizoroki-Heck cross-coupling reactions with a supramolecular palladium catalyst favouring remote Zn⋯pyridine interactions.

Transition metal catalysis benefitting from supramolecular interactions in the secondary coordination sphere in order to pre-organize substrates around the active site and reach a specific selectivity typically occurs under long reaction times and mild reaction temperatures with the aim to maximize such subtle effects. Herein, we demonstrate that the kinetically labile Zn⋯N interaction between a pyridine substrate and a zinc-porphyrin site serving for substrate binding is a unique type of weak interaction that enables identification of supramolecular effects in transition metal catalysis after one hour at a high reaction temperature of 130 °C. Under carefully selected reaction conditions, supramolecularly-regulated palladium-catalyzed Mizoroki-Heck reactions between 3-bromopyridine and terminal olefins (acrylates or styrenes) proceeded in a more efficient manner compared to the non-supramolecular version. The supramolecular catalysis developed here also displayed interesting substrate-selectivity patterns.

AIEE active stilbene based fluorescent sensor with red-shifted emission for vapor phase detection of nitrobenzene and moisture sensing

A unique π-electron rich stilbene-based sensor with significantly enhanced red-shifted fluorescence emission has been synthesized via a Mizoroki-Heck cross-coupling reaction. The strong fluorescence properties of stilbene derivative as a potential fluorescent sensor have been investigated for sensitive and selective detection of hazardous and threatening nitrobenzene (NB) in both solution and vapor phase. The fluorescence emission intensity of stilbene sensor 1 at 474 nm was quenched upon interaction with NB. The fluorescence quenching was attributed to the combined effect of dominant smaller and adjustable size of NB and photo-induced electron transfer (PET) process. Stilbene sensor 1 is the first active bathochromic shifted fluorescent sensor with AIEE property was developed for both solution and vapor phase detection of NB. Possible interactions of stilbene sensor 1 with NB was evaluated by UV–vis., fluorescence, density functional theory (DFT) calculations, and 1H NMR titration experiment. Additionally, non-covalent interaction (NCI), Frontier molecular orbitals (FMOs) and interaction energy were studied by using Gaussian 09 software. Moreover, test strips were fabricated to accomplish contact mode detection of NB. Further, stilbene sensor 1 was successfully applied for trace detection of NB in real water samples.

Synthesis of Pd+2 complexes of Schiff bases containing methyl 2-amino-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate and spectral and catalytic activities

Here in, ONS-donor atom containing Schiff base ligands (1, 2) was used to prepare 1a and 2a complexes. The Schiff base ligands were synthesized using 2...hydroxy-3-methoxybenzaldehyde and 4-benzoxybenzaldehyde with methyl 2-amino-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate as precursors in ethanol medium. Pd(II) complexes (1a, 2a) were prepared using the corresponding [PdCl2(CH3CN)2] and Schiff base in a (1:1) molar proportion. The Schiff bases (1, 2) and their Pd(II) complexes (1a, 2a) were then identified via various analytical/spectroscopic methods (1H and 13C) NMR, UV- Vis spectra, FT-IR, mass, TGA and CHNS to determine their molecular structures. Finally, the results obtained based on Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions show that electron-donating and electron-withdrawing substituents on the aryl halide might produce coupling products in excellent yield in the presence of 1a, 2a complexes (as catalysts) under optimum conditions.

Tailor-Made POLITAG-Pd0 Catalyst for the Low-Loading Mizoroki–Heck Reaction in γ-Valerolactone as a Safe Reaction Medium

In this contribution, we have reported our study on the fine-tuned design and synthesis of new POLITAGs-Pd0 (POLymeric Ionic TAG) catalytic systems with the intention of defining highly efficient heterogeneous palladium catalysts stabilized by ionic tags able to operate at a very low loading while being fully recoverable/reusable. By varying both the support and the ratio between the metal and immobilized ionic tag, we have accessed five different heterogeneous catalytic systems that have been fully characterized (EA, XPS, TEM, and HR-TEM) to investigate their morphological differences. The catalytic efficiency of the newly prepared POLITAGs-Pd0 materials was then tested and compared in the representative Mizoroki–Heck cross-coupling reaction, a universally investigated and widely useful process. A close correlation between the catalyst support and catalytic performances has been highlighted. The best system POLITAG-Pd0-HM features a high TOF value (26,786 h–1), affording the final products in high isolated yields by using as little as only 0.0007 mol % of Pd. Moreover, this high catalytic activity coupled with the use of γ-valerolactone (GVL) as a green reaction medium has led to the definition of a very efficient waste-minimized protocol. The newly designed catalyst has been utilized in the representative synthesis of Amiloxate, a widely used sunscreen agent, that could be prepared with negligible metal contamination and very low E-factor.

Magnetically recyclable Schiff-based palladium nanocatalyst [Fe3O4@SiNSB-Pd] and its catalytic applications in Heck reaction

A magnetically separable palladium nanocatalyst has been synthesized through the immobilization of palladium onto 3-aminopropylphenanthroline Schiff based functionalized silica coated superparamagnetic Fe 3 O 4 nanoparticles. The nanocatalyst ( Fe 3 O 4 @SiNSB-Pd ) was fully characterized using several spectroscopic techniques, such as FT-IR, HR-SEM, TEM, XRD, ICP, and XPS. The microscopic image of Fe 3 O 4 showed spherical shape morphology and had an average size of 150 nm. The Pd-nanoparticles exhibited an average size 3.5 ± 0.6 nm. The successful functionalization of Fe 3 O 4 @SiNSB-Pd was identified by FT-IR spectroscopy and the appearance of palladium species in Fe 3 O 4 @SiNSB-Pd was confirmed by XRD analysis. While XPS has been utilized for the determination of the chemical oxidation state of palladium species in Fe 3 O 4 @SiNSB-Pd . Several activated and deactivated arene halides and olefines were employed for Mizoroki-Heck cross-coupling reactions in the presence of Fe 3 O 4 @SiNSB-Pd , each of which produced the respective cross-coupling products with excellent yields. The Fe 3 O 4 @SiNSB-Pd shows good reactivity and reusability for up to seven consecutive cycles.

Pyrene Functionalized Highly Reduced Graphene Oxide-palladium Nanocomposite: A Novel Catalyst for the Mizoroki-Heck Reaction in Water.

The formation of a C-C bond through Mizoroki-Heck cross-coupling reactions in water with efficient heterogeneous catalysts is a challenging task. In this current study, a highly reduced graphene oxide (HRG) immobilized palladium (Pd) nanoparticle based catalyst (HRG-Py-Pd) is used to catalyze Mizoroki-Heck cross-coupling reactions in water. During the preparation of the catalyst, amino pyrene is used as a smart functionalizing ligand, which offered chemically specific binding sites for the effective and homogeneous nucleation of Pd NPs on the surface of HRG, which significantly enhanced the physical stability and dispersibility of the resulting catalyst in an aqueous medium. Microscopic analysis of the catalyst revealed a uniform distribution of ultrafine Pd NPs on a solid support. The catalytic properties of HRG-Py-Pd are tested towards the Mizoroki-Heck cross-coupling reactions of various aryl halides with acrylic acid in an aqueous medium. Furthermore, the catalytic efficacy of HRG-Py-Pd is also compared with its non-functionalized counterparts such as HRG-Pd and pristine Pd NPs (Pd-NPs). Using the HRG-Py-Pd nanocatalyst, the highest conversion of 99% is achieved in the coupling reaction of 4-bromoanisol and acrylic acid in an aqueous solution in a relatively short period of time (3 h), with less quantity of catalyst (3 mg). Comparatively, pristine Pd NPs delivered lower conversion (∼92%) for the same reaction required a long reaction time and a large amount of catalyst (5.3 mg). Indeed, the conversion of the reaction further decreased to just 40% when 3 mg of Pd-NPs was used which was sufficient to produce 99% conversion in the case of HRG-Py-Pd. On the other hand, HRG-Pd did not deliver any conversion and was ineffective even after using a high amount of catalyst and a longer reaction time. The inability of the HRG-Pd to promote coupling reactions can be attributed to the agglomeration of Pd NPs which reduced the dispersion quality of the catalyst in water. Therefore, the high aqueous stability of HRG-Py-Pd due to smart functionalization can be utilized to perform other organic transformations in water which was otherwise not possible.

Pd(II)-Schiff base complexes: Synthesis, characterization, Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions, enzyme inhibition and antioxidant activities

In this study, new coordination complexes (1a-1e) of Pd(II) with Schiff base ligands were synthesized and characterized by elemental analysis, magnetic susceptibility, molar conductivity, FT-IR, 1H–13C NMR spectroscopy, UV–vis spectroscopy, and mass spectrometry techniques. The ligands formed only 1:2 complexes with the Pd(II) except for the complex 1e. The thermal analysis of the complexes was performed by the TGA technique. The antioxidant potential, enzyme inhibition activity, and catalytic properties of the complexes were investigated as well. The Pd(II) complexes 1b and 1c indicated the best catalytic activity with 62.63% and 61.05% selectivity in the conversions of 82.61% and 87.84%. The in vitro antioxidant activity showed that the Pd(II) complexes, particularly 1a and 1e have effective antioxidant activities. According to the enzyme activity analyses, complex 1b (IC50 value 69.3 ± 5.2 μM) showed the most effective pancreatic lipase inhibition, whereas complex 1e (IC50 value 25.7 ± 3.2 μM) had the most effective tyrosinase inhibition among the synthesized compounds. Overall, the present paper discusses the synthesis, characterization and catalytic activities of various novel Pd(II)-Schiff base complexes with their antioxidant potentials, pancreatic lipase and tyrosinase inhibitory activities.

Synthesis, photophysical properties and catalytic activity of Ƙ3-SCS pincer palladium (II) complex of N,N'-di-tert-butylbenzene-1,3-dicarbothioamide supported by DFT analysis

The title complex [PdCl(L)] (1), is obtained from the reaction of SCS pincer ligand HL (where, HL = N,N'-di-tert-butylbenzene-1,3-dicarbothioamide) with lithium tetrachloropalladate (II) in methanol. The compound 1 is characterized by elemental analysis, FTIR, 1H, and 13C NMR spectroscopy, UV–Vis spectroscopy, and X-ray crystallographic techniques. At room temperature, 1 emits luminescence light of wavelength 460 nm in the solid state upon excitation by UV light of wavelength 280 nm. The average emission lifetime indicates that, both the ligand and complex emission is fluorescence in nature and involves mainly ligand centers π-π* deexcitation. It also shows good catalytic activity towards Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions of aryl bromides with tert-butyl acrylate and p-tolylboronic acid respectively. For both type of reactions, >99% conversion of the substrates is found to occur for electronically activated p-nitro bromobenzene using 1 mol % of 1. Further, modern DFT calculations are performed to decipher the mechanistic insight on the preferable pathways of the Mizoroki-Heck cross-coupling reaction. Stepwise free energy of reactions for various probable reaction pathways suggest that the catalytic route has profound preference for Pd(0)-Pd(II) over Pd(II)-Pd(IV) pathway.

Synthesis, crystal structure, and catalytic activity of bridged-bis(N-heterocyclic carbene) palladium(II) complexes in selective Mizoroki-Heck cross-coupling reactions

A series of three 1,3-propanediyl bridged bis(N-heterocyclic carbene)palladium(II) complexes (Pd-BNH1, Pd-BNH2, and Pd-BNH3), with + I effect order of the N-substituents of the ligand (isopropyl > benzyl > methoxyphenyl), was the subject of a spectroscopic, structural, computational and catalytic investigation. The bis(NHC)PdBr2 complexes were evaluated in Mizoroki-Heck coupling reactions of aryl bromides with styrene or acrylate derivatives and showed high catalytic efficiency to produce diarylethenes and cinnamic acid derivatives. The X-ray structure of the most active palladium complex Pd-BNH3 shows that the Pd(II) center is bonded to the two carbon atoms of the bis(N-heterocyclic carbene) and two bromide ligands in cis position, resulting in a distorted square planar geometry. The NMR data of Pd-BNH3 are consistent with a single chair-boat rigid conformer in solution with no dynamic behavior of the 8-membered ring palladacycle in the temperature range 25–120 °C. The catalytic activities of three Pd-bridged bis(NHC) complexes in the Mizoroki-Heck cross-coupling reactions were not found to have a direct correlation with +I effect order of the N-substituents of the ligand. However, a direct correlation was found between the DFT calculated absolute softness of the three complexes with their respective catalytic activity. The highest calculated softness, in the case of Pd-BNH3, is expected to favor the coordination steps of both the soft aryl bromides and alkenes in the Heck catalytic cycle.

Ferrocenylimine Palladium (II) Complexes: Synthesis, Characterization and Application in Mizoroki-Heck and Suzuki-Miyaura Cross-Coupling Reactions

Carbon-carbon cross-coupling reactions are essential synthetic tools for synthesizing polymers, natural products, agrochemicals, and pharmaceuticals. Therefore, new catalysts that function with greater efficiency and functional group tolerance are being researched. We have prepared new ferrocenylimine monodentate N and P donor ligands and N^N and N^P bidentate chelating ligands (L1 to L4) employed in stabilizing palladium ions for application in Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions. The ferrocenylimine ligands were successfully synthesized by Schiff base condensation reactions of acetyl ferrocene with hydrazine monohydrate to afford ferrocenyl hydrazone (L1). Ligand L1 was further treated with aldehydes to give ferrocenyl(2-diphenylphosphino)imine (L3) and ferrocenyl(pyridyl)imine (L3), while phosphination of L1 with chlorodiphenylphosphine afforded L2. The ligands were used to prepare new palladium(II) complexes (C1 to C4) by complexation with [PdCl2(MeCN)2]. All the ligands and complexes were fully characterized using standard spectroscopic and analytical techniques, including 1H NMR and 13C NMR spectroscopy, FT-IR spectroscopy, mass spectrometry and elemental analysis. The complexes (C1 to C4) were tested for efficacies in catalyzing Mizoroki-Heck and Suzuki-Miyaura C-C cross-coupling reactions and proved to be suitable catalyst precursors. Ferrocenyl(2-diphenylphosphine)imino and ferrocenyl-methyl hydrazone palladium(II) complexes C2 and C3 showed the best activities at TONs of up to 201. The ferrocenyl palladium(II) (pre)catalysts demonstrated moderate activity in Mizoroki-Heck reactions involving substrates with substituents on the olefin and aryl halide (including 4-Cl, 4-CH3, -CO2Me and -CO2Et). Density Functional Theory was used to study the mechanism of the Mizoroki-Heck cross-coupling reactions and have led to confirmation of the widely accepted catalytic cycle. Catalyst precursors (C1 to C4) also displayed good activity and selectivity in Suzuki-Miyaura cross-coupling reactions, at 0.5 mol% catalyst loading, with good tolerance to functional groups present on the aryl halide and boronic acid substrates (such as 4-Cl, 4-CHO, 4-COOH, 3-NO2, 3,5-dimethoxy and 4-CH3).

Facile Synthesis and Characterization of Palladium@Carbon Catalyst for the Suzuki-Miyaura and Mizoroki-Heck Coupling Reactions

Palladium-based carbon catalysts (Pd/C) can be potentially applied as an efficient catalyst for Suzuki–Miyaura and Mizoroki–Heck coupling reactions. Herein, a variety of catalysts of palladium on activated carbon were prepared by varying the content of ‘Pd’ via an in situ reduction method, using hydrogen as a reducing agent. The as-prepared catalysts (0.5 wt % Pd/C, 1 wt % Pd/C, 2 wt % Pd/C and 3 wt % Pd/C) were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Brunauer–Emmett–Teller (BET) analyses. The catalysts were tested as a coupling catalyst for Suzuki–Miyaura coupling reactions involving aryl halides and phenyl boronic acid. The optimization of the catalyst by varying the palladium content on the activated carbon yielded Pd/C catalysts with very high catalytic activity for Suzuki reactions of aryl halides and a Mizoroki–Heck cross-coupling reaction of 4-bromoanisol and acrylic acid in an aqueous medium. A high ‘Pd’ content and uniform ‘Pd’ impregnation significantly affected the activity of the catalysts. The catalytic activity of 3% Pd/C was found to make it a more efficient catalyst when compared with the other synthesized Pd/C catalysts. Furthermore, the catalyst reusability was also tested for Suzuki reactions by repeatedly performing the same reaction using the recovered catalyst. The 3% Pd/C catalyst displayed better reusability even after several reactions.

A new PEPPSI type N-heterocyclic carbene palladium(II) complexes and its efficiency as a catalyst for Mizoroki-Heck cross-coupling reactions in water : Synthesis, Characterization and their antimicrobial and Cytotoxic activities

A series of novel benzimidazolium salts 2 and their new air and moisture stable PEPPSI type N-heterocyclic carbene palladium(II) complexes (PEPPSI: pyridine-enhanced pre-catalyst preparation, stabilisation, and initiation), were synthesized and characterized by means of 1H and 13C{1H} NMR, FTIR spectroscopic methods and elemental analysis was employed to catalyze the Mizoroki-Heck cross-coupling reactions of aryl bromides with styrene in water. To the best of our knowledge, this is the first report where a Pd-PEPPSI catalyst was successfully employed in aqueous-phase Mizoroki-Heck reaction. Good to excellent yields of cross-coupling products were obtained with a range of representative aryl bromides under relatively mild conditions. Moreever the antimicrobial activity of the PEPPSI type N-heterocyclic carbene palladium(II) complexes 3a-e varies with the nature of the ligands. Also, the IC50 values of both, complexes (3a-e) have been determined. In addition, the new PEPPSI type N-heterocyclic carbene palladium(II) complexes were screened for their cytotoxic activities. Complex 3b exhibited the highest antitumor effect with IC50 values 0.63 μg/mL and against MCF-7.