Heck Reaction Research Articles

Substituted indeno[2,1‐c]fluorene‐5,8‐diones as a platform for synthesis of polyaromatic hydrocarbons possessing extended π‐conjugated systems with butterfly‐like frameworks

Synthetic options for conversion of indeno[2,1‐c]fluorene‐5,8‐diones into larger polyaromatic compounds with extended π‐conjugated systems were explored. The crucial two‐fold transformation of the five‐membered ketone moieties of indeno[2,1‐c]fluorene‐5,8‐diones was based either on a one‐carbon homologation or on a ring‐expansion reaction which eventually enabled syntheses of compounds possessing substituted tribenzo[a,e,l]indeno[1,2,3‐hi]acephenanthrylenes and [5]helicenes scaffolds. The former was prepared by using a reaction sequence based on Ramirez olefination, intramolecular Heck reaction, and intermolecular Suzuki‐Miyaura cross‐coupling, whereas the latter utilized a sequence comprising Büchner−Curtius−Schlotterbeck reaction and intermolecular Suzuki‐Miyaura cross‐coupling. Scholl reaction of selected [5]helicenes yielded planarized polyaromatic compounds with the tribenzo[a,e,l]indeno[1,2,3‐hi]acephenanthrylene scaffold. Where possible, structures of products were confirmed by X‐ray diffraction analyses. Photophysical properties were determined as well.

Synthesis and photodynamic activity of new 5-[(E)-2-(3-alkoxy-1-phenyl-1H-pyrazol-4-yl)ethenyl]-2-phenyl-3H-indoles.

A series of new indole-pyrazole hybrids 8a-m were synthesized through the palladium-catalyzed ligandless Heck coupling reaction from easily accessible unsubstituted, methoxy- or fluoro-substituted 4-ethenyl-1H-pyrazoles and 5-bromo-3H-indoles. These compounds exerted cytotoxicity to melanoma G361 cells when irradiated with blue light (414 nm) and no cytotoxicity in the dark at concentrations up to 10 µM, prompting us to explore their photodynamic effects. The photodynamic properties of the example compound 8d were further investigated in breast cancer MCF-7 cells. Evaluation revealed comparable anticancer activities of 8d in both breast and melanoma cancer cell lines within the submicromolar range. The treatment induced a massive generation of reactive oxygen species, leading to different types of cell death depending on the compound concentration and the irradiation intensity.

Deconvoluting Substrates, Support, and Temperature Effects on Leaching and Deactivation of Pd Catalysts: An In Situ Study in Flow.

Leaching behavior of three different Pd heterogeneous catalysts (PdEnCat 30, FibreCat FC1001, and Pd/Al2O3) during the Heck reaction of iodobenzene and methyl acrylate, in the presence of triethylamine, was compared using a tandem flow reactor. While leaching was observed in all three cases, Pd/Al2O3 appeared to be the most robust, showing little/no leaching at ambient temperature. The leached Pd species also appear to display different catalytic activities. With a slight modification of the reactor, the leaching caused by individual components of the reaction mixture can be assessed separately. For the polymer-supported catalysts, triethylamine caused the largest amount of leaching, even at 30 °C. In contrast, the leaching from Pd/Al2O3 was observed only in the presence of iodobenzene at 90 °C. Variations in leaching behavior were ascribed to differences in Pd species and immobilization methods.

1,4-Pd Migration-Enabled Synthesis of Fused 4-Membered Rings.

1,4-Palladium migration has been widely used for the functionalization of remote C-H bonds. However, this mechanism has been limited to aryl halide precursors. This work reports an unprecedented Pd0-catalyzed cyclobutanation protocol producing valuable fused cyclobutanes starting from cycloalkenyl (pseudo)halides. This reaction takes place via alkenyl-to-alkyl 1,4-Pd migration, followed by intramolecular Heck coupling. The method performs best with cyclohexenyl precursors, giving access to a variety of substituted bicyclo[4,2,0]octenes. Reactants containing an N-methyl or methoxy group give rise to fused azetidines or oxetanes, respectively, via the same mechanism. Kinetic and deuterium-labeling studies point to a rate-limiting C(sp3)-H activation step.

Construction of Benzofuran‐3(2H)‐one Scaffolds bearing a C2 Quaternary Center via Palladium‐Catalyzed Carbonylative Heck Reaction using Mo(CO)6 as Carbonyl Source

A Pd‐catalyzed carbonylative Heck reaction of 2‐iodophenyl alkenyl ether using Mo(CO)6 as a safe CO source has been developed. This research provides an atom‐economic and straightforward route for the efficient construction of benzofuran‐3(2H)‐one scaffolds with a C2 quaternary center in moderate to good yields, which features operational safety, good functional group compatibility and easy scale‐up.

Enantioselective Construction of Anthracenylidene-Based Axial Chirality by Asymmetric Heck Reaction.

Anthracenylidene is an intriguing structural unit with potential in various fields. The study presents a novel approach to introducing axial chirality into this all-carbon core skeleton through a remotely controlled desymmetrization strategy. A palladium-catalyzed enantioselective Heck arylation of exocyclic double bond of anthracene with two distinct substituents at the C10 position is harnessed to realize such a transformation. The judicious identification of the P-centrally chiral ligand is pivotal to ensure the competitive competence in reactivity and stereocontrol when the heteroatom handle is absent from the anthracenylidene skeleton. Both C10 mono- and disubstituted substrates were compatible for the established catalytic system, and structurally diverse anthracenylidene-based frameworks were forged with good-to-high enantiocontrol. The subsequent derivatization of the obtained products yielded a valuable array of centrally and axially chiral molecules, thus emphasizing the practicality of this chemistry. DFT calculations shed light on the catalytic mechanism and provided insights into the origin of the experimentally observed enantioselectivity for this reaction.

Silica gel-supported Pd nanocatalyst: Efficient Mizoroki-Heck reactions and sustainable Ozagrel synthesis

We developed a cost-effective silica gel-supported palladium nanocatalyst in a three-step reactions process. Initially, silica gel (60–120 mesh) underwent amino group functionalization using 3-aminopropyltriethoxysilane, leading to the formation of a Schiff base through a reaction with the 1,10-phenanthroline-2,9-dicarboxaldehyde ligand. Subsequently, palladium nanocatalyst was introduced to the silica matrix ligand in the presence of palladium salt and hydrazine hydrate, resulting in the formation of the silica gel-supported Schiff-base palladium nanocatalyst (Si@SBPdNPs 3). Successful functionalization of the silica matrix was confirmed using various spectroscopic techniques. FT-IR spectra demonstrated the incorporation of organic moieties onto the silica surface, while SEM images revealed the modified spherical shape of the silica gel. TEM and XRD analyses confirmed the presence of palladium on the silica matrix. ICP and EDX measurements validated the anchoring of 0.55 mmol/g of palladium to the catalyst. Additionally, XPS analysis showed the complexation of Pd(0) with the organic ligand on the silica matrix, confirming the successful integration of palladium into the system. This nanocatalyst demonstrated outstanding performance in Mizoroki-Heck reactions, yielding high product outputs in the cross-coupling of various aryl halides and olefins under mild conditions. Additionally, the nanocatalyst was effectively utilized in synthesizing Ozagrel, a thromboxane A2 synthesis inhibitor used for treating noncardioembolic stroke patients. Remarkably, the catalyst demonstrated excellent reusability, maintaining high productivity across five consecutive cycles, underscoring its economic and sustainable potential for industrial applications.

Designing strategically functionalized hybrid porous polymers with octavinylsilsesquioxane/dibenzo[g,p]chrysene/benzo[c]-1,2,5-thiadiazole units for rapid removal of Rhodamine B dye from water

Because of their large surface area and persistent pores that have exceptional adsorption capabilities, porous organic/inorganic polymers (POIPs) with octavinylsilsesquioxane (OVS) units have attracted much interest recently. In this study aimed at removing Rhodamine B (RhB) from wastewater, we utilized OVS nanoparticles synthesized through the Heck coupling process to produce two distinct types: OVS-DBC-PO and OVS-DBC-BT POIPs. OVS and a variety of chemical compounds containing Br, such as tetrabromodibenzo[g,p]chrysene (DBC-Br4), 2,6-bis(4-bromophenyl)pyridine 1-oxide (PO-Br2), and 4,7-dibromobenzo[c][1,2,5]thiadiazole (BT-Br2) were involved in the reactions. Thermogravimetric analysis (TGA) results revealed that the high thermal decomposition temperature (Td10) of OVS-DBC-PO and OVS-DBC-BT POIPs were 447 °C and 543 °C, respectively. Additionally, the OVS-POIPs demonstrated significant porosity, with the OVS-DBC-BT POIP exhibiting the highest specific BET surface area (SABET) of 386 m2 g−1. OVS-DBC-PO and OVS-DBC-BT POIPs exhibit exceptional porosity character. Based on dye adsorption measurements, RhB interacts with functional groups on the OVS-POIP samples' surface and penetrates their pores, enhancing the number of contact sites and the effectiveness of adsorption. Both OVS-DBC-PO and OVS-DBC-BT POIPs demonstrated maximum adsorption capacities of 65 and 66 mg g−1, respectively, at a pH of 4 and a temperature of 25 °C. As a result, OVS-DBC-PO and OVS-DBC-BT POIP materials could be viewed as efficient absorbents for removing RhB from aqueous solutions and this study presents a novel way of making POIPs, which are adsorbents used in the filtration and treatment of water.

Catalytic asymmetric desymmetrization of 1,4-cyclohexadienes for the synthesis of chiral quinolinone derivatives

Quinolinone is a prevalent nitrogen-containing heterocycle in organic and pharmaceutical chemistry. In this report, we developed an intramolecular catalytic asymmetric Heck reaction of symmetrical 1,4-cyclohexadiene to construct quinolinone derivatives. The Pd(OAc)2/(R)-BINAP catalytic system enabled a series of quinolinone analogs containing two consecutive chiral centers to be obtained with up to 76% yield and 95% ee. Meanwhile, the synthesis of quinolinones bearing an all-carbon quaternary center and three consecutive chiral centers was also achieved in 85% ee via PdCl2/(R)-BoPhoz catalyzed intramolecular asymmetric Heck/alkylation reaction.

Study of size effect of palladium atoms as single-atom and clusters nanoparticle catalysts for Heck reactions

We reported a series of nitrogen-doped carbon-supported palladium (Pd) species with various sizes for the Heck reaction of iodobenzene and methyl acrylate. By precisely controlling the synthesis procedure, we have successfully synthesized a range of Pd-based catalysts, including single Pd atom, sub-nanometer Pd clusters (∼ 0.4 nm, and ∼1.6 nm), and Pd nanoparticles (∼5.8 nm and 10 nm). Remarkably, these catalysts exhibit a distinct size-dependent catalytic activity in the Heck reaction. In the case of the Heck reaction of 4‑methoxy-iodobenzene and methyl acrylate, the Pd-10 site demonstrated the highest site-specific turnover frequency (TOF), reaching 792.5 h−1. This performance is impressively 5.2 and 15.6 times superior to that of the Pd1 site (152 h-1) and Pd-10 site (50.6 h-1), respectively. Significantly better in the Heck reactions with other aryl halides were achieved with Pd-1.6/N-C (comprising of approximately 1.6 nm-sized Pd clusters), compared to those containing 10 nm-sized nanoparticles (Pd-10/N-C) or Pd1/N-C. These findings suggested that Pd clusters of around 1.6 nm may serve as the potential catalytic sites for the Heck reaction.

Synthesis and Characterization of New Bases Derived from Nitrophenylpyrazoles, Coordination to Palladium and Antifungal Activity and Catalytic Activity in Mizoroki–Heck Reactions

In this study, we report the synthesis of eight Schiff bases (3–10) type N-heterocycle (N-het) using conventional refluxing conditions as well as different eco-friendly techniques such as grinding, thermal fusion, microwave irradiation (MWI) and ultrasound, all of them in the presence of a catalytic amount of acetic acid. These procedures had the additional advantage of being environmentally friendly and high-yield, making these protocols an alternative for Schiff-base syntheses. The obtained Schiff bases were coordinated to palladium, generating new complexes of type [Pd2Cl4(N-het)2]. Complexes [Pd2Cl4(5)2] and [Pd2Cl4(9)2] showed high activity and selectivity for a model Mizoroki–Heck C-C coupling reaction of styrene with iodobenzene and bromobenzaldehydes. All compounds and complexes were evaluated for antifungal activity against clinically important fungi such as Candida albicans and Cryptococcus neoformans. Although the Schiff bases (3–10) showed low antifungal activity against both fungi, some of their palladium complexes such as [Pd2Cl4(3)2], [Pd2Cl4(5)2], [Pd2Cl4(8)2] and [Pd2Cl4(10)2] showed comparatively higher antifungal effects mainly against C. neoformans. The product of the Mizoroki–Heck-type C-C coupling reactions, 4-styrylbenzaldehyde, was isolated and purified to be later used in the synthesis of four new nitrophenylpyrazole derivatives of styrylimine, which also displayed antifungal activity, especially against C. neoformans.

Photochemical Skeletal Editing of Pyridines to Bicyclic Pyrazolines and Pyrazoles.

We present an efficient one-pot photochemical skeletal editing protocol for the transformation of pyridines into diverse bicyclic pyrazolines and pyrazoles under mild conditions. The method requires no metals, photocatalysts, or additives and allows for the selective removal of specific carbon atoms from pyridines, allowing for unprecedented versatility. Our approach offers a convenient and efficient means for the late-stage modification of complex drug molecules by replacing the core pyridine skeleton. Moreover, we have successfully scaled up this procedure in stop-flow and flow-chemistry systems, showcasing its applicability to intricate transformations such as the Diels-Alder reaction, hydrogenation, [3 + 2] cycloaddition, and Heck reaction. Through control experiments and DFT calculations, we provide insights into the mechanistic underpinnings of this skeletal editing protocol.

Palladium/Xu‐Phos Catalyzed Enantioselective Intramolecular Heck Reaction of Unactivated Alkenes

Comprehensive SummaryA highly enantioselective palladium‐catalyzed intramolecular Heck reaction of unactivated alkenes is developed, which provides a powerful route to access a broad range of chiral 3,3‐disubstituted‐2,3‐dihydrobenzofurans bearing all‐carbon quaternary stereocenter of interest in pharmaceutical research. Its salient features include high yield, excellent chemo‐ and enantioselectivity, mild conditions, a broad substrate scope as well as versatile transformations of the product.

Stable Diamine Functionalized Graphene Supported Pd Nanoparticles Showing Excellent Catalytic Activity For Mizoroki–Heck Coupling Reactions

AbstractWe used a simple technique to create palladium nanoparticles on diamine functionalised graphene (Pd(0)‐AAPTMS@G) with an average particle size of 5.5 nm. Our earlier research described the Pd(0)‐AAPTMS@G material as an effective catalyst with outstanding conversion and yields for the Suzuki coupling reaction. We reported the characterisation data for Pd(0)‐AAPTMS@G catalysts previously. Here, we provide a narrative for the excellent selectivity and high yields (92–100 %) for the Mizoroki–Heck coupling product over the same Pd(0)‐AAPTMS@G catalyst. Six uses of the generated catalyst are possible without any activity loss. We also compared the catalyst characterisation for both fresh and reused catalysts.

Post-synthetic modification of near-infrared absorbing cyclodextrin-encapsulated cyanine dyes for controlling absorption wavelength, stability, and singlet oxygen generation

Abstract In this study, near-infrared absorbing rotaxane-type cyanine dyes exhibit high tolerance to various chemical reactions, which is attributed to the encapsulation effect of their cyclic molecules. As a result, rotaxane dyes can be post-modified on the host α-cyclodextrin or guest cyanine skeleton to adjust their solubility, absorption wavelength, stability, and singlet oxygen generation ability. The guest modification product obtained via the Heck reaction demonstrates a red shift of its absorption wavelength owing to the extended conjugation system. Moreover, the products of host modification through the methylation and benzylation of all cyclodextrin hydroxyl groups not only become lipophilic and show extended absorption, but also exhibit higher photooxidation tolerance, lower singlet oxygen generation rate, and increased singlet oxygen tolerance, indicating their potential applicability as highly durable dyes. Furthermore, the outstanding singlet oxygen tolerance of these dyes enables their use in long-life singlet oxygen generators, in which the total amount of singlet oxygen increases. This work demonstrates that an intrinsically unstable near-infrared cyanine dye can be used as a synthetic intermediate by stabilizing it via α-cyclodextrin encapsulation, allowing the post-modification of various properties of cyanine dyes toward the higher-order near-infrared-absorbing materials with complex functionalities and diverse utilities.

Pd Nanocatalysts supported on hollow carbon spheres for heck reaction: Void-confinement effect with varying space size in liquid-phase processes

Pd Nanocatalysts supported on hollow carbon spheres for heck reaction: Void-confinement effect with varying space size in liquid-phase processes

Synthesis of a Family of Pd(II) Complexes Using Pyridyl-Ketone Ligands: Crystal Structure, Thermal, Physicochemical, XRD/HSA, Docking, and Heck Reaction Application.

Four Pd(II) complexes, (dpk)PdCl2 (complex-1), and (dpk)Pd(OAc)2 (complex-2) have been prepared using di(2-pyridyl) ketone as the chelate ligand (dpk). The (dpk·EtOH)PdCl2 (complex-3) and (dpk·EtOH)Pd(OAc)2 (complex-4) were synthesized by selectively introducing complex-1 and complex-2 to an EtOH in situ nucleophilic addition reaction on the O=C of the dpk ligand, respectively. All complexes were characterized using CHN-EA, UV-vis, FT-IR, FAB-MS, EDX, TGA, and NMR physicochemical tools. The XRD-crystallography technique was employed to ascertain the structure of complex-3. The analysis revealed a monoclinic/P21/c crystal system characterized by a square planar structure oriented in the cis direction around the Pd center. Several C-H···Cl and O-H···O H-bonds constructing 2D-S12 and S7 synthons were confirmed via XRD/HSA interactions. The influence of EtOH addition to the O=C group of dpk in (dpk)PdCl2 was documented by using UV-vis/FT-IR spectra and TGA analysis. As catalysts, all complexes have demonstrated a notable catalytic function in the Heck reaction, resulting in a high yield under gentle conditions using iodobenzene and methyl acrylate as model reactions. Moreover, the complex-1 and complex-3 docking activity was evaluated against 1BNA-DNA.

Na2SO3-Promoted Heck Coupling and Homo-Coupling of Arylhydrazines at Room Temperature

Na2SO3-Promoted Heck Coupling and Homo-Coupling of Arylhydrazines at Room Temperature

Stereoselective Synthesis of C-Aryl Glycosides via Palladium-Catalyzed Heck Coupling

Stereoselective Synthesis of C-Aryl Glycosides via Palladium-Catalyzed Heck Coupling

Polymer containing Pd(II) chelates grafted from SBA-15 for C–C bond formation via the Mizoroki–Heck reaction

Polymer containing Pd(II) chelates grafted from SBA-15 for C–C bond formation via the Mizoroki–Heck reaction