Heck Reaction Research Articles

Pd Nanoparticle Supported on N‐Doped Carbon Derived from Sodium Alginate/Melamine Blends as Efficient Heterogeneous Catalyst for Heck Reactions

AbstractN‐doped porous carbon shows great potential in the field of heterogenous supports due to its high porosity, large surface area, rich active sites, and strong chelation with catalytic active metals species. Herein, we successfully prepared a novel N‐doped porous carbon derived from sodium alginate/melamine blends (SAMNC) with different mass ratio through a simple carbonization and activation process. Hierarchical porous structure of the derived N‐doped carbon has been confirmed with the SEM, TEM, and N2 adsorption characterization. After Na2PdCl4 solution impregnation and further reduction process, Pd0 nanoparticles have been uniformly immobilized on the SAMNC support to produce novel Pd@SAMNC catalyst. The optimal Pd@SAMNC‐0.6 possesses a high N content (5.13%), Pd content (5.90%), large BET specific surface area of 1884.5 m2·g−1. Positron annihilation lifetime spectroscopy (PALS) investigation of the porous carbon materials provided the sub‐nano level microporous information proofs of Pd@SAMNC‐0.6 had the capability to provide more active sites for reactions than commercial Pd supported on activated carbon (Pd@AC). Pd@SAMNC‐0.6 catalyst showed superior catalytic efficiency in Heck coupling reaction between aromatic halides and alkenes and can be recycled for 17 runs without significant decrease in catalytic efficiency.

Regioselective Synthesis of α-Vinyl Boronates via a Pd-Catalyzed Mizoroki-Heck Reaction.

We report a palladium-catalyzed synthesis of α-vinyl boronates via a regioselective Mizoroki-Heck reaction between aryl triflates and vinyl boronates. This selectivity is achieved by the use of a 1,5-diaza-3,7-diphosphacyclooctane (P2N2) ligand, which results in minimal formation of the more commonly observed (linear) β-product. The choice of base, solvent, and presence of water are shown to be critical for controlling this outcome, with organic bases, nonpolar solvents, and anhydrous conditions favoring the Heck product and suppressing the competitive Suzuki-Miyaura coupling product.

Bio-inspired fabrication of chitosan/PEO/Ti3C2Tx 2D MXene nanosheets supported palladium composite nanofiber catalysts via electrospinning

In this study, novel chitosan/polyethylene oxide/Ti3C2Tx 2D MXene nanosheets (CS/PEO/Ti3C2Tx) nanofibers were successfully prepared by a continuous electrospinning process. During the electrospinning process, induced by the syringe tip capillary effects and electric field force, the Ti3C2Tx nanosheets were aligned along the direction of the nanofiber formation to occur a highly oriented structure. This well-ordered arrangement of the inorganic Ti3C2Tx nanosheets within the organic polymer matrix nanofiber was similar with nacre-like ‘brick-and-motar’ structure to some extent, resulting in a marked increase in thermal stability and mechanical properties of the resultant CS/PEO/Ti3C2Tx nanofiber. As 4 wt% of Ti3C2Tx nanosheets loaded, the highest tensile strength of the CS/PEO/Ti3C2Tx nanofiber mats was achieved as 31.7 MPa, about two times that of neat CS/PEO nanofibers. Uniformly dispersed Pd nanoparticles in size of about 1.6 nm have been successfully immobilized on the composite nanofiber with a solution impregnation process. With a loading as low as 0.2 mol% of Pd, the resultant Pd@CS/PEO/Ti3C2Tx composite nanofiber catalysts were highly active for both Heck and Sonogashira coupling reactions with broad reactants application scope, and could be recycled 15 runs without significant loss of activities.

Recent Advance in the Reductive Heck Cyclization for the Formation of Five to Nine Member Rings

Abstract: Palladium-catalyzed reactions are widely used for creating carbon-carbon and carbon-heteroatom bonds, with the Heck reaction being particularly valuable for forming rings of various sizes, including mediumsized rings. Recent reports have shown the synthetic potential of intramolecular Heck reactions for assembling rings of seven or more members. While the regioselectivity of this cyclization is often unpredictable in the absence of directing groups, the reductive Heck cyclization strategy can help minimize this issue. Nickel catalysts are also valuable due to their abundance and environmentally friendly nature, playing a pivotal role in producing biologically significant carbocycles and heterocycles. The use of both Pd(0) and Ni(0) catalysts, with or without chiral ligands, has been successful in forming five to nine-member ring heterocycles and carbocycles in a simple, cost-effective manner. This review provides a comprehensive survey of the literature from the past decade on the use of reductive Heck cyclization methodology, including mechanistic details as needed.

Redox-Paired Reductive Heck Reaction and Oxidative Esterification Catalyzed by Mesoionic Carbenes.

Paring a reductive reaction and an oxidative reaction in one reaction could be immensely important in achieving atom economic and environmental advantages. Herein, we report a simple protocol that combines two such reductive Heck reactions and oxidative esterification by using mesoionic carbenes as catalysts to synthesize multiple valuable products under mild conditions.

Palladium‐Catalyzed Bicyclization of 1‐(2,2‐Dibromovinyl)‐2‐Alkenylbenzene with Allenyl Malonates

AbstractPalladium‐catalyzed bicyclization of 1‐(2,2‐dibromovinyl)‐2‐alkenylbenzene with allenyl malonates has been achieved to afford a series of bicyclic compounds. The protocol involves intermolecular carbopalladation of allenes/cyclization/internal Heck reaction. Three C−C bonds and two rings are formed in one step.

A novel Ti³⁺-mediated approach for supporting palladium on anodic TiO2 nanotubes: Toward efficient and recyclable catalysis in the heck reaction

A simple electrochemical reduction technique was employed to generate Ti3+ with strong reducing property on the anodic TiO2 nanotubes (ATNTs). Utilizing Ti3+ as the reducing agent, Pd2+ was successfully reduced in situ to Pd0 on the anodic TiO2 nanotubes (Pd@ATNTs). Various characterization methods were employed to confirm that the proportion of Ti3+ and the size of Pd nanoparticles could be controlled by adjusting the electrochemical reduction voltage. The obtained Pd@ATNTs-2.5 exhibited satisfactory catalytic efficiency (TOF: 1302 h−1) in the Heck reaction between various aryl halides and olefins. Furthermore, Pd@ATNTs-2.5 demonstrated high stability, with no significant loss of catalytic activity observed even after six cycles.

N, N’-bidentate ligand anchored palladium catalysts on MOFs for efficient Heck reaction

Metal-organic frameworks (MOFs), recognized as advanced catalyst carriers due to their adjustable porous, diverse structure and highly exposed active sites, have earned increasing attention for their potential to address the longevity of catalytic centers. In this manuscript, we have devised and synthesized a multifunctional amino-pyridine benzoic acid (APBA) ligand to replace the modulator ligand of the MOF-808 and disperse the palladium catalytic centers atomically on the MOF-APBA. The resulting single-site catalytic system, Pd@MOF-APBA, demonstrates preeminent efficiency and stability, as evidenced by a high average turnover number (95000) and a low metal residue (4.8 ppm) in the Heck reaction. This catalyst has exhibited recyclability for multiple runs without significant loss of reactivity for gram-scale reactions. The catalyst’s high activity and efficiency can be attributed to the suitable electrical properties and structures of the N, N’-bidentate ligand for the catalytic palladium ions, postponing their deactivations, including leaching and agglomeration.

Some Terminally Alkenyl-substituted Porphyrins: Synthesis and Attempts of Heck Reaction Leading to Porphyrin–Azulene Dyads

: The synthesis of meso-tetraphenylporphyrin derivatives, double functionalized in one of the phenyl rings (with a nitro group and carbon substituents), is described. 5-(4- Nitroaryl)-10,15,20-triarylporphyrinates react, in the presence of a base (t-BuOK), with carbanions containing a leaving group at the carbanionic center to give products of substitution of hydrogen at ortho-position to the nitro group via vicarious nucleophilic substitution scheme. Their alkylation with allyl bromide or 4-bromobut-1-en (t-BuOK/DMF, at 0-5°C) leads to porphyrins bearing side alkyl chain with a terminal double bond in yields of up to 82%. The above-mentioned double-substituted intermediates are very convenient substrates for Heck cross-coupling reaction. In this study, the synthesis of porphyrin–azulene dyads is reported. In some cases, the formation of highly conjugated systems is observed, with moderate yield. Their structures are interesting from both the porphyrin and azulene point of view.

Mild and Stereoselective Synthesis of (1E,3E)-Dienes through Silver(I)-Catalyzed β-Hydride Migration from Allylic α-Diazo Esters

AbstractA mild procedure for the diastereoselective preparation of functionalized 1,3-dienes and their synthetic versatility are described herein. The silver-catalyzed decomposition of α-diazo-γ,δ-unsaturated esters through β-hydride migration at room temperature resulted in the stereoselective formation of 12 conjugated (1E,3E)-dienes. Further synthetic post-modifications included intramolecular Heck reaction and hydrogenation, leading to a novel substituted indene and an aliphatic diester, respectively. To rationalize the observed reaction outcome, a computational investigation of the mechanisms was conducted, emphasizing the importance of factors such as metallocarbenoid stability, substituent effects, and microkinetics simulations to better understand the reaction intricacies.

Paired Electrolysis Enables Reductive Heck Coupling of Unactivated (Hetero)Aryl Halides and Alkenes.

The formation of carbon-carbon (C-C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2-Csp3 bonds, the reductive Heck reaction between (hetero)aryl halides and alkenes stands out due to its potential efficiency and broad substrate availability. However, traditional reductive Heck reactions are limited by the use of precious metal catalysts and/or limited aryl halide and alkene compatibility. Here, we present an electrochemically mediated, metal- and catalyst-free reductive Heck reaction that tolerates both unactivated (hetero)aryl halides and diverse alkenes such as vinyl boronates and silanes. Detailed electrochemical and deuterium-labeling studies support that this transformation likely proceeds through a paired electrolysis pathway, in which acid generated by the oxidation of N,N-diisopropylethylamine (DIPEA) at the anode intercepts an alkyl carbanion formed after radical-polar crossover at the cathode. As such, this approach offers a sustainable method for the construction of Csp2-Csp3 bonds from (hetero)aryl halides and alkenes, paving the way for the development of other electrochemically mediated olefin difunctionalization reactions.

Paired Electrolysis Enables Reductive Heck Coupling of Unactivated (Hetero)Aryl Halides and Alkenes

AbstractThe formation of carbon‐carbon (C−C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2−Csp3 bonds, the reductive Heck reaction between (hetero)aryl halides and alkenes stands out due to its potential efficiency and broad substrate availability. However, traditional reductive Heck reactions are limited by the use of precious metal catalysts and/or limited aryl halide and alkene compatibility. Here, we present an electrochemically mediated, metal‐ and catalyst‐free reductive Heck reaction that tolerates both unactivated (hetero)aryl halides and diverse alkenes such as vinyl boronates and silanes. Detailed electrochemical and deuterium‐labeling studies support that this transformation likely proceeds through a paired electrolysis pathway, in which acid generated by the oxidation of N,N‐diisopropylethylamine (DIPEA) at the anode intercepts an alkyl carbanion formed after radical‐polar crossover at the cathode. As such, this approach offers a sustainable method for the construction of Csp2−Csp3 bonds from (hetero)aryl halides and alkenes, paving the way for the development of other electrochemically mediated olefin difunctionalization reactions.

(Invited) Introducing Selectivity into Electrochemical Reactions: From Solution to Surfaces

Induction of asymmetry into electrosynthetic reactions has taken off in recent years for the electrochemical community. As of late most transformations have focused on either simple electrochemical oxidations or reductions, such as the reduction of various ketones to chiral alcohol feedstock molecules, or transition metal cross coupling reactions. At the same time, there has been little effort to introduce asymmetry into cyclization reactions that capitalize on highly reactive radical ion intermediates to accomplish umpolung-type transformations or to fully take advantage of electrode surfaces for manipulating the selectivity of synthetically more complex transformations like transition metal cross coupling reactions. In the case more complex electrochemical transformations, many of the reactions studied have led to either high ee and low yield or low ee and high yield. With this in mind, we are looking new approaches for introducing selectivity into electrochemical transformations by taking advantage of high yielding cathodic cyclization reactions and the Heck reaction. The influence of chiral electrolytes, chiral catalysts and mediators, and modified electrode surfaces on these transformations is being explored with a particular emphasis on both the induction of asymmetry into the reactions and the use of remote functionality in the molecules as a control element. This presentation to be given will detail our progress in these areas.

Total Synthesis of (15R)- and (15S)-Prostaglandin A2.

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5-dimethoxy-tetrahydrofuran employing an organocatalytic domino-aldol reaction, a Mizoroki-Heck reaction, a Wittig reaction as well as an oxidation-decarboxylation sequence. The (15R)-epimer significantly reduced GABA-induced currents through GABAA receptors while its (15S)-epimer did not show any significant effect. These data suggest that (15R)-PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators.

A novel tetra(4-pyridyl)porphyrin-palladium(0) functionalized polyacrylonitrile fiber as highly efficient and recyclable heterogeneous catalyst for the Heck reaction

A novel tetra(4-pyridyl)porphyrin-chelated palladium(0) nanoparticles functionalized polyacrylonitrile fiber (PANTPPF-Pd(0)) was prepared for the first time. Some necessary methods including Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), etc. were used to verify the micro structure and properties of PANTPPF-Pd(0). Furthermore, with the Heck reaction chosen as a model reaction to determine the catalytic activity of PANTPPF-Pd(0), the experiment results shows that PANTPPF-Pd(0) can efficiently catalyze the Heck reaction with high yields (47–99%) in extensive substrate scope (46 examples) under non-solvent condition. Noteworthily, the average size of Pd(0) nanoparticles observed by transmission electron microscopy (TEM) slightly increased from 2.32 nm to 2.59 nm after recycled 8 times achieving an 99% isolated yield of Heck reaction catalyzed by PANTPPF-Pd(0), which proves that the PANTPPF-Pd(0) can maintain satisfactory recyclability. Finally, based on the π-π stacking interactions and dipolar-dipolar interaction between tetra(4-pyridyl)porphyrin moieties in PANTPPF-Pd(0) and substrates, a novel heterogeneous “capture-catalyze” mechanisms was proposed.

A new route to the crinane skeleton via the low-valent titanium-mediated double reduction of cyclic sulfonamides

The construction of a benzo-fused tetracyclic sulfonamide, followed by its low-valent titanium-based reduction and subsequent conversion to racemic crinane is reported. The synthesis of the tetracyclic sulfonamide features a sulfonyl templated, regio- and diastereoselective intramolecular Heck reaction, which installs an all-carbon quaternary centre. Thereafter, a low-valent titanium reduction removes the sulfonyl group, liberating a 3-aryloctahydroindole. A Pictet-Spengler reaction then generates the targeted ethano-bridged phenanthridine core structure of the crinan alkaloids.

Visible light excitation on CuPd/TiN with enhanced chemisorption for catalyzing heck reaction

In this work, we developed plasmonic photocatalyst composed of CuPd alloy nanoparticles supported on TiN, the optimized Cu3Pd2/TiN catalyst shows excellent conversion (>96 %) and selectivity (>99 %) for Heck reaction at 50 °C under visible light irradiation. By in-situ spectroscopic investigations, we find that visible light excitation could achieve stable metallic Cu species on the surface of CuPd alloy nanoparticles, thereby eliminating the inevitable surface oxides of Cu based catalyst. The in-situ formed metallic Cu species under irradiation take advantage of the strong interactions of Cu with visible light, and manifest in the localized surface plasmon resonances (LSPR) photoexcitation. Visible light excitation could further promote the charge transfer between catalytic Pd component and the support TiN, resulting in electron-rich Pd sites on CuPd/TiN. Moreover, light excitation on CuPd/TiN generates strong chemisorption of iodobenzene and styrene, favoring the activation of reactants for Heck reaction. DFT calculations suggest that electron-rich CuPd sites ideally lower the activation energy barrier for the coupling reaction. This work provides valuable insights for mechanistic understanding of plasmonic photocatalysis.

Stereoselective Synthesis of Key Skeleton of Mohangic Acids A‐E

AbstractThe key skeleton that could allow to access structurally intriguing mohangic acids A−E has been synthesized in stereoselective manner. The salient features of this synthesis include Evans syn‐aldol reaction to construct the C‐11 and C‐12 centers, HWE olefination to construct C14−C15 bond, Evans asymmetric methylation to install C‐14 center and Crimmins acetate aldol to generate C‐15 center whereas Wittig and Takai olefinations to prepare the C8–C9 & C6–C7 alkenes, respectively, and Heck reaction to couple C1–C5 & C6–C17 segments of the molecules. The developed route is highly modular and useful for accessing diverse natural product like molecules for future investigations.

Key Blocks for Constructing π-Conjugated Systems Based on Thieno[3,2-b]pyrroles

Cross-coupling products with isobutyl acrylate were obtained by the Heck reaction based on dibromides of methyl esters of 4-methyl- and 4-benzyl-4H-thieno[3,2-b]pyrrole-5-carboxylic acids.

Role of Ionic Liquids as Solvent & Catalyst for Heck and Suzuki Reactions: A Comprehensive Review

Role of Ionic Liquids as Solvent & Catalyst for Heck and Suzuki Reactions: A Comprehensive Review