Diels-Alder Research Articles

Self-Healing and Recyclable Polyurethane/Nanocellulose Elastomer Based on the Diels–Alder Reaction

With the background of the fossil fuel energy crisis, the development of self-healing and recyclable polymer materials has become a research hotspot. In this work, a kind of cross-linking agent with pendent furan groups was first prepared and then used to produce the Polyurethane elastomer based on Diels–Alder chemistry (EPU–DA). In addition, in order to further enhance the mechanical properties of the elastomer, cellulose nanofibers (CNFs) were added into the Polyurethane system to prepare a series of composites with various contents of CNF (wt% = 0.1~0.7). Herein, the FTIR and DSC were used to confirm structure and thermal reversible character. The tensile test also indicated that the addition of CNF increased the mechanical properties compared to the pure Polyurethane elastomer. Due to their reversible DA covalent bonds, the elastomer and composites were recycled under high-temperature conditions, which extends Polyurethane elastomers’ practical applications. Moreover, damaged coating can also be repaired, endowing this Polyurethane material with good potential for application in the field of metal protection.

Chiral Supramolecular Self-Assembly Catalysts with Enhanced Metal Ion Interaction for Higher Enantioselectivity.

Understanding the interaction between metal ions as catalytic centers and supramolecular scaffolds as chiral substrates plays an important role in developing chiral supramolecular catalysts with high enantioselectivity. Herein, we found that compared with l-norleucine chiral amphiphile (l-NorC16), l-methionine chiral amphiphile (l-MetC16) with the only heteroatom of S site difference in the hydrophilic group can form a similar supramolecular chiral nanoribbon (NR) with the bilayer structure through the self-assembly approach; yet, the interaction between the Cu(II) ion catalytic centers and supramolecular scaffolds is reinforced, favoring the chirality transfer and therefore enhancing their catalytic enantioselectivity of Diels-Alder reaction from 23% [l-NorC16-NR-Cu(II)] to 78% [l-MetC16-NR-Cu(II)]. Our work demonstrates a new strategy from the perspective of strengthening the metal ion-supramolecular scaffold interaction for the preparation of chiral supramolecular catalysts with good catalytic enantioselectivity.

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially,N-Boc pyrroles and alkynes are converted intoN-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Hunting for the Intermolecular Diels-Alderase.

ConspectusThe Diels-Alder reaction is well known as a concerted [4 + 2] cycloaddition governed by the Woodward-Hoffmann rules. Since Prof. Otto Diels and his student Kurt Alder initially reported the intermolecular [4 + 2] cycloaddition between cyclopentadiene and quinone in 1928, it has been recognized as one of the most powerful chemical transformations to build C-C bonds and construct cyclic structures. This named reaction has been widely used in synthesizing natural products and drug molecules. Driven by the synthetic importance of the Diels-Alder reaction, identifying the enzyme that stereoselectively catalyzes the Diels-Alder reaction has become an intriguing research area in natural product biosynthesis and biocatalysis. With significant progress in sequencing and bioinformatics, dozens of Diels-Alderases have been characterized in microbial natural product biosynthesis. However, few are evolutionally dedicated to catalyzing an intermolecular Diels-Alder reaction with a concerted mechanism.This Account summarizes our endeavors to hunt for the naturally occurring intermolecular Diels-Alderase from plants. Our research journey started from the biomimetic syntheses of D-A-type terpenoids and flavonoids, showing that plants use both nonenzymatic and enzymatic intermolecular [4 + 2] cycloadditions to create complex molecules. Inspired by the biomimetic syntheses, we identify an intermolecular Diels-Alderase hidden in the biosynthetic pathway of mulberry Diels-Alder-type cycloadducts using a biosynthetic intermediate probe-based target identification strategy. This enzyme, MaDA, is an endo-selective Diels-Alderase and is then functionally characterized as a standalone intermolecular Diels-Alderase with a concerted but asynchronous mechanism. We also discover the exo-selective intermolecular Diels-Alderases in Morus plants. Both the endo- and exo-selective Diels-Alderases feature a broad substrate scope, but their mechanisms for controlling the endo/exo pathway are different. These unique intermolecular Diels-Alderases phylogenetically form a subgroup of FAD-dependent enzymes that can be found only in moraceous plants, explaining why this type of [4 + 2] cycloadduct is unique to moraceous plants. Further studies of the evolutionary mechanism reveal that an FAD-dependent oxidocyclase could acquire the Diels-Alderase activity via four critical amino acid mutations and then gradually lose its original oxidative activity to become a standalone Diels-Alderase during the natural evolution. Based on these insights, we designed new Diels-Alderases and achieved the diversity-oriented chemoenzymatic synthesis of D-A products using either naturally occurring or engineered Diels-Alderases.Overall, this Account describes our decade-long efforts to discover the intermolecular Diels-Alderases in Morus plants, particularly highlighting the importance of biomimetic synthesis and chemical proteomics in discovering new intermolecular Diels-Alderases from plants. Meanwhile, this Account also covers the evolutionary and catalytic mechanism study of intermolecular Diels-Alderases that may provide new insights into how to discover and design new Diels-Alderases as powerful biocatalysts for organic synthesis.

Large Molecular Rotation in Crystal Changes the Course of a Topochemical Diels-Alder Reaction from a Predicted Polymerization to an Unexpected Intramolecular Cyclization.

A designed anthracene-based monomer for topochemical Diels-Alder cycloaddition polymerization crystallized with head-to-tail arrangement of molecules, as revealed by single-crystal X-ray diffraction (SCXRD) analysis. The diene and dienophile units of adjacent monomer molecules are aligned at an average distance of 4.6 Å, suggesting a favorable crystalline arrangement for their intermolecular Diels-Alder cycloaddition reaction to form a linear polymer . Surprisingly, heating the monomer crystals at a temperature above 125 °C resulted in the formation of intramolecular Diels-Alder cycloadduct, which could be characterized by various spectroscopy and SCXRD analysis. Various time-dependent studies such as NMR, PXRD, and DSC, studies established that the reaction followed topochemical pathway. Schmidt's topochemical postulates are generally used to predict the topochemical reactivity and product, by analyzing the crystal structure of the reactant. Though the crystal arrangement predicted polymerization, upon heating the molecule avoided this pathway by undergoing a large rotation to form an intramolecular cycloadduct.Theoretical calculations supported the feasibility of the rotation, exploiting the flexibility of the molecule and voids present. These findings caution that the reliance on Schmidt's criteria for topochemical reactions may sometimes be misleading, especially in heat-induced reactions.

Asymmetric Synthesis of (-)-Cannabidiol (CBD), (-)-Δ9-Tetrahydrocannabinol (Δ9-THC) and Their cis Analogs Using an Enantioselective Organocatalyzed Diels-Alder Reaction.

Herein we describe an asymmetric synthesis of the pharmacologically relevant natural (-)-trans-CBD and psychoactive (-)-trans-Δ9-THC, as well as their synthetic cis diastereomers. The key step is an enantioselective Diels-Alder reaction catalyzed by a prolinol-based catalyst, which provides the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimization of the substituted resorcinol protecting groups to avoid harsh and low-yield deprotection of the acid sensitive resorcinol moiety is also described.

Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis

To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins. Through iron atom substitution by Lewis acidic gallium (Ga) iron and computational calculations, we confirm that the ubiquitous Fe-S cluster efficiently functions as Lewis acid to accelerate the tandem [4+2] cycloaddition and Michael addition reactions by lowering free energy barriers. Our work highlights Nature’s ingenious strategy to generate complex molecule structures using the ubiquitous Fe-S protein. Furthermore, our study sheds light on the future design of Fd as a versatile Lewis acid catalyst for [4+2] cycloaddition reactions.

Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis

To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins. Through iron atom substitution by Lewis acidic gallium (Ga) iron and computational calculations, we confirm that the ubiquitous Fe-S cluster efficiently functions as Lewis acid to accelerate the tandem [4+2] cycloaddition and Michael addition reactions by lowering free energy barriers. Our work highlights Nature’s ingenious strategy to generate complex molecule structures using the ubiquitous Fe-S protein. Furthermore, our study sheds light on the future design of Fd as a versatile Lewis acid catalyst for [4+2] cycloaddition reactions.

Synthesis of High Mechanical Strength and Thermally Recyclable and Reversible Polyurethane Adhesive by Diels–Alder Reaction

AbstractRecyclability of polyurethane materials is significant to relieve environmental problems caused by damaged polymers. Inspired by plenty of self‐healing properties based on dynamic covalent bonds. A high mechanical strength and thermally reversible polyurethane adhesive are acquired through co‐polymerization of poly‐1,4‐butylene adipate glycol (PBA), soybean oil‐based polyol (MESO), and toluene diisocyanate (TDI) whose linear polymer chains are constructed by Diels–Alder reaction between furfuryl alcohol (FA) and bismaleimide (BMI), named DAPU. Further, the obtained polyurethane adhesives show great recyclability, mechanical performance (Whose tensile strength can reach 91.7 MPa), and appropriate self‐healing ability through the thermally reversible Diels–Alder covalent bonds and hydrogen bonds between urethane groups, which may pave a way for further development of recyclable materials.

Synthesis of High Mechanical Strength and Thermally Recyclable and Reversible Polyurethane Adhesive by Diels–Alder Reaction

AbstractRecyclability of polyurethane materials is significant to relieve environmental problems caused by damaged polymers. Inspired by plenty of self‐healing properties based on dynamic covalent bonds. A high mechanical strength and thermally reversible polyurethane adhesive are acquired through co‐polymerization of poly‐1,4‐butylene adipate glycol (PBA), soybean oil‐based polyol (MESO), and toluene diisocyanate (TDI) whose linear polymer chains are constructed by Diels–Alder reaction between furfuryl alcohol (FA) and bismaleimide (BMI), named DAPU. Further, the obtained polyurethane adhesives show great recyclability, mechanical performance (Whose tensile strength can reach 91.7 MPa), and appropriate self‐healing ability through the thermally reversible Diels–Alder covalent bonds and hydrogen bonds between urethane groups, which may pave a way for further development of recyclable materials.

Introducing Diels‐Alder reaction with carbon nanotubes for the enhanced repair performance of epoxy resin modified asphalt

AbstractEpoxy asphalt, a thermosetting polymer, is characterized by stable, irreversible internal chemical bonds that prevent recovery and spontaneous micro‐crack healing, unlike conventional asphalt. This study introduces a renewable nano‐modifier synthesized via esterification of carboxyl‐functionalized carbon nanotubes (CNTs‐COOH) and furfuryl alcohol (FA), termed CNTs‐FA. The successful synthesis of CNTs‐FA was confirmed through various microscopic techniques. Integrating CNTs‐FA into epoxy asphalt materials, the optimal dosage was identified as 0.05% of the total epoxy asphalt mass using tensile tests and fluorescence microscopy. Thermal reversible effects and mechanisms were further analyzed through multiple regeneration cycles using tensile properties, fluorescence microscopy, and infrared spectroscopy. The study elucidates that the thermal reversibility in epoxy asphalt is facilitated by the Diels‐Alder (DA) reaction between the conjugated diene structure in FA and the curing agent oleylamine. This research provides an effective solution to the non‐recoverability and unrepairable micro‐cracks of traditional epoxy asphalt mixtures.Highlights CNTs‐FA was successfully prepared by esterification reaction. Using nano modification methods, introduce DA reaction into curing system. Renewable function of epoxy asphalt by DA reversible reaction.

Introducing Diels‐Alder reaction with carbon nanotubes for the enhanced repair performance of epoxy resin modified asphalt

AbstractEpoxy asphalt, a thermosetting polymer, is characterized by stable, irreversible internal chemical bonds that prevent recovery and spontaneous micro‐crack healing, unlike conventional asphalt. This study introduces a renewable nano‐modifier synthesized via esterification of carboxyl‐functionalized carbon nanotubes (CNTs‐COOH) and furfuryl alcohol (FA), termed CNTs‐FA. The successful synthesis of CNTs‐FA was confirmed through various microscopic techniques. Integrating CNTs‐FA into epoxy asphalt materials, the optimal dosage was identified as 0.05% of the total epoxy asphalt mass using tensile tests and fluorescence microscopy. Thermal reversible effects and mechanisms were further analyzed through multiple regeneration cycles using tensile properties, fluorescence microscopy, and infrared spectroscopy. The study elucidates that the thermal reversibility in epoxy asphalt is facilitated by the Diels‐Alder (DA) reaction between the conjugated diene structure in FA and the curing agent oleylamine. This research provides an effective solution to the non‐recoverability and unrepairable micro‐cracks of traditional epoxy asphalt mixtures.Highlights CNTs‐FA was successfully prepared by esterification reaction. Using nano modification methods, introduce DA reaction into curing system. Renewable function of epoxy asphalt by DA reversible reaction.

Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach.

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 μg/mL) against S. aureus compared to platensimycin.

Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach.

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 μg/mL) against S. aureus compared to platensimycin.

Furan and benzene ring formation in cellulose char: the roles of 5-HMF and reducing ends.

The authors previously proposed that 5-hydroxymethylfurfural (5-HMF) can be produced from the reducing ends of cellulose as a key intermediate during carbonization. The present work investigated the mechanisms by which furan and benzene rings are formed in cellulose char based on carbonization at 280 °C using 13C-labeled 5-HMF together with 13C-labeled glucose (as a model for the cellulose reducing ends). Glycerol was added to the 5-HMF to prevent the formation of stable glassy polymers. The resulting char was subjected to pyrolysis gas chromatography/mass spectrometry (764 °C, 5 s hold time) and the incorporation of 13C in furan-, phenol-, benzofuran- and benzene-type fragments was assessed. The apparent formation mechanisms include a direct rearrangement of the six carbons of 5-HMF to phenols, Diels-Alder reactions of furan rings with double bonds to give benzofurans and a more random process involving reactive fragments producing benzene rings. On the basis of these results, the roles of 5-HMF and reducing ends during cellulose carbonization are discussed herein.

Synthesis of Polyoxygenated 4,5-Diarylpyridazines with Antiproliferative and Antitubulin Activity via Inverse Electron-Demand Diels-Alder Reaction of 1,2,4,5- Tetrazine#

Synthesis of Polyoxygenated 4,5-Diarylpyridazines with Antiproliferative and Antitubulin Activity via Inverse Electron-Demand Diels-Alder Reaction of 1,2,4,5- Tetrazine#

Insights into the mechanism, selectivity, and substituent effects in the Diels-Alder reaction of azatrienes with electron-rich dienophiles: An MEDT study

The reactivity and mechanistic intricacies of azatrienes in Diels-Alder reactions have been relatively unexplored despite their intriguing potential applications. In this study, we employ Molecular Electron Density Theory to theoretically investigate the hetero-Diels–Alder reaction involving azatrienes with ethyl vinyl ether and allenyl methyl ether. Analysis of Conceptual Density Functional Theory, energetic profiles, and the topological characteristics is conducted to elucidate the reactions. The revealed mechanism manifests as a polar one-step two-stages process under kinetic control. We establish a clear relationship of between the periselectivity, regioselectivity, and stereoselectivity on one hand and the characteristics of the reactions mechanism on the other hand. The influence of weak interactions on reaction activation barriers and bonding evolution are discussed in detail. We demonstrate that substituents enhancing the reverse electron density flux facilitate the feasibility of the reactions. The results lay ground for a meticulous control of the reaction of azatriene in similar synthetic scenarios.

Catalytic co-pyrolysis of poplar tree and polystyrene with HZSM-5 and Fe/HZSM-5 for production of light aromatic hydrocarbons

The catalytic co-pyrolysis of biomass and plastic waste is a highly effective approach for the production of light aromatic hydrocarbons. In this study, catalytic co-pyrolysis experiments were conducted on poplar tree (PT) and polystyrene (PS) using pyrolyzer coupled with gas chromatography/mass spectrometry (Py-GC/MS). The experiments were carried out at a temperature of 550 °C and a mixing ratio of 1:1. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) techniques were employed for the characterization of HZSM-5 and Fe/HZSM-5 catalysts. The findings indicated that the metallic Fe in the HZSM-5 catalyst led to an enhanced production of monocyclic aromatic hydrocarbons (MAH) during the catalytic co-pyrolysis of PT and PS. The proportion of MAH in the products obtained from HZSM-5 and Fe/HZSM-5 catalyst was determined to be 85.84% and 90.87%, respectively. In the catalytic co-pyrolysis of biomass and plastic waste, several crucial reactions took place, including deoxidation, olefins aromatization, and Diels-Alder reaction between furans and olefins. In the presence of Fe metal, the HZSM-5 catalyst exhibited enhanced selectivity towards valuable MAH while effectively suppressing the formation of polycyclic aromatic hydrocarbons, resulting in an increase in MAH production to 90.87%.

Anticancer activity of synthesized 5-benzyl juglone on selected human cancer cell lines.

Cancer is a malignant disease that causes millions of deaths each year worldwide. As one of the cancer therapeutic strategies, chemotherapy is a means to destroy rapidly dividing cells. The main problem with cancer chemotherapy is the lack of selectivity of conventional chemotherapeutic drugs, leading to toxicity towards normal cells. Therefore, the discovery of anticancer agents with selectivity for fast-growing cancer cells was desirable. In this study, we report the synthesis and identification of the novel 5-benzyl juglone as a potential anticancer agent with selectivity toward certain cancer cell lines. An efficient synthetic method for 5-benzyl juglone has been established. The proliferation of cancer cell lines and a normal cell line treated by the target compound were studied using an MTT assay. In addition, the cell cycle arrest and apoptosis were determined by flow cytometry. Based on the Diels-Alder (D-A) reaction between 3,6-dimethoxy benzyne intermediate with furan, further acid-catalyzed intramolecular rearrangement and CAN-mediated oxidation, a convenient synthesis of 5-benzyl juglone has been achieved with high overall yield. The results from in vitro biological evaluation indicated that the juglone derivative exhibited potent antiproliferative activity against HCT-15 human colorectal cancer cells with an IC50 value of 12.27 μM. It exerted high inhibitory activity toward MCF-7 human breast cancer cells and, to a much lesser extent, to corresponding MCF-10A human breast epithelial normal cells with the IC50 ratio (IC50 in MCF-7 divided by IC50 in MCF-10A) of 0.62. The mechanistic investigations indicated that 5-benzyl juglone could induce cell cycle arrest at the G0/G1 phase and promote apoptosis of HCT-15 cells. The apoptotic effects possibly also contributed to its higher selectivity toward cancer cells than normal cell lines.

Pyrolysis-catalysis of waste tire to enhance the aromatics selectivity via metal-modified ZSM-5 catalysts

Excessive untreated waste tires (WT) have posed threats to the environment and human health. Pyrolysis-catalysis, as a promising treatment technology, could convert WT into high-valued products such as pyrolysis oil. Moreover, BTX compounds (Benzene, toluene, and xylene) were important raw materials in the chemical industry. In order to sharply increase the BTX selectivity in the pyrolytic oil, transition metals (Ni and Fe) were impregnated on the ZSM-5 catalyst. Furthermore, this paper also explored the effect of catalysis modes, catalysts-to-feedstock mass ratios, and catalysis temperatures on the distribution of the aromatics in the WT pyrolysis-catalysis oil. The results suggested that the optimal operating parameters for BTX compound production with a selectivity of 39.87% were in-situ mode, catalysis temperature=600 °C, and catalyst-to-feedstock mass ratio=1:1 by applying Ni/ZSM-5. According to the GC-MS identification results, it proposed that the Diels-Alder reaction of isoprene and cracking and recombination of limonene in the aliphatic hydrocarbon pool were the main paths to generate the aromatics, while the addition of ethylene radicals in the monocyclic aromatic hydrocarbon (MAH) and polycyclic aromatic hydrocarbon (PAH) pools was dominant in the growth of the aromatics. The study provided a viable approach for upgrading WT to produce high-value aromatic products.