Search

AbstractCoating of magnetic nanoparticles with functional polymers increases the applicability of these nanomaterials. A modular approach to functionalizing these polymer coatings can be achieved using click chemistry. This work reports the synthesis of magnetic nanoparticles coated with a dopamine anchoring group containing polymer with furan groups as side chain residues. Using the ‘graft-to’ approach, polymers are coated onto magnetic nanoparticles using a simple place exchange reaction. Various analytical techniques were used to characterize the polymer-coated nanoparticles for their size and surface composition. Utilization of poly(ethylene glycol) (PEG)-based polymer renders the magnetic nanoparticles water dispersible. The presence of the furan ring on the polymer brushes enables their facile functionalization using a maleimide group-bearing molecule under catalyst-free conditions. A hydrophobic fluorescent dye, used as a model drug, is conjugated onto the nanoparticles using the Diels-Alder reaction. One can anticipate that the facile fabrication and functionalization of these clickable polymer-coated magnetic nanoparticles will be attractive for various biomedical applications. [ABSTRACT FROM AUTHOR]

2‐Arylsulfonyl‐2‐azabicyclo[2.2.1]hept‐5‐enes, synthesized via the cycloaddition of chloral‐ or dichloro(phenyl)acetaldehyde N‐arylsulfonylimines to cyclopentadiene, undergo Wagner‐Meerwein rearrangement under the action of bromine or chlorine to afford 3‐polychloro‐6,7‐dyhalogenated 2‐arylsulfonylazabicyclo[2.2.1]heptanes. [ABSTRACT FROM AUTHOR]

The role of Lewis and Brønsted acid sites in the Diels‐Alder cycloaddition (DAC) of ethylene to 2,5‐dimethylfuran (2,5‐DMF) to p‐xylene was investigated. Amorphous silica catalysts containing Al3+ (ASA), Ga3+ (ASG), and In3+ (ASI) were prepared via homogeneous deposition‐precipitation. Silica modified with Zr4+ (ASZ) was prepared by impregnation. Their acidic properties were characterized by various IR and NMR spectroscopic techniques. Measurements using pyridine as a probe molecule highlighted the presence of mostly Lewis acid sites (LAS) in all materials. Using CO as a probe, in contrast, demonstrated the existence of Brønsted acid sites (BAS) in ASA and ASG, which were nearly absent in ASI and ASZ. Differences in basic strength can explain the contrast in results observed between the two probe molecules. The highest p‐xylene yield (~20 %) in the DAC reaction, could be achieved with ASA and ASG. The lack of BAS in ASI and ASZ resulted in inferior performance in the DAC, with p‐xylene yields below 5 %. These results indicate the importance of BAS for the DAC reaction. Several other heterogeneous and homogeneous catalysts were explored for the DAC reaction to show the generality of our conclusion that BAS play a critical role in obtaining p‐xylene from 2,5‐DMF and ethylene. [ABSTRACT FROM AUTHOR]

An efficient, concise 5-step synthetic approach to γ-aminobutyric acid (GABA) derivatives bearing bridged bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane rings was developed, which consists of Diels-Alder cycloaddition to construct the bridged bicyclic rings with a nitrile functionality, hydrogenation, LDA-mediated SN2 alkylation to introduce acetate moiety at the α-position of nitrile, reduction of the nitrile functionality to amino group followed by intramolecular formation of lactam and finally acidic hydrolysis of lactam to give the desired GABA derivatives (1 and 19 as HBr salts). The reaction conditions of Diels-Alder cycloaddition and LDA-mediated SN2 alkylation were intensively optimized to improve the yields. The stereochemistry of the SN2 reaction involved in the bicyclo[2.2.1]heptane ring system was unambiguously elucidated by single-crystal X-ray diffraction. This synthetic approach possesses advantages of less reaction steps, high overall yields and avoidance of toxic reagents, and may find wide applications in the synthesis of other GABA derivatives with similar bicyclic or polycyclic rings. [ABSTRACT FROM AUTHOR]

The PyBox–La(OTf)3-catalyzed enantioselective Diels–Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

Metal-organic frameworks (MOFs) have attracted considerable interest as emerging heterogeneous catalysts for organic transformations of synthetic utility. Herein, a Lewis-acidic MOF, {[Cu3(PEIP)2(5-NH2-mBDC)(DMF)]·7DMF}∞, denoted as Cu(ΙΙ)-PEIP, has been synthesized via a one-pot process and deployed as an efficient heterogeneous catalyst for a Diels–Alder cycloaddition. Specifically, the [4 + 2] cycloaddition of 13 substituted azachalcone dienophiles with cyclopentadiene has been investigated. MOF-catalyzed reaction conditions were optimized, leading to the selection of water as the solvent, in the presence of 10% mol sodium dodecyl sulfate (SDS) to address substrate solubility. The Cu(II)-PEIP catalyst showed excellent activity under these green and mild conditions, exhibiting comparable or, in some cases, superior efficiency to a homogeneous catalyst often employed in Diels–Alder reactions, namely, Cu(OTf)2. The nature of the azachalcone substituent played a significant role in the reactivity of the dienophiles, with electron-withdrawing (EW) substituents enhancing conversion and electron-donating (ED) ones exhibiting the opposite effect. Coordinating substituents appeared to enhance the endo selectivity. Importantly, the Cu(II)-PEIP catalyst can be readily isolated from the reaction mixture and recycled up to four times without any significant reduction in conversion or selectivity. [ABSTRACT FROM AUTHOR]

The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels-Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.

Post‐synthetic modification (PSM) is an effective approach for the tailored functionalization of metal‐organic architectures, but its generalizability remains challenging. Herein we report a general covalent PSM strategy to functionalize PdnL2n metal‐organic cages (MOCs, n=2, 12) through an efficient Diels–Alder cycloaddition between peripheral anthracene substituents and various functional motifs bearing a maleimide group. As expected, the solubility of functionalized Pd12L24 in common solvents can be greatly improved. Interestingly, concentration‐dependent circular dichroism and aggregation‐induced emission are achieved with chiral binaphthol (BINOL)‐ and tetraphenylethylene‐modified Pd12L24, respectively. Furthermore, Pd12L24 can be introduced with two different functional groups (e.g. chiral BINOL and achiral pyrene) through a step‐by‐step PSM route to obtain chirality‐induced circularly polarized luminescence. Moreover, similar results are readily observed with a smaller Pd2L4 system. [ABSTRACT FROM AUTHOR]

Making use of a Diels–Alder approach based on various α,β-unsaturated 2-carbomethoxy-4,4-dimethyl-1-tetralones as novel dienophiles, the corresponding polycyclic adducts could be efficiently synthesized in good to high yields (74~99%) in the presence of Lewis acid (e.g., SnCl4). Accordingly, a synthetically useful platform is established to provide a focused aromatic polyketide-like library for screening of potential natural and non-natural antimicrobial agents. [ABSTRACT FROM AUTHOR]

The overexpression of protein phosphatase 5 (PP5) has been correlated to tumor cell reproduction, making it a candidate for small molecule drug therapy. Prior work has focused on functionalized and decorated scaffolds that maximize contacts within and around the active site. The assembly and testing of cantharidin derivatives decorated with functionalized attachments has been our focus in order to affect the optimal binding of PP5. Condensation of 2-hydroxymethylfuran with allyl isocyanate meets the metrics of the rapid installment of functionality, as part of the core scaffold. Once condensed, cycloaddition followed by hydrogenation produces the desired derivative of norcantharidin in three synthetic steps. [ABSTRACT FROM AUTHOR]

The overexpression of protein phosphatase 5 (PP5) has been correlated to tumor cell reproduction, making it a candidate for small molecule drug therapy. Prior work has focused on functionalized and decorated scaffolds that maximize contacts within and around the active site. The assembly and testing of cantharidin derivatives decorated with functionalized attachments has been our focus in order to affect the optimal binding of PP5. Condensation of 2-hydroxymethylfuran with allyl isocyanate meets the metrics of the rapid installment of functionality, as part of the core scaffold. Once condensed, cycloaddition followed by hydrogenation produces the desired derivative of norcantharidin in three synthetic steps.

The formal Diels‐Alder (D−A) reaction of alkenes with 1,2‐diimine and related substrates is designed and studied by density functional theory (DFT), multi‐reference and quasi‐classical trajectory calculations in the presence of a benzoquinone‐based organic oxidant. The reaction is found to occur through an Addition‐Coupled Electron Transfer (ACET) with one electron transferred to the oxidant in one elementary step, affording a carbon‐radical, followed by an intramolecular radical addition. The overall barrier is significantly reduced as compared to the traditional concerted D−A reaction. The reaction with two new bond formation events in one elementary step coupled with electron transfer (concerted Pericyclic‐Coupled Electron Transfer, cPeriCET) was not found. This work reveals that coupling to electron transfer might be a tool to achieve cycloaddition reactions with unactivated substrates. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have attracted considerable interest as emerging heterogeneous catalysts for organic transformations of synthetic utility. Herein, a Lewis-acidic MOF, {[Cu3(PEIP)2(5-NH2-mBDC)(DMF)]·7DMF}∞, denoted as Cu(ΙΙ)-PEIP, has been synthesized via a one-pot process and deployed as an efficient heterogeneous catalyst for a Diels–Alder cycloaddition. Specifically, the [4 + 2] cycloaddition of 13 substituted azachalcone dienophiles with cyclopentadiene has been investigated. MOF-catalyzed reaction conditions were optimized, leading to the selection of water as the solvent, in the presence of 10% mol sodium dodecyl sulfate (SDS) to address substrate solubility. The Cu(II)-PEIP catalyst showed excellent activity under these green and mild conditions, exhibiting comparable or, in some cases, superior efficiency to a homogeneous catalyst often employed in Diels–Alder reactions, namely, Cu(OTf)2. The nature of the azachalcone substituent played a significant role in the reactivity of the dienophiles, with electron-withdrawing (EW) substituents enhancing conversion and electron-donating (ED) ones exhibiting the opposite effect. Coordinating substituents appeared to enhance the endo selectivity. Importantly, the Cu(II)-PEIP catalyst can be readily isolated from the reaction mixture and recycled up to four times without any significant reduction in conversion or selectivity.

The potential of amorphous silica‐alumina (ASA) to substitute zeolites (HBeta‐25) for the synthesis of p‐xylene via Diels‐Alder cycloaddition (DAC) of ethylene to 2,5‐dimethylfuran (2,5‐DMF) is investigated. ASA were prepared via homogeneous deposition‐precipitation of Al on SiO2. ASA shows good yields of p‐xylene (20–25 % after 18 hours) compared to bare silica and γ‐alumina. Brønsted acid sites (BAS) were identified as the active sites for the DAC reaction. The catalytic performance correlated strongly with the BAS concentration. Increasing the acidity of ASA is, however, limited by formation of agglomerated alumina‐type clusters at higher Al3+ content. While HBeta‐25 zeolite shows initially a slightly higher performance in terms of p‐xylene yield, ASA is the better catalyst upon calcination‐regeneration of the used catalyst. These results furthermore confirm that confinement in zeolite micropores is not a prerequisite for the DAC reaction between 2,5‐DMF and ethylene. [ABSTRACT FROM AUTHOR]

[Display omitted] • Trisarcglaboids A and B were new family lindenane sesquiterpenoid trimer. • Compound 1 was highly cytotoxic to five human cancer cell lines. • Compound 1 potentially induced apoptosis by blocking Akt phosphorylation. Trisarcglaboids A and B (1 and 2), representing the first example of lindenane sesquiterpenoid trimers repolymerized based on the classical [4 + 2] type dimer, together with known biogenic precursors chlorahololide D (3) and sarcandrolide A (4), were identified as chemical components of the root of Sarcandra glabra. The novel trimeric lindenane sesquiterpenoid skeletons, including their absolute configurations, were characterized using MS, NMR, ECD, and X-ray single crystal diffraction. The proposed Diels-Alder cycloaddition between Δ 2(3) of the tiglic acyl group of the classical [4 + 2] type dimer and Δ 15(4),5(6) of the third lindenane may serve as the key biogenic step. In addition, compound 1 exerted significant cytotoxicity against five human cancer cell lines with IC 50 values ranging from 1 to 7 μM, potentially through blocking Akt phosphorylation and activating the endogenous apoptosis pathway. [ABSTRACT FROM AUTHOR]

Making use of a Diels–Alder approach based on various α,β-unsaturated 2-carbomethoxy-4,4-dimethyl-1-tetralones as novel dienophiles, the corresponding polycyclic adducts could be efficiently synthesized in good to high yields (74~99%) in the presence of Lewis acid (e.g., SnCl4). Accordingly, a synthetically useful platform is established to provide a focused aromatic polyketide-like library for screening of potential natural and non-natural antimicrobial agents.

In the past two decades, quantum chemistry has become an indispensable tool for the reliable interpretation of experimental measurements of a wide range of molecular properties of fullerene and its derivatives. Among the modern quantum‐chemical methods of analysis, preference is given to the density functional theory. This review describes the computational studies that demonstrate rather comprehensively the prospects of quantum‐chemical calculations in many fields of the chemistry of fullerene and its derivatives, such as geometric parameters, stability of structures, molecular spectroscopic properties, electronic structures, the nature of bonds, thermochemistry, and simulation of the kinetics and mechanism of processes. The review focuses on the most typical cycloaddition reactions such as Diels–Alder, Prato and Bingel–Hirsch reactions. The general trends of scientific studies in this area are also discussed and a wide range of references is provided where the readers can find technical details of computational approaches that may be of interest for them. [ABSTRACT FROM AUTHOR]

An approach to hydrocarbazoles bearing an all‐carbon quaternary center at C4a position was developed via a Brønsted acid‐initiated Diels‐Alder cycloaddition/retro‐aza‐Michael addition cascade process from azepino[4,5‐b]indoles and commercially available dienophiles. The method provided a range of hydrocarbazoles in 63–99% yields. The practicality of this transformation was demonstrated by a scale‐up experiment and various transformations to several hydrocarbazole derivatives and the tetracyclic indoline scaffold. Moreover, hetero‐Diels‐Alder cycloadditions of azepino[4,5‐b]indoles were explored with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (PTAD) and 82–99% yields were obtained. [ABSTRACT FROM AUTHOR]

The substituted-9-bromo-9,10-dihydro-9,10-ethanoanthracenes ortho 8a-12a and meta 8b-13b have been synthesized via Diels-Alder reaction under microwave conditions. The cycloadduct isomers ortho 8a-11a and meta 8b-11b, with priority to ortho 8a-11a, were obtained from the reaction of 9-bromoanthracene 1 with acrylonitrile 2, 2-chloroacrylonitrile 3, methacryloyl chloride 4 and acrylic acid 5, while ortho 12a and meta 12b, with priority to meta 12b, was obtained from the reaction of 9-bromoanthracene 1 with 1-cynao vinyl acetate 6. Interestingly, the only isomer meta 13b was obtained from the reaction of 9-bromoanthracene 1 with phenyl vinyl sulfone 7. The results proved that the steric or/and electronic nature of the dienophile substituent is/are playing significant roles in the regioselectivity and isomers ratio.

The PyBox-La(OTf) 3 -catalyzed enantioselective Diels-Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

A new octaphenyl[4.4]triphenylparacyclophanediene was readily synthesized in six steps from p -xylene via the installment of bromine atoms, replacement with a vinyl group, carbonylative coupling, intermolecular followed by intramolecular double Grubbs olefin metathesis, Knoevenagel condensation, and Diels–Alder cycloaddition. The belt-shaped structure and trans -stereochemistry of the alkene moieties of the octaphenyl[4.4]triphenylparacyclophane and a synthetic intermediate, 2,21-dioxo-11,30-diene[3.4.3.4]paracyclophane, were determined by X-ray crystallography. The synthetic methodology leading to octaphenyl[4.4]triphenylparacyclophane is applicable for the synthesis of substituted triphenylparacyclophanes and possibly their corresponding bis-hexabenzocoronenylparacyclophanes via a Scholl–Mullen oxidative aryl-aryl coupling reaction. [ABSTRACT FROM AUTHOR]

Certain cyclic sulfates (e.g. 23) together with various of their precursor sulfites (e.g. 21 and 22) have been prepared from the corresponding chiral, non-racemic bicyclo[2.2.2]octane-2,3-diols (e.g. 20). Such diols are obtained by engaging the corresponding enzymatically derived and enantiomerically enriched or homochiral cis -1,2-dihydrocatechol (e.g. 10) or certain derivatives in either inter- or intra-molecular Diels–Alder cycloaddition reactions. Other functionalities present within the title compounds can be chemoselectively manipulated without adversely affecting the associated sulfate residues. Enantiomerically enriched or homochiral cis -1,2-dihydrocatechols such as 10 have been elaborated via their Diels–Alder adducts (e.g. 20) and then the corresponding sulfites (e.g. 21 and 22) into the title compounds 23. [ABSTRACT FROM AUTHOR]

The synthesis of natural carbazoles O -demethylmurrayanine and murrastanine A starting from the title exo -heterocyclic diene- is described. In the synthesis of murrastanine A, its symmetric C4,C4′ dimer can be obtained as the sole product under rather mild conditions. In all cases, the key intermediate is the same diarylamine. The carbazole nucleus is obtained through a Pd-promoted cyclization of the appropriate diarylamine. For the synthesis of O -demethylmurrayanine, the cyclization takes place on a silylated derivative. The crystal structures of murrayanine, two diarylamines, and two non-natural carbazole intermediates are also presented. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comparative assessments of dimethylfuran-ethene DA reaction over metal phosphates. • Weak effects of acid type/strength and confinement when cycloaddition controls rate. • Cycloadduct dehydration reactivity benefits from increased Brønsted acid strength. • Catalyst mass effects on rates, selectivity and carbon balance elucidated in-depth. • Quantity/strength of acid sites systematically affect irreversible side reactions. Tandem Diels-Alder (DA) cycloaddition and dehydration reactions between bio-derived furans and dienophiles offer a sustainable route potentially able to meet the growing demands of aromatic chemicals worldwide. In particular, efforts to maximize the production of p-xylene from dimethylfuran (DMF) and ethene have led to an expanding list of solid acids with, reportedly, outstanding catalytic performances. In this work, we have revisited the kinetic complexities of this reaction that are characterized by a distinct shift in the rate-limiting step depending sensitively on catalyst mass, and addressed the possible origins of reactivity and selectivity trends across a range of solid acids that hold promise for the target reaction, including aluminosilicates and a series of mesoporous metal phosphate catalysts (MOPO x ; M = Sn, Ti, Zr, Hf, Nb and Ta), in both dehydration- and cycloaddition-limiting regimes. In contrast to initial p-xylene formation rates in the dehydration-limiting regime, which benefit from an increased acid strength of Brønsted acid sites, p-xylene formation rates within the cycloaddition-limiting regime are essentially unaffected by variations in acid site densities, Lewis and Brønsted acid strength, and pore confinement. Such weak dependences of DA reactivity on a multitude of acid properties provide strong hints that DA cycloaddition between DMF and ethene follows an inverse-electron-demand [4 + 2] route, most likely as a consequence of a more favorable adsorption of DMF than that of ethene on the acid sites enhancing so the electrophilicity of DMF, but not that of ethene as required by the normal-electron-demand cycloaddition. Product selectivities and carbon balances were tracked as functions of reaction time, conversion and reactant pressure or concentration to identify the side reactions and acid properties responsible for p-xylene selectivity losses and the ultimate formation of carbonaceous deposits. These findings deepen our understanding of the roles of Lewis acid sites and Brønsted acid sites for the chemical reactivities toward the DA cycloaddition, the consecutive cycloadduct dehydrative aromatization and undesired acid-catalyzed side reactions, and inform strategies to enhance DA reactivities and suppress deleterious side reactions from the standpoint of both materials and process design. [ABSTRACT FROM AUTHOR]

Recent reports have pointed out a sustainable and highly selective formation route via the Diels–Alder (DA) cycloaddition between biomass-derived 2, 5-dimethylfuran (DMF) and ethene over zeolitic catalysts to produce para-xylene (p -xylene). Here, a systematic multi-scale simulation was carried out to identify candidate zeolite frameworks with potentially better catalytic activities than previously reported catalysts, through a combination of " ab initio " synthesis, thermodynamic and kinetic analysis, and adsorption/diffusion simulations. We first screened representative zeolites based on the limiting dimensions of their voids (windows, cages, channels) for reactants and products, the extent of stabilization of the key transition states by organic structure directing agents, and the synthesis difficulty informed by literature knowledge. Subsequently, the intrinsic and apparent free energy barriers of the rate-determining step (i.e. , cycloaddition) obtained from density functional theory calculations were used to predict reaction kinetics of the potentially useful zeolites. Finally, three final candidates (MOR, MOZ, and IFR) and two experimentally validated zeolites (FAU and BEA) were employed to compare the adsorption and diffusion performance of DMF and p -xylene as the final criterion by grand canonical Monte Carlo and molecular dynamics simulations. In summary, MOR shows the fastest diffusion, IFR shows the lowest apparent energy barrier, and MOZ shows the lowest intrinsic energy barrier. Altogether, this study not only predicts MOR, IFR, and MOZ zeolites to have a good catalytic performance for the DA-dehydration process of DMF and ethene to p -xylene but also illustrates the potential of ab initio selection, through combined theoretical assessments of adsorption, reaction and diffusion, for the rational selection and design of optimal catalysts for targeted catalytic transformations. [Display omitted] • A fast screen was conducted to select the optimal zeolite for the DA cycloaddition process of the PX production. • Considering both reaction barrier and diffusion, MOZ, IFR, and MOR show better catalytic activity. • With suitable sizes, the 12 MR channels of MOZ, IFR, and MOR promote the reaction via vdW interaction. [ABSTRACT FROM AUTHOR]

In contrast to iodine(I)‐based halogen bond donors, iodine(III)‐derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro‐Michael addition reaction as well as in a Diels–Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)‐based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF3. [ABSTRACT FROM AUTHOR]

Aminocatalytic synthesis of highly enantiomerically enriched uracil derivatives bearing a bicyclo[2.2.2]octane scaffold is described. The developed strategy utilizes 1,3,6-trimethyl-5-formyluracil and α,β-unsaturated aldehydes as starting materials and has been realized employing various aminocatalytic activation strategies operating in a synergistic manner. The reaction cascade can be described as doubly cycloadditive as it consists of two consecutive Diels–Alder cycloadditions allowing for a facile construction of the bicyclo[2.2.2]octane scaffold. Notably, both steps proceed with dearomatization of the partially aromatic uracil moiety. Excellent stereoselectivity of the reaction cascade is ensured by the use of 2-(diphenylmethyl)pyrrolidine as aminocatalyst. [ABSTRACT FROM AUTHOR]

The substituted-9-bromo-9,10-dihydro-9,10-ethanoanthracenes ortho 8a-12a and meta 8b-13b have been synthesized via Diels-Alder reaction under microwave conditions. The cycloadduct isomers ortho 8a-11a and meta 8b-11b , with priority to o rtho 8a-11a , were obtained from the reaction of 9-bromoanthracene 1 with acrylonitrile 2 , 2-chloroacrylonitrile 3 , methacryloyl chloride 4 and acrylic acid 5, while ortho 12a and meta 12b , with priority to meta 12b , was obtained from the reaction of 9-bromoanthracene 1 with 1-cynao vinyl acetate 6. Interestingly, the only isomer meta 13b was obtained from the reaction of 9-bromoanthracene 1 with phenyl vinyl sulfone 7. The results proved that the steric or/and electronic nature of the dienophile substituent is/are playing significant roles in the regioselectivity and isomers ratio. [ABSTRACT FROM AUTHOR]

In contrast to iodine(I)‐based halogen bond donors, iodine(III)‐derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro‐Michael addition reaction as well as in a Diels–Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)‐based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF3. [ABSTRACT FROM AUTHOR]

Diels–Alder reactions have become established as one of the most effective ways to prepare stereochemically complex six‐membered rings. Different catalysis concepts have been reported, including dienophile activation by Lewis acids or H‐bond donors and diene activation by bases. Herein we report a new concept, in which an acidic prodiene is acidified by a Lewis acid to facilitate deprotonation by an imidazolium–aryloxide entity within a polyfunctional catalyst. A metal dienolate is thus formed, while an imidazolium–ArOH moiety probably forms hydrogen bonds with the dienophile. The catalyst type, readily prepared in few steps in high overall yield, was applied to 3‐hydroxy‐2‐pyrone and 3‐hydroxy‐2‐pyridone as well as cyclopentenone prodienes. Maleimide, maleic anhydride, and nitroolefin dienophiles were employed. Kinetic, spectroscopic, and control experiments support a cooperative mode of action. High enantioselectivity was observed even with unprecedented TONs of up to 3680. [ABSTRACT FROM AUTHOR]

We introduce the bioconjugation of polymers synthesized by RAFT polymerization, bearing no specific functional end group, by means of hetero‐Diels–Alder cycloaddition through their inherent terminal thiocarbonylthio moiety with a diene‐modified model protein. Quantitative conjugation occurs over the course of a few hours, at ambient temperature and neutral pH, and in the absence of any catalyst. Our technology platform affords thermoresponsive bioconjugates, whose aggregation is solely controlled by the polymer chains. [ABSTRACT FROM AUTHOR]

Alkylated waste vegetable oil is a versatile intermediate product in the synthesis of bio-based materials. Heterogeneous catalytic condition with high conversion rate in the direct alkylation of waste vegetable oil was reported and the deactivation mechanism of catalyst was revealed. The total exchange capacity, elemental composition and pyrolysis product of catalyst before and after the alkylation reaction were analysed by back titration, elemental analysis, electrospray ionization mass spectrometry, gas chromatography mass spectrometry and pyrolysis-gas chromatography/mass spectrometry, respectively. The results indicated that the metallic and non-metallic (C, H) elements contents of the catalyst have very much increased with great changes in pyrolysis product and a slight decrease in the total exchange capacity. The formation of insoluble polymers through Diels–Alder cycloaddition between triglycerides was proved to be the major factor causing the dysfunction of the catalytic centre. The metal ions from corrosion of the reactor were the minor factor causing about 2.56% loss of the catalytic centre. Moreover, the catalyst was able to maintain high catalytic efficiency when replacing the raw materials with other waste vegetable oil having low concentration of polyunsaturated fatty acids, which is significant for producing not only the aryl fatty acids derivatives but also the bio-based surfactants.

The parallel development of reversible deactivation radical polymerization and click reaction concepts significantly enriches the toolbox of synthetic polymer chemistry. The synergistic effect of combining these approaches manifests itself in a growth of interest to the design of well-defined functional polymers and their controlled conjugation with biomolecules, drugs, and inorganic surfaces. In this review, we discuss the results obtained with reversible addition–fragmentation chain transfer (RAFT) polymerization and different types of click reactions on low- and high-molar-mass reactants. Our classification of literature sources is based on the typical structure of macromolecules produced by the RAFT technique. The review addresses click reactions, immediate or preceded by a modification of another type, on the leaving and stabilizing groups inherited by a growing macromolecule from the chain transfer agent, as well as on the side groups coming from monomers entering the polymerization process. Architecture and self-assembling properties of the resulting polymers are briefly discussed with regard to their potential functional applications, which include drug delivery, protein recognition, anti-fouling and anti-corrosion coatings, the compatibilization of polymer blends, the modification of fillers to increase their dispersibility in polymer matrices, etc.

Phenyl, naphthyl, polyarylphenyl, coronene, and other aromatic and polyaromatic moieties primarily influence the final materials’ properties. One of the synthetic tools used to implement (hetero)aromatic moieties into final structures is Diels–Alder cycloaddition (DAC), typically combined with Scholl dehydrocondensation. Substituted 2-pyranones, 1,1-dioxothiophenes, and, especially, 1,3-cyclopentadienones are valuable substrates for [4 + 2] cycloaddition, leading to multisubstituted derivatives of benzene, naphthalene, and other aromatics. Cycloadditions of dienes can be carried out with extrusion of carbon dioxide, carbon oxide, or sulphur dioxide. When pyranones, dioxothiophenes, or cyclopentadienones and DA cycloaddition are aided with acetylenes including masked ones, conjugated or isolated diynes, or polyynes and arynes, aromatic systems are obtained. This review covers the development and the current state of knowledge regarding thermal DA cycloaddition of dienes mentioned above and dienophiles leading to (hetero)aromatics via CO, CO2, or SO2 extrusion. Particular attention was paid to the role that introduced aromatic moieties play in designing molecular structures with expected properties. Undoubtedly, the DAC variants described in this review, combined with other modern synthetic tools, constitute a convenient and efficient way of obtaining functionalized nanomaterials, continually showing the potential to impact materials sciences and new technologies in the nearest future.

A recent strong trend toward green and sustainable chemistry has promoted the intensive use of renewable carbon sources for the production of polymers, biofuels, chemicals, monomers and other valuable products. The Diels-Alder reaction is of great importance in the chemistry of renewable resources and provides an atom-economic pathway for fine chemical synthesis and for the production of materials. The biobased furans furfural and 5-(hydroxymethyl)furfural, which can be easily obtained from the carbohydrate part of plant biomass, were recognized as “platform chemicals” that will help to replace the existing oil-based refining to biorefining. Diels-Alder cycloaddition of furanic dienes with various dienophiles represents the ideal example of a “green” process characterized by a 100% atom economy and a reasonable E-factor. In this review, we first summarize the literature data on the regio- and diastereoselectivity of intermolecular Diels-Alder reactions of furfural derivatives with alkenes with the aim of establishing the current progress in the efficient production of practically important low-molecular-weight products. The information provided here will be useful and relevant to scientists in many fields, including medical and pharmaceutical research, polymer development and materials science.

In this paper, a DFT calculation was used to demonstrate the catalytic role of a WOX/SiO2 catalyst and show the excellent performance in 2,5-dimethylfuran to para-xylene conversion. A model of highly dispersed tungsten oxide supported on the amorphous silica was firstly constructed. A periodic DFT calculation was thereafter carried out to determine the reaction pathway, transition state (TS) and important intermediate structures. For reference purpose, the calculation was also repeat on an alkali ion, representative of a Lewis acid catalyst. Unexpectedly and although tungsten oxide is generally considered and characterized to be a Lewis acid, its mechanism for catalyzing the conversion of 2,5-dimethylfuran and ethylene to PX is differs significantly from other Lewis acids like alkali metal. Typical epoxide intermediates observed in other Lewis acid catalyzed systems are not formed over a WOX/SiO2 catalyst. The calculated reaction barrier indicated that the WOX/SiO2 catalyst has no obvious catalytic effect on the Diels–Alder cycloaddition for 2,5-dimethylfuran and ethylene. It mainly accelerates the dehydration step. The reason for the unique catalytic mechanism of WOX/SiO2 catalyst relies on the coordination of 2,5-dimethylfuran and tungsten that leads to the Diels–Alder cycloaddition that follow the so-called inverse electron demand mechanism. A new catalyst for this reaction was proposed based on the obtained mechanistic understanding. [ABSTRACT FROM AUTHOR]

[Display omitted] • The reaction routes of hydrochar formation from lignin-cellulose are established. • Kinetic and thermodynamic profiles of each reaction pathway are specified. • Hydrochar formation is controlled by the Diels-Alder and Pechmann reactions. • The Diels-Alder cycloaddition is endothermic and serves as intermediate mechanism. • The Pechmann condensation is endothermic and directly precipitates chromones. We investigated the kinetics and thermodynamics of the Diels-Alder cycloaddition and Pechmann condensation to evaluate the significance of both mechanisms toward hydrochar formation during hydrothermal carbonization and liquefaction of biomass. We performed well-designed experiments of semi-continuous hydrothermal conversion of pure compounds representative of lignin-cellulose fractions (i.e., D-(+)-cellobiose and 1-(3,4-dimethoxyphenyl)-2-(4-hydroxy-2-methoxyphenoxy)propane-1,3-diol) and corresponding hydrochar precursors at 220–370 °C for 60 min. We developed thermodynamically-feasible multi-phase reaction pathways and specified the kinetic and thermodynamic parameters of each pathway by fitting the reversible power-law kinetic model, Arrhenius equation, and correlation between conventional definition of Gibbs free energy and the Gibbs free energy isotherm equation into experimental data of time evolution of chemical species concentration measured using GC–MS, XRD, and μGC. Reaction pathways of mixtures of pure compounds were a combination of those for individual pure compounds. We discovered that endothermic Diels-Alder cycloaddition involving dienes and dienophile was prominent in D-(+)-cellobiose conversion pathways and functioned as an intermediate reaction producing precursors for various endothermic and exothermic precipitation mechanisms. The temperature dependence of solid organics formation via this indirect route depended on the net Δ H of a set of reaction pathways after Diels-Alder cycloaddition. In contrast, we found that the Pechmann condensation involving phenols and β-ketoester/β-ketoacid was significant in the conversion pathway of 1-(3,4-dimethoxyphenyl)-2-(4-hydroxy-2-methoxyphenoxy)propane-1,3-diol and facilitated direct precipitation of organics including 4,10-dimethyl-2,7-dioxo-2,7-dihydropyrano[2,3- g ]chromene-5-carbaldehyde and 4,5-dimethoxy-2,7-dioxo-6,7-dihydro-2 H -benzo[ g ]chromene-10-carboxylic acid. The endothermic nature of Pechmann condensation preferred higher temperatures for a higher equilibrium conversion toward solid product formation. Results in this study contributed to the improved understanding of fundamentals of hydrochar formation. [ABSTRACT FROM AUTHOR]

Four undescribed bis-iridoid glycosides, named phukettosides A–D, and one iridoid glycoside, referred to as phukettoside E, were isolated and fully characterized from the leaves of Morinda umbellata L. Phytochemical analysis also revealed the presence of eight known compounds. The structures were determined through extensive analysis of 1D and 2D-NMR spectroscopic and HRMS spectral data, and the absolute configurations of the isolates were deduced through ECD calculations. Biogenetic pathways for the bis-iridoid glycosides, phukettosides A–C, through intermolecular Diels-Alder type reactions, were proposed. The isolated compounds, with the exception of phukettosides B and D, were evaluated against a panel of cancer cell lines (MOLT-3, HuCCA-1, A549, HeLa, HepG2, and MDA-MB-231) and a non-cancerous cell line (MRC-5) for their cytotoxicity. None of the isolates had significant cytotoxic effects on the tested cell lines. [Display omitted] • Bis- and mono-iridoid glycosides were isolated from Morinda umbellata leaves. • The bis-iridoid glycosides probably arise from intermolecular Diels-Alder reactions. • The absolute configurations were confirmed by ECD calculation. • Cancer chemoprevention and the cytotoxicity of the isolates were evaluated. [ABSTRACT FROM AUTHOR]

The synthesis of linear alkylbenzenes (LABs) from biomass-derived furan and linear alkenes via Diels−Alder cycloaddition followed by acid-catalyzed dehydration is presented. Furan was reacted with 1-dodecene, the alkene model compound, over the niobic acid catalyst in a laboratory-scale batch reactor. The effects of reaction temperature, catalyst loading, and initial reactant ratio were systematically investigated. Our experiments reveal that 1-alkene isomerization, furan alkylation to produce dodecylfuran, and self Diels−Alder cycloaddition of furan to produce benzofuran are the major side reaction pathways competing with LAB production. The highest conversion of 1-dodecene to 1-phenyldecane, our target LAB, was found to be at approximately 12 mmol/mol. The main reasons for this low LAB yields include high furan activity and volatility, coke formation, and mass transfer limitations. Despite low LAB yields, our work demonstrates for the first time that it is possible to synthesize LABs from biomass-derived furan and linear alkenes over solid acid catalysts.

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A–C (1–3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two “meta” products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were “ortho” products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.

The injection (or removal) of electrons into (or from) a substrate by an electrode can effectively catalyze various redox‐neutral reactions that otherwise require harsh conditions and/or the use of reagents. Such processes involve the electrogeneration of an ionic or radical ionic species, which after a coupled chemical step either undergoes a backward electron exchange with the electrode (ECEb mechanism) or triggers a chain process in the bulk solution. Under these circumstances, sub‐stoichiometric amounts of charge are sufficient to achieve a full conversion and conceptionally, the electrons and holes can be understood as being catalysts. This principle has been successfully applied to accomplish a number of redox‐neutral transformations such as molecular rearrangements, Diels‐Alder‐type cycloadditions and radical substitution reactions (SRN1) in a mild and atom‐economical fashion. Although examples have been reported but sporadically since the early 1970s, a number of exciting recent developments have led us to review and discuss these cases using unifying mechanistic concepts that are described herein. [ABSTRACT FROM AUTHOR]

Graphical abstract A proposed catalytic strategy for the production of aromatic hydrocarbons by co-feeding bio-derived furans and methanol in a continuous flow fixed-bed reactor over HZSM-5 (Si/Al = 25) at moderate temperature. Highlights • A method for converting bio-derived furans to aromatics was demonstrated. • Methanol could efficiently suppress the coke formation. • Aromatic hydrocarbons was obtained with a maximum yield of 42.0 C-mol%. Abstract In this paper, we study the production of aromatic hydrocarbons by co-feeding furans and methanol in a continuous flow fixed-bed reactor over HZSM-5 at 400–600 °C. The effects of reaction temperature, weight hourly space velocity (WHSV), furan to methanol molar ratio and time on stream on the product distribution were investigated. Maximum aromatics yield of 42.0% was obtained over HZSM-5 (Si/Al = 25) with 2-methylfuran (MF) to methanol molar ratio of 1:5 at 500 °C. With the methanol to MF molar ratio increasing from 0 to 5, the conversion of MF increased from 64.7% to 100.0% and the yield of coke decreased from 22.3% to 11.4%. In this process, dimethyl ether derived from methanol dehydration could promote the conversion of MF to aromatic hydrocarbons via Diels-Alder reaction. HZSM-5 with Si/Al ratio of 25 exhibited superior catalytic activity, indicating that strong acidity was necessary for the coupling conversion of MF and methanol. Additionally, the coupling conversions of 2,5-dimethylfuran (DMF), furfural (FF) and furfuryl alcohol (FA) and methanol were investigated. Functional groups of furan rings did not change the formation pathway of aromatic hydrocarbons but they have different constraints on the Diels-Alder reaction of furan ring with olefins. [ABSTRACT FROM AUTHOR]

A concise and highly stereoselective total synthesis of the Daphniphyllum alkaloids (−)‐daphenylline has been accomplished. The synthesis was started from (S)‐carvone and proceeded via a stereoselective Mg(ClO4)2‐catalyzed intramolecular amide addition cyclization, an intramolecular Diels–Alder reaction to construct the ABCD tetracyclic core architecture, and a Robinson annulation coupled with an oxidative aromatization sequence. Finally, the DF ring system was installed through an intramolecular Friedel–Crafts cyclization. The total synthesis of (−)‐daphenylline is achieved in 19 steps in the longest reaction sequence and in 7.6 % overall yield. Round, round, get around: A concise and highly enantioselective total synthesis of (−)‐daphenylline was accomplished in 19 steps and 7.6 % overall yield from (S)‐carvone. It features an Mg(ClO4)2‐catalyzed intramolecular amide cyclization and a Diels–Alder cycloadditon to construct the tetracyclic motif, a tandem Robinson annulation with oxidative aromatization, and an intramolecular Friedel–Crafts acylation and Nazarov‐type cyclization to construct the DF rings. [ABSTRACT FROM AUTHOR]

Structural designs combining oligoparaphenylene‐derived nanohoops with other functional organic building blocks should lead to novel molecular architectures with intriguing properties. Herein, we describe the synthesis of a pentiptycene‐derived chiral dual nanohoop molecule with key steps including ring expansion through dianthracene cycloreversion and transannular [4+2] cycloaddition across a 64‐membered macrocycle. The crystal structure of the nanohoop molecule displays an ordered packing pattern with long‐range channels in the solid state. Furthermore, nonracemizable enantiomers of the nanohoop were obtained through resolution and exhibited promising chiroptical properties. Across the great divide: A pentiptycene‐derived chiral dual nanohoop has been synthesized through dianthracene cycloreversion followed by transannular cycloaddition across the resulting 64‐membered macrocycle (see scheme). The nanohoop molecule displays long‐range channels in the solid state and promising chiroptical properties after resolution. [ABSTRACT FROM AUTHOR]

A series of renewable novel bicyclic AB type polyester precursors have been prepared in good overall yield from lignocellulosic biomass. These advancements take full advantage of the differing oxidation states of functional groups in 5-(hydroxymethyl)furfural by chemoselective preparation of furanic hydroxy esters and applying benzyne-Diels–Alder cycloaddition/aromatization strategies. [ABSTRACT FROM AUTHOR]

π-Conjugated molecules are the active materials in organic electronics, yet the range of available materials is limited by the nontrivial, multistep synthetic process required to obtain long π-conjugated backbones. Here, Diels–Alder cycloaddition and its reactivity and selectivity are evaluated as a means for obtaining long, novel, π-conjugated backbones. Particular attention is paid to the Diels–Alder conjugation products of furans, such as selectively substituted arenes and, potentially, carbon nanoribbons. [ABSTRACT FROM AUTHOR]

The cytochalasans are a large family of polyketide natural products with potent bioactivities. Amongst them, the aspochalasins show particularly intricate and fascinating structures. To gain insight into their structural diversity and innate reactivity, we have developed a rapid synthesis of aspochalasin D, the central member of the family. It proceeded in 13 steps starting from divinyl carbinol and utilized a high pressure Diels–Alder reaction that features high regio‐ and stereoselectivity. So far, our work has culminated in a biomimetic synthesis of aspergillin PZ, an intricate pentacyclic aspochalasan. Delivering under pressure: The cytochalasans are a large family of polyketide natural products with fascinating structures and potent bioactivities. Described is a rapid synthesis of aspochalasin D, the central member of this family. It proceeds in 13 steps starting from divinyl carbinol and utilized a high pressure Diels–Alder reaction. So far, this work has culminated in a biomimetic synthesis of aspergillin PZ, an intricate pentacyclic aspochalasan. [ABSTRACT FROM AUTHOR]