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Ultrafast tunnel ionization enables femtosecond time-resolved dynamic measurements of the retro-Diels–Alder reactions of positively charged cyclohexene, norbornene, and dicyclopentadiene. Unlike the reaction times of 500–600 ps that are observed following UV excitation of neutral species, on the ionic potential energy surfaces, these reactions occur on a single picosecond timescale and, in some cases, exhibit vibrational coherence. In the case of norbornene, a 270 cm−1 vibrational mode is found to modulate the retro-Diels–Alder reaction. [ABSTRACT FROM AUTHOR]

Photoreaction of pyrene 1 with methyl cinnamate 15a gave a photocycloadduct 16a at 4,5-position of pyrene stereoselectively. Oxidation of 16a using DDQ yielded a pyrenocyclobutene derivative 18a. Functional group conversion of the ester moiety of 18a resulted in the synthesis of carboxylic acid 19, alcohols 20 and 21, sulfonate 23, and methylenecyclobutene 24. Diels–Alder reactions of 18a with electron-deficient alkenes or alkynes 25a–f afforded cycloadducts, pyrenocyclohexenes 26a–c and pyrenocyclohexadienes 26e, f stereoselectively in good yields. Thermal reactions of pyrenocyclobutene-linked electron-deficient alkenes 22a, b produced 4-benzyl-5-alkenylpyrenes 29a, b via ring cleavage followed by 1,5-hydrogen transfer.

The first total synthesis of heavily oxidized cassane‐type diterpenoid neocaesalpin A (1) is disclosed. At the heart of the synthesis lies an intermolecular Diels–Alder reaction that rapidly assembles the target framework from commercial materials. A carefully orchestrated sequence of oxidations secured the desired oxygenation pattern. Late‐stage release of the characteristic butenolide occurred through a novel mercury(II)‐mediated furan oxidation. Successful extension of the route allowed preparation of neocaesalpin AA (2) as well as nominal neocaesalpin K (3) and suggested structural revision of neocaesalpin K, leading to the hypothesis that the two are likely the same natural product with correct assignment as 2. [ABSTRACT FROM AUTHOR]

In this paper, we report an alternative approach to the targeted -oxyallylboronate: a copper-catalyzed 1,4-acylboration of , -unsaturated esters with B SB 2 sb pin SB 2 sb and pivalic anhydride is described (Scheme 1c). H SB 2 sb O SB 2 sb under acetate buffer conditions [11] furnished the corresponding allylic alcohol B 4 b with maintenance of the ketene acetal moiety, which can be a good synthetic handle for further manipulations. The ligand gave a large impact on the yield and I E/Z i selectivity, with the electron-withdrawing monodentate P(3,5-(CF SB 3 sb ) SB 2 sb C SB 6 sb H SB 3 sb ) SB 3 sb proving to be best (entries 1-5). Keywords: allylboronate; borylation; conjugate addition; copper; stereoselectivity EN allylboronate borylation conjugate addition copper stereoselectivity 2205 2209 5 10/31/23 20231127 NES 231127 Graph Allylborons constitute an important class of organoboron compounds in modern synthetic organic chemistry because they enable the chemo- and stereoselective allylation of organic molecules, after which the resulting allyl moiety can be transformable with high diversity. [Extracted from the article]

α,α′-Dioxothiones are very reactive species and can participate in cycloaddition reactions with several compounds. Porphyrins bearing vinyl groups are interesting scaffolds for further functionalization namely by cycloaddition reactions; it is well known that porphyrins can react as either a 2π or 4π component in different cycloaddition approaches, such as hetero Diels–Alder reactions. This study reports for the first time the reactivity of a α,α′-dioxothione in the presence of 5,10,15,20-tetraphenylporphyrin bearing a vinyl group (2-VinylTPP) and of its Zn(II) complex (Zn-VinylTPP). The results revealed that the reactivity of α,α′-dioxothione as a heterodienophile or as a heterodiene is dependent on the absence or on the presence of Zn(II) in the porphyrin inner core. Thus, the free base 2-VinylTPP reacted as a diene affording two diastereomeric chlorins (3a and 3b) that are in a tautomeric equilibrium with porphyrin 4, and Zn-VinylTPP reacted as a dienophile affording porphyrin 5 and different oxidized products. All the cycloadducts obtained were revealed to be emissive in the red region and be able to produce 1O2. [ABSTRACT FROM AUTHOR]

Despite advances in the development of catalytic asymmetric Diels‐Alder reactions, introducing α,β‐unsaturated esters as dienophiles remains challenging owing to their low reactivity. Herein, we report that a chiral aminocatalyst in conjunction with a chiral isothiourea catalyst or a Brønsted acid can promote enantio‐ and diastereoselective Diels‐Alder reactions between 2,4‐dienals and α,β‐unsaturated esters. This method proceeds through the formation of chiral trienamine intermediates for the exo‐cycloaddition with activated dienophiles, α,β‐unsaturated acylammonium species or protonated N‐heteroaryl‐substituted alkenes. Through synergistic activation of both dienes and ester dienophiles, densely functionalized cyclohexenes bearing multiple stereocenters can be afforded with up to >25:1 dr and >99% ee. Moreover, we show that variation of the configurations of the chiral catalysts and the olefin geometry allows the stereodivergent preparation of four stereoisomers of the enantiopure exo‐products. [ABSTRACT FROM AUTHOR]

The formal aza‐Diels‐Alder reaction of dihydro‐β‐carboline with heterodiene mediated by caesium carbonate has been described. This pathway provided a mild approach to functionalized polycyclic frameworks in 41%–91% yields. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra‐epi‐UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, from which members with potent antibacterial, antifungal, and anticancer activities have been identified. Our approach features a tandem carbonylative Stille cross coupling and Diels‐Alder reaction to forge a key C—C bond and build the trans‐decalin system. This tandem process utilizes carbon monoxide as a one‐carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels‐Alder cyclization. Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone‐containing polyketides. [ABSTRACT FROM AUTHOR]

Cyclodextrins have been utilized as molecular capsules in pharmaceutical application. Cyclodextrin dimers exhibited the property of including larger compounds than cyclodextrin monomers. The fabrication of cyclodextrin dimers is challenging as it involves complicated synthesis and purification techniques. In this study, cyclodextrin dimers were synthesized via a facile procedure using the Diels–Alder reaction to construct a linker between two cyclodextrin units. Furan-substituted γ-CD and maleimide-substituted α-CD and γ-CD were efficiently synthesized in high yields. The furan- and maleimide-substituted cyclodextrins combined to form the desired dimers in water at 25 °C. The dimers disassembled at 75 °C via the retro-Diels–Alder reaction yielding furan and maleimide cyclodextrin monomers, confirmed using 1H NMR spectroscopy. The γ-CD-γ-CD dimer exhibited a high binding constant for tropaeolin OO due to having a wider and more suitable cavity than the monomers. The Diels–Alder reaction can be an efficient strategy for constructing cyclodextrin dimers possessing inclusion abilities. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra‐epi‐UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, from which members with potent antibacterial, antifungal, and anticancer activities have been identified. Our approach features a tandem carbonylative Stille cross coupling and Diels‐Alder reaction to forge a key C—C bond and build the trans‐decalin system. This tandem process utilizes carbon monoxide as a one‐carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels‐Alder cyclization. Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone‐containing polyketides. [ABSTRACT FROM AUTHOR]

An unprecedented phosphine-catalyzed formal Buchner [6+1] annulation of a newly designed allenoate has been developed, providing a series of cycloheptatriene derivatives in moderate to good yields (up to 99%). This reaction demonstrates that the introduction of an electrophilic allylic group to allenoates effectively extends the reaction scope of phosphine-catalyzed annulation, providing a concise route to cycloheptatrienes. Mechanistic study indicated that this reaction involves a [4+2] Diels–Alder reaction and ring expansion of the bicyclo[4.1.0] moiety, which is similar to the Buchner reaction. Notably, an enantioselective variant of this [6+1] annulation can also be performed using a chiral iminophosphine catalyst. [ABSTRACT FROM AUTHOR]

In attempts to make octaphenyldibenzofuran (7) and octaphenyldibenzothiophene (8), 2,5‐dibromofuran (4) and 2,5‐dibromothiophene (5), respectively, were heated with tetracyclone (2) under forcing conditions, but only single addition products, such as 2‐bromo‐4,5,6,7‐tetraphenylbenzofuran (10) and 2‐bromo‐4,5,6,7‐tetraphenylbenzothiophene (12) were observed. However, when 2,5‐dibromothiophene‐1,1‐dioxide (6) was heated with tetracyclone, the chief product was 1,2,3,4,6,7,8‐heptaphenyltriphenylene (14). Similarly, when compound 6 was heated with acecyclone (15), the product was 11,18,20‐triphenyldiacenaphtho[a,h]triphenylene (16). Both 14 and 16 have been characterized by X‐ray crystallography. They are proposed to form from double Diels‐Alder addition products of the cyclopentadienones by extrusion of sulfur dioxide and rearrangement of the resulting radicals. [ABSTRACT FROM AUTHOR]

The resonance effect happens in very number of natural oscillators and very important in a lot of phenomena. In the surface of a hydride metal, the resonance effect causes the kinetic energy of electrons is increased until they can cooperate inverse−β interaction. This reaction can be done in the electrolysis of palladium and platinum in water electrolyte. In this research, a new method for calculating the rate of inverse−β interaction is introduced. This method is based on the Feynman equations that is more understandable and simpler compared to other methods. The inverse−β interaction is created by high energy electrons. Surface electrons accelerate by resonance effect which it is produced by electrolysis process. The atomic electrons of metal behave as a forced oscillator with very small damping which cause the resonance effect. We will indicate this resonance effect is satisfied by the new equations. The theoretical results have good agreement with experimental results. [ABSTRACT FROM AUTHOR]

The Diels Alder (D-A) reaction represents a crucial component of fundamental organic chemistry education and serves as a quintessential example of structural chemistry analyzed via basic principles of chemical sciences. This study explores the Diels-Alder reaction involving 1-methoxy-1,3-butadiene and acrolein, utilizing tools such as the Hückel molecular orbital (HMO) method, frontier molecular orbital (FMO) theory, and quantum chemical calculations. This approach provides detailed quantitative data and intuitive visual illustrations to elucidate the stereospecificity, regioselectivity, and stereoselectivity inherent to this reaction. The findings from this study serve as valuable resources for students, not only enhancing their understanding of D-A reaction properties and principles, but also developing their interest in computational chemistry and augmenting their problem-solving acumen. [ABSTRACT FROM AUTHOR]

Acrylates are well known electrophilic alkenes having multitude of applications in organic synthesis. They are very good acceptors in Michael addition reactions and are good enophile/dienophile/dipolarophile partners in cycloaddition reactions. Replacing the β‐alkyl/aryl groups in acrylates by a silicon group would be interesting. In addition to the conventional reactions displayed by acrylates, β‐silylacrylates (β‐SAs) can show reactivity specifically related to the silicon group. Many conventional organic reactions such as hydrodimerization, organocatalytic asymmetric Michael additions, inter‐ and intra‐molecular Diels–Alder reactions, and asymmetric 1,3‐dipolar cycloadditions have been used to generate the complex chemical entities from β‐SAs. Some of the reaction outcomes were vastly influenced by the silicon substituent. This review describes the practical synthesis β‐SAs and their use as starting point in complex molecule generation including total synthesis of some natural products/bioactive molecules. [ABSTRACT FROM AUTHOR]

The 5,8-disubstituted indolizidines are the largest family of indolizidines isolated from the skin of amphibians. These compounds exhibit interesting biological activities such as noncompetitive blockers of nicotinic receptors. In this paper, we present a short, simple, and general synthesis of these alkaloids based on the hetero Diels–Alder reaction between suitable monoactivated dienes and Δ1-pyrroline as the dienophile. The selectivity of the process is explained based on computational studies. Concise synthesis of the indolizidine alkaloid 181B from a hetero Diels–Alder reaction was accomplished in four steps. [ABSTRACT FROM AUTHOR]

An efficient synthetic method for multisubstituted naphthalenes from 4-hydroxy-2-pyrones through cycloaddition with aryne intermediates is disclosed. Various highly functionalized 2-pyrones were synthesized through 4-hydroxy-2-pyrones in short steps. The resulting 2-pyrones reacted smoothly with a wide range of aryne intermediates generated from o-silylaryl triflates to provide multisubstituted naphthalenes by the Diels–Alder reaction and following decarboxylative aromatization. The aryne reaction of 2-pyrones served in the synthesis of diverse naphthalenes having 1,2,3-triazole moieties by combination with triazole formation of 4-azido-2-pyrones. [ABSTRACT FROM AUTHOR]

Herein we report the first example of a supramolecular cage that works as a catalytic molecular reactor to perform transformations over fullerenes in aqueous medium. Taking advantage of the ability of metallo–organic Pd(II)‐subphthalocyanine (SubPc) capsules to form stable host:guest complexes with C60, we have prepared a water‐soluble cage that provides a hydrophobic environment for conducting cycloadditions over encapsulated C60, namely, Diels–Alder reactions with anthracene. Indeed, the presence of catalytic amounts of SubPc cage dissolved in water promotes co‐encapsulation of insoluble C60 and anthracene substrates, allowing the reaction to occur inside the cavity under mild conditions. The lower stability of the host:guest complex with the resulting C60 cycloadduct facilitates its displacement by pristine C60, which grants catalytic turnover. Moreover, bis‐addition compounds are regioselectively formed inside the cage when using excess anthracene. [ABSTRACT FROM AUTHOR]

The highly enantioselective organocatalytic synthesis of spirocyclic compounds by Diels‐Alder reactions via trienamine using cyclic 2,5‐dienones as bisvinylogous precursors and different nitroalkenes as dienophiles is described. The use of cinchonidine‐based primary amine as catalyst and benzoic acid as co‐catalyst has allowed the construction of a wide variety of spiro compounds containing three stereogenic centres in good yields and excellent diastereo‐ and enantioselectivities. Additionally, other dienophiles have been evaluated exhibiting different behaviour depending on the electron withdrawing group nature. Subsequent transformations have yielded complex structures with up to five stereocentres. The plausible reaction mechanism has been investigated by computational methods. [ABSTRACT FROM AUTHOR]

Domino Knoevenagel‐cyclization reactions of 2H‐chromene and chroman derivatives containing o‐formylaryl amine or ether side‐chain was carried out to produce four series of chiral condensed heterocycles representing four novel skeletons and exhibiting antiproliferative activity. The cyclization step occurred with four different mechanisms: a concerted intramolecular hetero Diels‐Alder reaction (IMHDA), a stepwise polar [2+2] cycloaddition, a [1,5]‐hydride shift‐6‐endo cyclization or a multi‐step nitro hetero Diels‐Alder‐ring‐opening‐Cadogan‐type cyclization sequence. The latter reaction provided a new route to hydroxyindoles by an inverse Cadogan‐type cyclization, in which the nitro group is deoxygenated by a nitro IMHDA‐ring‐opening sequence. The cyclization mechanisms and their stereoselectivity were studied by DFT calculations, based on which we proposed a mechanism for the multi‐step cyclization to hydroxyindoles and explained the observed diastereoselectivity. [ABSTRACT FROM AUTHOR]

We have disclosed a Rauhut–Currier reaction of γ-alkyl-substituted allenoate, catalyzed by L -valine-derived amide phosphine, to form trisubstitued allenoate, which was trapped by maleimide or DMAD via the Diels–Alder reaction. Exo-bicyclic succinimide derivatives including three continuous stereocenters with an exo-carbon–carbon double bound were constructed in up to quantitative yields with high stereospecificity. [ABSTRACT FROM AUTHOR]

Copper ferrite nanoparticles efficiently transformed the unreactive aromatic chalcones into activated dienophiles for a Diels–Alder reaction with cyclopentadiene/isoprene as dienes. The best results in terms of rate of reaction and product yields were obtained in an eco-friendly solvent i.e. ethanol using 5 mol% catalytic loading. Substrate scope was also investigated for a number of chalcone derivatives, and all the reactions proceeded smoothly to provide the corresponding DA adducts in high yields (up to 89%) and good diastereoselectivities (up to >99%) with endo-preference. [ABSTRACT FROM AUTHOR]

Recyclability of cross‐link polymer materials is essential to alleviate environmental pollution caused by discarded or damaged polymers. Herein, a facile method for producing recyclable polyamide materials is developed. Linear polymer chains are constructed by Schiff base reaction between glutaraldehyde (GD) and furandiamine (FD). The linear polymer chains are crosslinked by bismaleimide (BM) to give rise to polyamide material, named GF‐BMs. The resulting GF‐BMs polyamide material possesses strong tensile strength (78 MPa) and good solvent resistance from room temperature to 135 °C. Especially, the thermally reversible Diels–Alder covalent bonds and dynamic imine bonds in the polymer network have a synergistic effect on fast‐reprocessing, self‐healing, and recyclability, which provides a new idea for recyclable materials. [ABSTRACT FROM AUTHOR]

Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita–Baylis–Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 dr). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2′-[1,3]oxazino[2,3-a]isoquinoline] and spiro[indene-2,1′-pyrrolo[2,1-a]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

In the present work, the bond breaking/forming events along the intramolecular Diels–Alder (IMDA) reaction of (2E,4Z,6Z)-2(allyloxy)cycloocta-2,4,6-trien-1-one have been revealed within bonding evolution theory (BET) at the density functional theory level, using the M05-2X functional with the cc-pVTZ basis set. Prior to achieving this task, the energy profiles and stationary points at the potential energy surface (PES) have been characterized. The analysis of the results finds that this rearrangement can proceed along three alternative reaction pathways (a–c). Paths a and b involve two steps, while path c is a one-step process. The first step in path b is kinetically favored, and leads to the formation of an intermediate step, Int-b. Further evolution from Int-b leads mainly to 3-b1. However, 2 is the thermodynamically preferred product and is obtained at high temperatures, in agreement with the experimental observations. Regarding the BET analysis along path b, the breaking/forming process is described by four structural stability domains (SSDs) during the first step, which can be summarized as follows: (1) the breaking of the C–O bond with the transfer of its population to the lone pair (V(O)), (2) the reorganization of the electron density with the creation of two V(C) basins, and (3) the formation of a new C–C single bond via the merger of the two previous V(C) basins. Finally, the conversion of Int-b (via TS2-b1) occurs via the reorganization of the electron density during the first stage (the creation of different pseudoradical centers on the carbon atoms as a result of the depopulation of the C–C double bond involved in the formation of new single bonds), while the last stage corresponds to the non-concerted formation of the two new C–C bonds via the disappearance of the population of the four pseudoradical centers formed in the previous stage. On the other hand, along path a, the first step displays three SSDs, associated with the depopulation of the V(C2,C3) and V(C6,C7) basins, the appearance of the new monosynaptic basins V(C2) and V(C7), and finally the merging of these new monosynaptic basins through the creation of the C2–C7 single bond. The second step is described by a series of five SSDs, that account for the reorganization of the electron density within Int-a via the creation of four pseudoradical centers on the C12, C13, C3 and C6 carbon atoms. The last two SSDs deal with the formation of two C-C bonds via the merging of the monosynaptic basins formed in the previous domains. [ABSTRACT FROM AUTHOR]

The present work is focused on polyester resins obtained from the diglycidyl ether of bisphenol A and anthracene modified 5-maleimidoisophthalic acid. Because the maleimide-anthracene Diels–Alder (DA) adduct is stable at high temperatures, it is considered a good option for high performance polymers. However, the information related to the retroDA reaction for this type of adduct is sometimes incoherent. A detailed thermal study (conventional TGA, HiRes TGA, MTGA, DSC, MDSC) was performed in order to establish whether the rDA reaction can be revealed for this type of anthracene modified polyester resins. The TGA method confirmed the cleavage of the anthracene–maleimide DA adduct, while the DSC demonstrated the presence of anthracene in the system. At high temperatures, unprotected maleimide homopolymerizes and/or reacts with allyl groups according to the –ene reaction. Therefore, the thermal DA reaction is not displayed anymore upon the subsequent cooling, and the glass transition region is registered at a higher temperature range during the second heating. The use of sample-controlled thermal analysis (HiRes TGA) and MTGA improved the TGA result; however, it was not possible to separate the very complex degradation processes that are interconnected. [ABSTRACT FROM AUTHOR]

The interest in bio‐based alternatives to classical polyesters such as poly(ethylene terephthalate) (PET) and poly(butylene terephthalate) (PBT) is steadily growing to achieve a more sustainable approach to polymer materials. In this study, PBT/poly(butylene furanoate) (PBF) blends are prepared, characterized and extrusion foamed. PBF as a bio‐based polyester offers two advantages. The ecological footprint of the material is reduced, and additionally, it can be used in Diels‐Alder reactions at the blend surface to support fusion of the foamed beads. The blending behavior of the polyesters is investigated using samples prepared in a microcompounder, particularly focused on the miscibility of the blends and transesterification reactions. The blends are thermodynamically immiscible but show a certain degree of transesterification according to nuclear magnetic resonance (NMR) spectroscopy. The morphology of blend beads produced by an extrusion foaming process is analyzed regarding their cell density, cell size distribution, and open‐cell content. It is shown that PBF has a positive effect on the bead foam morphology. The use of a bifunctional linker designed for chemical fusion of the bead surfaces allows to obtaining of molded parts, in contrast to beads containing pure PBT. [ABSTRACT FROM AUTHOR]

Dehydrohalogenation of 1,4‐dihalobenzenes and 1,2,4‐trichlorobenzene is performed using n‐BuLi to form benzynes. These benzynes are used as dienophiles in a Diels–Alder reaction with the dienes furan and 2,5‐dimethylfuran to prepare new benzonorbornadiene derivatives. The cycloadducts of furan are polymerized by a ring‐opening metathesis reaction using a Hoveyda–Grubbs ruthenium catalyst. The polymers are characterized by 1H NMR (nuclear magnetic resonance), and unambiguous proton chemical shift assignments are based on the multiplicity pattern of proton resonances. This is confirmed by 2D NMR data from HSQC(Heteronuclear Single Quantum Coherence) and COSY (Correlation Spectroscopy) spectra. The polybenzonorbornadienes have both cis and trans conformation in their chemical structure. The trans conformation is qualitatively in greater proportion observed at 1H NMR experiments. These materials may have syndiotactic microstructure by the lack of correlations in COSY. [ABSTRACT FROM AUTHOR]

The role of the Cr(CO)3 coordination to the aromatic ring of naphtoquinone (NQ) in the polar Diels-Alder (P-DA) reactions with cyclic dienes, cyclopentadiene (Cp), cyclohexadiene (Ch), and 1-methoxy-cyclohexadiene (ChOMe), has been studied within Molecular Electron Density Theory (MEDT). Electron Localization Function (ELF) of the NQ:Cr(CO)3 complex indicates that Cr(CO)3 does not cause any remarkable change in the electronic structure of NQ. While the NQ:Cr(CO)3 complex is categorized as a strong electrophile, the cyclic dienes are categorized as strong nucleophiles, suggesting P-DA reactions. Formation of the NQ:Cr(CO)3 complex reduces the activation energy by only 0.7 kcal·mol−1. While Ch shows a lower reactivity than Cp, ChOMe presents the highest reactivity of this series of cyclic dienes. Analysis of the activation Gibbs free energies of the P-DA reaction with Cp indicates that the reaction is completely endo and anti stereoselective. The present MEDT study shows that the Cr(CO)3 complex has no effective catalytic activity in the P-DA reactions of NQ with cyclic dienes, but only permits the reaction to take place experimentally with a total endo and anti facial stereoselectivity, yielding a single cycloadduct. [ABSTRACT FROM AUTHOR]

Selective linear 1,3‐dienylations are essential transformations, and numerous synthetic efforts have been documented. However, a general method enabling access to electron‐rich, ‐poor, and biologically relevant dienyl molecules is in high demand. Hence, we report a straightforward method of manganese(I)‐catalyzed C−H dienylation of arenes by using iso‐pentadienyl carbonate as a five carbon synthon. This is a highly unprecedented report for selective linear 1,3‐dienylation using manganese C−H activation catalysis. Our method facilitates the synthesis of varieties of dienes, including those suitable for normal or inverse electron demand Diels‐Alder reactions, dienyl glycoconjugates, and unnatural amino acids. Extensive mechanistic studies, including isolation of C−H activated organo‐manganese complex and isotopic analyses, have supported the proposed mechanism of this dienylation. The synthetic applicability of this method eased to deliver a 6/6/5‐fused tricyclic nagilactone scaffold. [ABSTRACT FROM AUTHOR]

Herein, we present a novel and metal‐free approach to the stereospecific synthesis of E‐stilbenes. Starting from substituted 6‐arylhexa‐3,5‐dien‐2‐ones, a multicomponent enolacetylation/intermolecular Diels–Alder reaction was performed using ethyl acetate as a green solvent. The obtained cycloadducts were then oxidized without purification to produce the stilbenic products in good yields up to 67 % and with complete (E)‐stereospecificity and regioselectivity. Moreover, heterostilbenes were synthetized using this approach, displaying the potential applications of this protocol in pharmaceutical and material sciences. The proposed methodology was further extended to the synthesis of diarylacetylenes, furnishing a new metal‐free synthetic access to this important class of compounds. Furthermore, DFT calculations were performed confirming a concerted [4+2] reaction mechanism of the key ring‐forming step. At last, the energetic analysis of the possible transition states helps to shed some light on the experimentally observed total regio‐ and chemoselectivity. [ABSTRACT FROM AUTHOR]

Oriented external electric fields (EEFs) act as catalysts that can induce selectivity in chemical reactions. The responses of the Diels–Alder (DA) reaction between butadiene and ethylene (BDE‐DA) as well as cyclopentadiene and ethylene (CPDE‐DA) towards EEF stimuli are investigated here using density functional theory (B3LYP) calculations. EEF is a vector that catalyzes the reaction in one direction while inhibiting it in the opposite direction. Here we report that the inhibitive direction becomes rate‐enhancing after some increase in the EEF. The EEF value that brings about the maximum possible inhibition for the reaction is defined as the electrostatic resistance point (ERP). The possibility of both normal and inverse electron‐demand DA reactions causes catalytic activity in both directions of the EEF starting at a unique ERP value. The C5 substituents of cyclopentadiene control the ERP values depending upon the resistance power that the functional group provides against the EEF. The endo and exo diastereomeric transition states of the DA reaction have distinct ERP values and the difference (ΔERP) provides the through‐space electrostatic contribution to the stereoselectivity on a relative scale. Thus, the ERP values can be used as a gauge for the electrostatic interactions between substituent groups and external stimuli. [ABSTRACT FROM AUTHOR]

The metabolic labeling of nucleic acids in living cells is highly desirable to track the dynamics of nucleic acid metabolism in real‐time and has the potential to provide novel insights into cellular biology as well as pathogen‐host interactions. Catalyst‐free inverse electron demand Diels–Alder reactions (iEDDA) with nucleosides carrying highly reactive moieties such as axial 2‐trans‐cyclooctene (2TCOa) would be an ideal tool to allow intracellular labeling of DNA. However, cellular kinase phosphorylation of the modified nucleosides is needed after cellular uptake as triphosphates are not membrane permeable. Unfortunately, the narrow substrate window of most endogenous kinases limits the use of highly reactive moieties. Here, we apply our TriPPPro (triphosphate pronucleotide) approach to directly deliver a highly reactive 2TCOa‐modified 2′‐deoxycytidine triphosphate reporter into living cells. We show that this nucleoside triphosphate is metabolically incorporated into de novo synthesized cellular and viral DNA and can be labeled with highly reactive and cell‐permeable fluorescent dye‐tetrazine conjugates via iEDDA to visualize DNA in living cells directly. Thus, we present the first comprehensive method for live‐cell imaging of cellular and viral nucleic acids using a two‐step labeling approach. [ABSTRACT FROM AUTHOR]

A new class of phosphorus-doped triptycenes was designed and synthesized via a Diels–Alder reaction between alkynylphosphonates and anthracene, followed by oxidative cyclization. The packing interaction and molecular alignment in the single crystals revealed that the weak C–H⋯π (2.825 Å) interaction guides the self-assembly of phosphindole oxide iptycenes. The photophysical and electrochemical properties of these photoluminescent phosphorus-doped iptycenes were characterized to gain a deeper understanding of their fluorescence tunability. The presence of functional groups on the phenyl ring of the P-doped fin and the chemical environment of the P atom both had an effect on the fluorescence emission. [ABSTRACT FROM AUTHOR]

The natural product class of the sorbicillinoids is composed of structurally diverse molecules with many strong, biomedically relevant biological activities. Owing to their complex structures, the synthesis of sorbicillinoids is a challenging task. Here we show the first total synthesis of the fungal sorbicillinoids spirosorbicillinols A–C. The convergent route comprises the chemo-enzymatic transformation of sorbicillin to the highly reactive sorbicillinol and the assembly of scytolide and isomers starting from shikimic and quinic acid analogs. The key step in the total synthesis is the fusion of both building blocks in a Diels-Alder cycloaddition leading to the straightforward formation of the characteristic sorbicillinoid bicyclo[2.2.2]octane backbone. This work provides unifying access to all natural spirosorbicillinols and unnatural diastereomers. Spirosorbicillinols A–C are fungal natural products that display various biological properties, but their total synthesis has yet to be accomplished. Here, the authors report the total synthesis of spirosorbicillinols A–C based on a chemo-enzymatic transformation of sorbicillin into sorbicillinol, which is fused to synthetically prepared scytolide and isomers by a Diels-Alder cycloaddition reaction. [ABSTRACT FROM AUTHOR]

Keywords: Lewis acids; homogeneous catalysis; water-tolerant; kinetic analysis; zirconium; amides; esters; ethers EN Lewis acids homogeneous catalysis water-tolerant kinetic analysis zirconium amides esters ethers 1678 1684 7 08/18/23 20230901 NES 230901 Graph Lewis acidic reagents and catalysts are highly versatile in synthetic chemistry as they promote a wide range of organic reactions. The zirconocene triflate catalyst was assessed in the model reaction using benzoic acid and 2-phenylethanol in an equimolar ratio (0.5 M), which proceeded reliably in aromatic solvents to form the ester product in ca. 70% yield after 24 hours at 80 °C. In addition, up to 50 equivalents of water to catalyst could be added to the reaction mixture without negatively affecting the reaction rate, whereas the addition of molecular sieves reduced the activity of the zirconocene catalyst. Lewis acids, homogeneous catalysis, water-tolerant, kinetic analysis, zirconium, amides, esters, ethers. [Extracted from the article]

Both C60 fullerene and indene were detected in certain astrophysical objects. It is then possible that these two molecules may react together in space forming adducts like indene-C60 mono-adduct (ICMA) as well as the indene-C60 bis-adducts (ICBA). In view of the potential detection of such adducts in space, the chemical thermodynamics of the reaction between C60 and indene was analyzed using the thermochemical group increment approach. ICMA and ICBA were synthesized and their composition and stability was studied with thermogravimetric analysis and derivative thermogravimetry (TGA-DTG). ICBA and moreover ICMA resulted stable and strong adducts. In particular, the latter is stable up to 350 °C and this fact increases the chances to find it in space. Furthermore, the retro Diels-Alder reaction was accurately studied on ICMA with differential scanning calorimetry (DSC) and an unusually high activation energy for the decomposition was determined and explained with the chemical thermodynamic data. The electronic absorption spectra of ICMA and ICBA were studied in n-hexane and the molar extinction coefficients of the main absorption bands have been determined. A possible way to detect such adducts is through electronic absorption spectroscopy, while the infrared spectroscopy of ICMA and ICBA is analyzed and discussed in the following second part of this work. [ABSTRACT FROM AUTHOR]

Methyl pyropheophorbides‐a possessing an o/m‐(methoxycarbonyl)phenyl group at the 3‐position were prepared by Diels–Alder reaction of 3‐(trans‐1,3‐butadienyl)chlorin with methyl propiolate and successive didehydrogenation of the resulting 1,4‐cyclohexadienes. The 3‐arylated chlorin bearing the sterically demanding o‐COOMe group as the major product was a 1:1 mixture of high‐performance liquid chromatography‐separable rotational isomers around the C3–C31 bond, while the minor product with the m‐COOMe was less sterically hindered to exhibit rapid atropisomerization at room temperature. The 3‐aryl group of the major product was nearly perpendicular to the chlorin π‐system and less conjugated with the chlorin moiety than that of the minor product wherein more π‐conjugation occurred to give slightly red‐shifted Qy bands. Although both the atropisomers of the o‐substitute in dichloromethane showed similar visible absorption bands and fluorescence emission data, their circular dichroism bands in the ultraviolet‐C light region were dependent on the stereochemistry. [ABSTRACT FROM AUTHOR]

The Diels–Alder reaction of three chiral dihydro‐2H‐[2,3‐a]oxazolopyridines with N‐methylmaleimide afforded the corresponding chiral cycloadducts as diastereomeric mixtures. In the presence of a solvent, some of the originally formed adducts underwent isomerisation to new isoquinuclidines. [ABSTRACT FROM AUTHOR]

The formal synthesis of (±)‐salvinorin A is presented. Our approach utilizes two distinct gold(I) catalytic processes. The combination of a gold(I)‐catalyzed reaction with an intermolecular Diels–Alder reaction followed by a gold(I)‐catalyzed photoredox reaction generated in eight steps the framework of the natural product with high diastereoselectivity. [ABSTRACT FROM AUTHOR]

Rate constants of the Diels–Alder reaction of 2,5-dimethylfuran (1) with N-phenylmaleimide (2) have been determined in five solvents in the temperature range from 25 to 45°C and pressure range from 1 to 1000 bar. The enthalpies, entropies, Gibbs free energies of activation, and volume parameters of this reaction have been calculated. The equilibrium constants for the reaction of 1 and 2 in benzene have been determined in the temperature range from 25 to 55°C, and the enthalpy and entropy of the reaction have been calculated. [ABSTRACT FROM AUTHOR]

A water‐soluble 1,2,4,5‐tetrazine‐substituted carbon‐dipyrromethene (C–DIPY) was synthesized from the previously reported carbonyl pyrrole dimer through a two‐step procedure. Owing to the presence of a tetrazine moiety, the fluorescence emission of this compound was largely quenched in phosphate‐buffered saline at pH 7.4. Upon addition of a bicyclo[6.1.0]non‐4‐yne (BCN) derivative, the tetrazine‐based quenching component of the compound was disrupted through the inverse electron‐demand Diels‐Alder reaction to restore the fluorescence in up to 6.6‐fold. This bioorthogonal activation was also demonstrated using U‐87 MG human glioblastoma cells, in which the fluorescence intensity of this C–DIPY could be enhanced by 8.7‐fold upon post‐incubation with the BCN derivative. The results showed that this tetrazine‐caged C–DIPY can serve as a bioorthogonally activatable fluorescent probe for bioimaging. The compound, however, was found to reside preferentially in the lysosomes instead of the mitochondria of the cells as predicted based on its cationic character, which could be attributed to its energy‐dependent endocytic cellular uptake pathway, for which lysosomes are the end station. [ABSTRACT FROM AUTHOR]

Isoselenocyanates are valuable coupling partners required for preparing key chemical intermediates and biologically active molecules in an accelerated and effective way. Likewise, (Z)‐2‐oxo‐N‐phenylpropanehydrazonoyl chlorides have been employed in numerous one‐step heteroannulation reactions to assemble the structural core of several various kinds of heterocyclic compounds. Here, we describe the inverse electron demand 1,3‐dipolar cycloaddition reaction of isoselenocyanates with a variety of substituted (Z)‐2‐oxo‐N‐phenylpropanehydrazonoyl chlorides to generate, regioselectively and stereoselectively, a series of 5‐arylimino‐1,3,4‐selenadiazole derivatives comprising a multitude of functional groups on both aryl rings. The synthetic method features gentle room‐temperature conditions, wide substrate scope, and good to high reaction yields. The selenadiazoles were separated by gravity filtration in all instances and chemical structures were validated by multinuclear NMR spectroscopy and high accuracy mass spectral measurements. First conclusive molecular structure elucidation of the observed 5‐arylimino‐selenadiazole regioisomer was verified by single‐crystal X‐ray diffraction analysis. Crystal‐structure measurement was successfully carried out on (Z)‐1‐(4‐(4‐iodophenyl)‐5‐(p‐tolylimino)‐4,5‐dihydro‐1,3,4‐selenadiazol‐2‐yl)ethan‐1‐one and (Z)‐1‐(5‐((4‐methoxyphenyl)imino)‐4‐(4‐(methylthio)phenyl)‐4,5‐dihydro‐1,3,4‐selenadiazol‐2‐yl)ethan‐1‐one. Likewise, the (Z)‐geometry of the hydrazonoyl chloride reactant was proven by X‐ray diffraction studies. As representative examples, crystal‐structure determination was carried out on (Z)‐2‐oxo‐N‐phenylpropanehydrazonoyl chloride and (Z)‐N‐(3,5‐bis(trifluoromethyl)phenyl)‐2‐oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP‐D4/def2‐TZVP level were conducted to support the noted experimental findings and suggested mechanism. [ABSTRACT FROM AUTHOR]

Organic synthesis under green and efficient conditions is crucial for sustainable development. Among the 12 principles of green chemistry, using "safer solvents" is considered as one of the vitally necessary principles of correlated to the organic syntheses. Water is the most abundant and entirely safe molecule in the earth. It is a non-toxic, nonflammable, odorless, colorless, cheapest, renewable, easily accessible, and non-hazardous natural compound. Actually, water is the most ordinary and extraordinary solvent in the world. It is the only compound that naturally exists in three states of matter as solid, liquid, and gas. So, it occupies a unique position in nature due to its task as a solvent for biochemical reactions performed in the bodies of creatures. From the view point of organic synthesis, some of the chemical transformations such as Diels–Alder cycloaddition reaction are found to be more accelerated in water than traditional organic solvents. Ease of product separation is also another advantage of using water in organic reactions, even though, in the reactions that no remarkable rate acceleration is seen. This short review is focused on the importance of the role of water in promoting organic reactions. Organic reactions using water as a green solvent focusing on biphasic systems are reviewed. In this sense, aqueous phase heterogeneous catalysis reactions have a great interest. The advantages and limitations of using water as a green alternative solvent to volatile organic solvents are discussed. We have tried to show a clear image of the role of water in organic reactions. Thus, several considerable examples are given, and some related concepts such as hydrophobic effect, hydrogen bonding, phase-transfer catalysts, and superheated water as essential factors in organic reactions are concisely discussed. [ABSTRACT FROM AUTHOR]

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product‐like guaianolide‐germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels–Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure–activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C‐14′ were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK‐Hep‐1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK‐Hep‐1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK‐Hep‐1), which were 2.7‐, 2.2‐, and 2.8‐fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK‐Hep‐1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide‐germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents. [ABSTRACT FROM AUTHOR]