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We demonstrate that 2‐alkenylarylaldimines and ketimines undergo thermal 6π‐azaelectrocyclization to generate a wide range of azabicyclic o‐quinodimethanes (o‐QDMs). These o‐QDMs exist as a hybrid of a diene and a benzylic diradical. The diradical nature was confirmed by their ability to undergo dimerization and react with H‐atom donor, 2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) and O2. In addition, the interception of the diradicaloid o‐QDMs by H‐atom transfer was used to synthesize five tetrahydroisoquinoline alkaloids and related bioactive molecules. The diene form can undergo [4+2] cycloaddition reactions with different dienophiles to generate bridged azabicycles in high endo:exo selectivity. The azabicyclic o‐QDMs can be generated for [4+2] cycloaddition from a wide range of electronically and sterically varied 2‐alkenylarylimines, including mono, di, tri and tetrasubstituted alkenes, and imines derived from arylamine, alkylamine (1°, 2°, 3°), benzylamine, benzylsulfonamide and Boc‐amine. [ABSTRACT FROM AUTHOR]

A new strategy for N-borylenamines by reaction of 2-alkynyl benzyl azides with B(C6F5)3 was developed. This novel 1,3-carboboration reaction proceeded via a 5-exo-dig cyclization/formal 1,1-carboboration/ B(C6F5)2 shift reaction sequence. Additionally, N-borylenamines can undergo hetero Diels–Alder (HDA) reactions with a variety of dienophiles. Our results are an attractive complement to HDA reactions. [ABSTRACT FROM AUTHOR]

Chiral cyclohexenylallenes are readily accessed from 1‐enynes, aldehydes and chiral secondary amines in good yields (up to 79 % yield) with excellent enantioselectivities (up to 99 % ee), through CuI catalyzed the formation of chiral propargylamine intermediates. Subsequent Yb(OTf)3 catalyzed [4+2] cycloaddition reaction of cyclohexylallenes with the dienophiles tetracyanoethylene and diethyl acetylenedicarboxylate afforded the corresponding bicyclic products in 69–75 % yield and 84–90 % ee. [ABSTRACT FROM AUTHOR]

The rhodium‐catalyzed hydroformylation of alkynyl sulfides at 40 °C under 5 bars of syngas is described. The method gives access to α‐sulfenyl acroleins with α/β regioselectivities up to 89/11 and is applicable to alkyl or aryl substituted substrates. It is effective even on more complex substrates, such as cysteine and cholesterol derivatives. To demonstrate the synthetic potential of the obtained products, (Z)‐3‐cyclohexyl‐2‐methylsulfenyl acrolein was selected as an example and its sulfur atom selectively oxidized to the corresponding sulfoxide or sulfone. Acid‐promoted (Z) to (E) isomerization of the double bond occurred during oxidation. The three obtained sulfenyl‐, sulfinyl‐, and sulfonyl‐functionalized acroleins have been then used as dienophiles to access cyclohexene carbaldehydes. [ABSTRACT FROM AUTHOR]

A tandem aldol condensation/Diels‐Alder sequence of reactions was designed leading to the synthesis of a new series of derivatives of polysubstituted‐decalines. Both steps of the process took place in the same pot and in the presence of H2O/PEG as the medium and diethylamine as the catalyst of the process. The required dienes were formed in situ and reacted with the dienophile (acrylonitrile) to produce high yields of the final decaline derivatives. Mechanistic studies suggested that the process goes through an initial aldol condensation reaction followed by a [4+2] cycloaddition step and then an olefinic bond rearrangement to give the final adducts. To support the proposed mechanism, the intermediate dienes were synthesized separately as well and their stepwise reactions with the dienophile led to the same products. Ten derivatives of the target structure were prepared and then characterized by various spectroscopic methods and X‐ray crystallography analysis. The procedure was also developed to engage some other dienophiles successfully. [ABSTRACT FROM AUTHOR]

This article discusses the use of redox tags in the radical cation Diels-Alder reaction, specifically focusing on the use of enol ethers as dienophiles. The Diels-Alder reaction is commonly used in synthetic organic chemistry to construct six-membered ring systems. The reaction involves the reactivity between a diene and a dienophile, which is controlled by electronic matching. The radical cation Diels-Alder reaction is a third class that allows for the formation of cyclohexene ring systems between electronically mismatched dienes and dienophiles. The authors of this article have developed an electrochemical and TiO2 photochemical radical cation Diels-Alder reaction using enol ethers as dienophiles. The use of redox tags, which function as both electron donors and acceptors, is crucial for controlling the reactivity of the radical cations. The authors have demonstrated the synthetic utility of this reaction and are continuing to explore further applications. [Extracted from the article]

Since the first report that 1,2,4,5‐tetrazines undergo a bioorthogonal reaction with dienophiles in the form of an inverse electron‐demand Diels‐Alder reaction, the demand for high‐yielding synthetic approaches towards them grew steadily. Despite this significant interest, tetrazines were predominantly accessed via the Pinner synthesis or other Pinner‐like reactions, significantly limiting available substrates. In particular, the synthesis of unsymmetrically substituted s‐tetrazines for the selective conjugation to another species presented a major challenge. To tackle these challenges, new and innovative high‐yielding transformations have been developed to widen the scope of accessible symmetric and unsymmetric tetrazines. For instance, Ni(II), Zn(II), and sulphur‐catalysed reactions between two nitriles and hydrazine were developed, which provide access to a wide range of (un‐)symmetric aryl s‐tetrazines. Also, amidines and orthoesters give tetrazines with alkyl substituents, whereas the usage of CH2Cl2 yields valuable H‐monosubstituted tetrazines. Methods using thiocarbohydrazides, terminal fluoroolefins, oxetane esters, or tosyl hydrazones are among the recent additions. Due to the high interest in tetrazine click‐chemistry approaches, some of which reach beyond inverse electron‐demand Diels‐Alder reactions, we expect this overview of synthetic routes to aid the exploration for further applications of tetrazines. Ultimately, we hope to provide a guide for chemists and chemical biologists for accessing functional s‐tetrazines. [ABSTRACT FROM AUTHOR]

Skeletal editing of organophosphines with cleavage of the P–C bond as the key step represents a daunting challenge due to its high dissociation energy. Herein, we report an efficient catalyst-free strategy to cleave P–Ar bonds and insert transformable propionates therein, thus achieving skeletal editing of ortho-chalcone-substituted organophosphines and the ability to generate a range of novel diphenylphosphine-oxide-substituted 2,3-dihydro-1H-indenes with three contiguous stereocenters in a highly diastereoselective fashion. Surprisingly, replacing the propionate with an acetylenedicarboxylate or propiolamide resulted in two further distinct reaction outcomes: Acetylenedicarboxylates served as efficient dienophiles that undergo formal [4 + 2] cycloaddition with ortho-chalcone-substituted organophosphines to afford λ5-phosphinines, while propiolamide affords an uncommon P/N-heterocycle, benzo[c][1,2]azaphosphol-3-one. [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]

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 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]

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]

Bicycloalkadienes are known to engage in homo‐Diels‐Alder reactions with potent dienophiles such as N‐substituted 1,2,4‐triazoline‐3,5‐diones (TAD). We investigated the reaction of N‐methyl TAD (MeTAD) with the three dienes bicyclo[2.2.1]hepta‐2,5‐diene (norbornadiene), bicyclo[2.2.2]octa‐2,5‐diene, and bicyclo[3.2.2]nona‐6,8‐diene experimentally and computationally. Experimentally, the C7 and C8 dienes resulted in the formation of the expected homo‐Diels‐Alder product. However, the C9 diene formed a rearranged adduct that could be explained by the intermediacy of an aziridinium imide intermediate. These findings were supported by computational studies (ωB97X‐D/def2‐SVP{CH2Cl2}) in which not only were the observed products predicted but transition states leading to the products were successfully located. Ultimately, it was determined that subtle differences in transition state structures and energies determine the course of the reaction. [ABSTRACT FROM AUTHOR]

Organocatalytic asymmetric transformation of common aromatic heterocycles via in situ formation of highly reactive dearomatized ortho‐quinodimethane diene species and subsequent [4+2] cycloaddition with suitable dienophiles has become a powerful tool to enter cyclohexane‐fused heterocycles. Most of these reactions were previously applied to benzo‐fused heterocycles or poorly aromatic rings. Herein, we disclose how previously intractable aromatic imidazole rings, equipped with removable methylidene malononitrile activating handle, could be involved as competent cycloaddends with β‐aryl enals in efficient eliminative [4+2] cycloadditions under mild organocatalytic conditions. This method allowed the efficient and direct preparation of scantly represented 6,7‐dihydrobenzo[d]imidazoles with optimal enantio‐ and regioselectivities. Post‐cycloaddition chemical editing provided imidazole‐based ring systems with diverse oxidation state and functional groups. [ABSTRACT FROM AUTHOR]

A solvent‐free reaction between C6‐unsubstituted 5‐aryl‐1,2,4‐triazines and 2‐amino‐4‐aryloxazoles at high temperature was studied. The reaction proceeds via inverse electron demand aza‐Diels‐Alder reaction between the oxazole moiety as dienophile and the 1,2,4‐triazine moiety as diene with the highly regioselective formation of 3,6‐diarylpyridines in up to 60 % isolated yield. The structure of one of the key‐products was proven by the X‐ray diffraction analysis, and the mechanism of the transformation was proposed. The reaction proceeds well for both 6‐aryl and 6‐hetaryl‐1,2,4‐triazines in the presence of the electron acceptor substituent at the position 3. In the case of the donor substituent in position 3, the pyridine yields are significantly reduced. In the case of 5,6‐nonsubstituted 1,2,4‐triazines, the triazine cycle is degraded without product formation. The high regioselectivity of the reaction as well as solvent‐free conditions are valuable advantages of the present synthetic approach. [ABSTRACT FROM AUTHOR]

We have developed a novel system of organic spiro-heterocyclic compounds: like diazaspiro-[5.5] undec-8-ene and oxaspiro [bicyclo [2,2,1 ] heptane-2,1-cyclohexane] dione system with the reaction of Diels-Alder catalyzed with TiCl4 in high regio and stereo-selective way and excellent yield. Initially, we developed different dienophiles and confirmed their structures by spectroscopic methods, ¹H NMR, 13CNMR. then we studied the mechanistic and stereo-chemical action of the various dienophiles concerning the dienes. Finally, the structure of the various newly synthesized products was established by the spectroscopic methods: ¹H-NMR, 13C-NMR, the stereochemical aspects of the Diels-Alder reaction, and cycloaddition [4 + 2] were established, and the reaction conditions were mentioned. [ABSTRACT FROM AUTHOR]

A one-pot synthesis of 2H-thiopyrans from β-amino enones has been developed. Sequential treatment of β-amino enones with the Lawesson's reagent and electron-deficient dienophiles (maleic anhydride and maleimides) in dichloromethane gave 2H-thiopyran derivatives in 25—62% yields. [ABSTRACT FROM AUTHOR]

Spatiotemporally functionalized hydrogels have exciting applications in tissue engineering, but their preparation often relies on radical‐based strategies that can be deleterious in biological settings. Herein, the computationally guided design, synthesis, and application of a water‐soluble cyclopentadienone‐norbornadiene (CPD‐NBD) adduct is disclosed as a diene photocage for radical‐free Diels‐Alder photopatterning. We show that this scalable CPD‐NBD derivative is readily incorporated into hydrogel formulations, providing gels that can be patterned with dienophiles upon 365 nm uncaging of cyclopentadiene. Patterning is first visualized through conjugation of cyanine dyes, then biological utility is highlighted by patterning peptides to direct cellular adhesion. Finally, the ease of use and versatility of this CPD‐NBD derivative is demonstrated by direct incorporation into a commercial 3D printing resin to enable the photopatterning of structurally complex, printed hydrogels. [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]

In the chalcogen series, tellurium species exhibit the strongest chalcogen bonding (ChB) interaction with electron‐rich atom. This property explains the renewed interested toward tellurium‐based derivatives and their use in different applications, such as organocatalysis. In this context, the catalytic activity of telluronium salts in the Povarov reaction is presented herein. Different dienophiles, as well as imines of variable electronic nature, efficiently react in the presence of catalytic amount of either diarylmethyltelluronium or triaryltelluronium salts. Both catalysts could also readily perform the three‐component Povarov reaction starting from aldehyde, aniline and dihydrofuran. The reactivity of telluroniums towards imines and aldehydes was confirmed in the solid state by the ability of Te atom to interact through ChB with the oxygen carbonyl of acetone, and in solution with significant shift variations of the imine proton and of the tellurium atom in 1H and 125Te NMR spectroscopy. For the most active telluronium catalysts bearing CF3 groups, association constants (K) with N‐phenyl phenylmethanimine in the range 22–38 M−1 were measured in dichloromethane. [ABSTRACT FROM AUTHOR]

The reactions of 5-(1,2-dicarbadodecaboran-1-yl)-3-(2-pyridyl)-1,2,4-triazines with various dienophiles (2,5-norbornadiene, 1-morpholinocyclopentene, 1,2-dehydrobenzene, and 2-amino-4-phenyloxazole) were studied. It was shown that the presence of a carborane fragment in the 1,2,4-triazine ring causes an atypical reaction with dienophiles without the formation of the expected aza-Diels–Alder reaction products except for the reaction with 2,5-norbornadiene. The reaction of 5-(1,2-dicarbadodecaboran-1-yl)-3-(2-pyridyl)-1,2,4-triazines with 2-amino-4-phenyloxazole unexpectedly led to the formation of the corresponding 4,5-dihydro-1,2,4-triazines. One of the previously described procedures for the direct introduction of a carborane residue into the C5 position of 1,2,4-triazines was optimized. [ABSTRACT FROM AUTHOR]

A series of Diels–Alder reactions between the diene 2,2'‐biaceanthrylene and several dienophiles is presented. The diene is a cyclopenta‐fused polycyclic aromatic hydrocarbon with anthracene units linked by two cyclopentene rings. Depending on the dienophile, the major product was the result of a single addition (dimethyl acetylenedicarboxylate) or double addition (quinone, benzyne) to the diene. Single crystal X‐ray analysis of the quinone‐derivative shows a propeller‐like structure composed of mixed enantiomers. The synthesis and photophysical properties of these compounds are presented. [ABSTRACT FROM AUTHOR]

The Diels–Alder (DA) reaction is a promising tool for obtaining covalently crosslinked hydrogels due to its reaction bioorthogonality, the absence of by-products, and the application of mild conditions without a catalyst. The resulting hydrogels are in demand for use in various fields of materials science and biomedicine. While the dynamic nature of the cycloaddition of diene and dienophile has previously been used extensively for the fabrication of self-healing materials, it has only recently spread to the expansion of the functional properties of polymer gels for bioapplications. This review describes strategies and recent examples of obtaining hydrogels based on the DA reaction, demonstrating that the emerging functional properties go beyond self-healing. The types of classifications of hydrogels are listed, depending on the type of reaction and the nature of the components. Examples of obtaining hydrogels based on the normal and inverse electron-demand DA reaction, as well as the application of hydrogels for cell culture, drug delivery, injectable gels, and wound dressings, are considered. In conclusion, possible developmental directions are discussed, including the use of diene–dienophile pairs with a low temperature for the reversal of DA reaction, the modification of nanoparticles by diene and/or dienophile fragments, and new applications such as ink for 3D printing, sensing hydrogels, etc. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chiral heteroatom‐containing bicyclic scaffolds are important pharmacophores and prevalent in bioactive natural products and drug molecules. Herein, we report a unified approach for the divergent synthesis of chiral heteroatom‐containing bicyclic derivatives by lanthanide (III)‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder reactions of 2‐pyrones. These reactions occur with various readily available dihydropyrroles and dihydrofurans as dienophiles, providing a step‐economical synthetic platform for densely functionalized cis‐hydroindoles and cis‐hydrobenzofurans with excellent yields and enantioselectivities. The synthetic utility of this approach is demonstrated by the concise synthesis of (–)‐α‐lycorane and (–)‐lycorine alkaloids. [ABSTRACT FROM AUTHOR]

Diels–Alder reactions of unactivated dienes with various dienophiles were investigated under continuous‐flow conditions. H‐beta zeolite was found to be a suitable catalyst for this type of transformation, allowing a good productivity of 1.88 kg/dm3⋅day space‐time yield and exhibiting excellent catalyst durability over >72 h of continuous operation. The catalyst was easily recyclable up to four times by simple calcination, without loss of activity. [ABSTRACT FROM AUTHOR]

Chiral bis‐oxalamide (CBOA)/rare‐earth metal complexes‐catalyzed asymmetric inverse‐electron‐demand oxa‐hetero‐Diels‐Alder (HDA) reactions were investigated under mild reaction conditions, which was performed between β,γ‐unsaturated α‐ketoesters and various electron‐riched dienophiles, such as cyclopentadiene, 2,3‐dihydrofuran, 3,4‐dihydro‐2H‐pyran, tetrahydropyridine as well as phenyl(vinyl)sulfane. Several series of optically active functionalized 3,4‐dihydro‐2H‐pyran or ring fused dihydropyran derivatives were obtained in high yields with high diastereo‐ and enantioselectivity. The procedure was able to tolerate a relatively wide range of substrates. The coordination mode of chiral bis‐oxalamide with Sc(III) was demonstrated by the X‐ray crystallographic structure, and DFT calculations were carried out to uncover the regio‐ and stereocontrol. [ABSTRACT FROM AUTHOR]

The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to the high nucleophilicity of guanidines, an aza-Michael reaction with dienophiles is more common and presents a huge obstacle in achieving the desired synthetic goal. Our preliminary investigations indicated that the proton could act as a suitable protecting group to regulate the directionality of the reaction. To investigate the role of the protonation state and type of anion, the reactivity of furfuryl guanidines with dimethyl acetylenedicarboxylate was explored. Furfuryl guanidines showed a strong reaction dependence on the nucleophilicity of the counterion and the structure of guanidine. While the reaction of DMAD with the guanidinium halides provided products of an aza-Michael addition, Diels–Alder cycloaddition occurred if non-nucleophilic hexafluorophosphate salts were used. Depending on the structure and the reaction conditions, oxanorbornadiene products underwent subsequent intramolecular cyclization. A tendency toward intramolecular cyclization was interpreted in terms of the pKa of different positions of the guanidine functionality in oxanorbornadienes. New polycyclic guanidines had a slightly decreased pKa in acetonitrile and well-defined geometry suitable for the buildup of selective sensors. [ABSTRACT FROM AUTHOR]

The Diels‐Alder reaction is a very interesting process that has been deeply studied in its achiral version. More recently, in its chiral version, it has also been the focus of many experimental and theoretical reports. Here, we study the Diels‐Alder reaction of 2′‐hydroxychalcones, as dienophiles, with two dienes, catalyzed by chiral organo‐boron Lewis acid complexes. We theoretically evaluate the mechanism that has been empirically proposed in the literature, and we clarify several results that didn't allow the full rationalization of the experimental data. Therefore, we show that similar ligands in the complexes lead to quite different enantioselectivities, due to different steric interactions with the attacking diene. In addition, we also conclude that the low endo/exo selectivities result from two opposite effects in the Diels‐Alder transition states of the endo pathways, which substantially increase their activation energy, reaching values very similar to those calculated for the exo transition state structures. [ABSTRACT FROM AUTHOR]

The synthesis and reactivity in an [4+2] inverse electron demand hetero Diels‐Alder reaction (ihDA) of an original class of electron‐poor heterodienes, the N‐substituted‐1H‐benzo[c][1,2]thiazin‐4‐one‐2,2‐dioxides, are described. These are highly reactive electrophiles that allow easy access to unprecedented benzo‐thiazine glyco‐fused derivatives in a remarkably selective way, even when using acetylated glycals, previously unexplored within this version of ihDA. DFT calculations support the experimental data, and moreover show that acetylated dienophiles can easily react making cycloadditions feasible. [ABSTRACT FROM AUTHOR]

The value of covalent post‐synthetic modification in expanding the chemistry and pore versatility of reticular solids is well documented. Here we use mesoporous crystals of the metal–organic framework (MOF) UiO‐68‐TZDC to demonstrate the value of tetrazine connectors for all‐purpose inverse electron‐demand Diels–Alder ligation chemistry. Our results suggest a positive effect of tetrazine reticulation over its reactivity for quantitative one‐step functionalization with a broad scope of alkene or alkyne dienophiles into pyridazine and dihydropyridazine frameworks. This permits generating multiple pore environments with diverse chemical functionalities and the expected accessible porosities, that is also extended to the synthesis of crystalline fulleretic materials by covalent conjugation of fullerene molecules. [ABSTRACT FROM AUTHOR]

Diene‐transmissive hetero‐Diels–Alder sequences involving carbonyl dienophiles are reported for the first time. High enantioselectivities are achieved in the reaction of phenylglyoxal with a broad range of dendralene structures, through the optimization of a Pd2+ catalyst system. The initial catalyst‐controlled enantioselective oxa‐Diels–Alder (ODA) cycloaddition to a [3]dendralene generates a dihydropyran carrying a semicyclic diene. This participates in a subsequent catalyst or substrate‐controlled Diels–Alder reaction to generate sp3‐rich fused polycyclic systems containing both heterocycles and carbocycles. Computational investigations reveal a concerted asynchronous mechanism. π‐Complexation of a diene C=C bond to Pd2+ occurs in both the pre‐transition state (TS) complex and in cycloaddition TSs, controlling stereoselectivity. A formal enantioselective [4+2]cycloaddition of a CO2 dienophile is demonstrated. [ABSTRACT FROM AUTHOR]

The 2(H)-pyran-2-one bearing electron-donating tert-butylcarbamate (BocNH-) group at the 5- position is a "chameleon" diene and undergoes efficient Diels–Alder cycloadditions with alkene dienophiles with both electron-rich and electron-deficient substituents. Cycloadditions afford the 5-substituted bicyclic lactone cycloadducts regardless of the electronic nature of the dienophile. However, cycloadditions with electronically matched electron-deficient dienophiles proceed faster than those with electronically mismatched electron-rich dienophiles. [ABSTRACT FROM AUTHOR]

In the search for new intermediates for heterocyclic synthesis, the reactivity of 6‐iminophosphoranepyrimidines against dimethyl acetylenedicarboxylate (DMAD) and ethyl propiolate as dienophiles, was studied in this work. The presence of a viable 2‐azadienic moiety in pyrimidin‐4‐one rings (oxo derivatives) favored reaction of DMAD by [4 + 2]/retro‐[4 + 2] sequence, in addition to the expected [2 + 2] cycloaddition/retrocycloaddition involving phosphazene moiety. In contrast, pyrimidine derivatives lacking a viable 2‐azadienic residue reacted only through phosphazene group by the aforementioned [2 + 2]/retro‐[2 + 2] tandem process. Ethyl propiolate (non‐symmetric dienophile) proved less reactive in the study, giving rise to undesired side reactions. [ABSTRACT FROM AUTHOR]

Mulberry Diels–Alder-type adducts (MDAAs) are unique phenolic natural products biosynthetically derived from the intermolecular [4 + 2]-cycloaddition of dienophiles (mainly chalcones) and dehydroprenylphenol dienes, which are exclusively distributed in moraceous plants. A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980. Structurally, the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups (Types A − H), while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs (Type I). These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures, remarkable biological activities, and synthetic challenges. The present review provides a comprehensive summary of the structural properties, bioactivities, and syntheses of MDAAs. Cited references were collected between 1980 and 2021 from the SciFinder, Web of Science, and China National Knowledge Internet (CNKI). [ABSTRACT FROM AUTHOR]

4-Acyl-1H-pyrrole-2,3-diones fused at [e]-side with a heterocyclic moiety are suitable platforms for the development of a hetero-Diels–Alder-reaction-based, diversity-oriented approaches to series of skeletally diverse heterocycles. These platforms are known to react as oxa-dienes with dienophiles to form angular 6/6/5/6-tetracyclic alkaloid-like heterocycles and are also prone to decarbonylation at high temperatures resulting in generation of acyl(imidoyl)ketenes, bidentate aza- and oxa-dienes, which can react with dienophiles to form skeletally diverse products (angular tricyclic products or heterocyclic ensembles). Based on these features, we have developed an approach to two series of skeletally diverse 4H-1,3-oxazines (tetracyclic alkaloid-like 4H-1,3-oxazines and 5-heteryl-4H-1,3-oxazines) via a hetero-Diels–Alder reaction of 4-acyl-1H-pyrrole-2,3-diones fused at [e]-side with cyanamides. The products of these transformations are of interest for drug discovery, since compounds bearing 4H-1,3-oxazine moiety are extensively studied for inhibitory activities against anticancer targets. [ABSTRACT FROM AUTHOR]

Activated acetylenic substrates such as acetylenic esters and alkyl propiolates are very important in organic synthesis. Due to their electron deficiency, these compounds are widely used in combinatorial and multicomponent reactions, enabling the synthesis of a large variety of novel compounds. In addition, these substrates are powerful Michael acceptors and convenient dienophiles and dipolarophiles in Diels–Alder and 1,3-dipolar cycloaddition reactions. The addition of different nucleophiles, primarily phosphorus, nitrogen or sulfur, to the triple bonds of these substrates produces key intermediates, such as Tebby and Huisgen zwitterions, which can lead to designing pathways toward the generation of spirocyclic and polycyclic compounds. This account highlights recent studies on the chemistry of acetylenic esters and their applications in organic synthesis. 1 Introduction 2 Synthesis of Acyclic and Monocyclic Compounds 3 Synthesis of Spirocyclic Compounds 4 Synthesis of Polycyclic Compounds 5 Conclusion [ABSTRACT FROM AUTHOR]

Rosenthal's‐reagent‐mediated intramolecular cyclometallation of α,α‐dialkynyldipyrrin nickel(II) complex and subsequent acid treatment afforded a 1,3‐butadiene‐embedded porphyrin(2.1.2.1), 6, which served as a reactive diene towards dienophiles such as dimethyl acetylenedicarboxylate (DMAD) and benzyne to give corresponding Diels–Alder adducts. Diels–Alder reaction of 6 and benzdiyne gave adducts 14, 15 a, and 15 b along with a trace amount of porphyrin(2.1.2.1) barrel 13. Stepwise routes using 14 or 15 a/15 b as a substrate allowed for the synthesis of 13 as a single stereoisomer. The nanobarrel structure for 13 was revealed by X‐ray diffraction, where its cavity held two chloroform molecules via C−H⋅⋅⋅π interaction. DFT calculations revealed that the electrostatic attraction was dominant with binding energy of 32.8 kcal mol−1. [ABSTRACT FROM AUTHOR]

A straight forward synthetic protocol for spiro and fused chromenes has been developed by base promoted oxa -Michael/Mannich reaction of salicyl N -tosylimines and various cyclic dienophiles. 1,4-diazabicyclo[2.2.2]octane (DABCO) promoted [4 + 2] cycloaddition reaction of salicyl N -tosylimines and 3-methyleneoxindoles or 2-arylidene-1,3-indanediones in THF at room temperature afforded functionalized spiro[chromane-3,3′-indolines] or spiro[ chromane -3,2′- inden ]-1′,3′-diones in moderate to good yields and with high diastereoselectivity. On the other hands, the similar [4 + 2] cycloaddition of salicyl N -tosylimines and 5,6-unsubstituted 1,4-dihydropyridines resulted in tetrahydrochromeno[3,2- b ]pyridine derivatives in satisfactory yields. [Display omitted] [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]

For a long time, allenes—and cumulenic systems in general—played a relatively minor role in Diels–Alder cycloadditions. This situation has changed, since allenes are more readily available and as their unique stereochemical features in [4+2]cycloadditions are more widely recognized. This review presents a comprehensive overview of allenes in Diels–Alder processes using selected examples. Allenes in dienes, dienophiles and cycloadducts are covered, inter- and intramolecular Diels–Alder cycloadditions are discussed, and stereochemical features of the addition process are described. Areas of emerging importance are also covered, including allenic components in dehydro-Diels–Alder processes, and dendralenic allenes in Diels–Alder sequences for the rapid generation of target-relevant molecular complexity. Preparatively useful methods for allenic precursor synthesis are also discussed. 1 Introduction 2 Allenic Dienes 2.1 Vinylallenes 2.2 Bisallenes 2.3 Cross-conjugated Allenes 3 Allenic Dienophiles 4 Intramolecular Diels–Alder Cycloadditions 5 Allenic Cycloadducts 6 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

This comprehensive review summarizes the published literature data concerning the intramolecular Diels–Alder reactions of vinylarenes (the IMDAV reaction) and alkynyl arenes from 1970 to 2019, and covers mainly intramolecular [4+2] cycloaddition reactions of vinyl- or acetylene-substituted furans, thiophenes, pyrroles, indoles, imidazoles, benzenes, and naphthalenes, in which the unsaturated substituent is linked directly to an arene moiety. The selected area of the Diels–Alder reaction differs from other forms of [4+2] cycloadditions due to the uniqueness of the diene fragment, which, along with an exocyclic multiple bond, includes the double bond of an aromatic or heteroaromatic nucleus in its system. Thus, during the formation of the [4+2] cycloaddition intermediate, the aromaticity of furan, thiophene and even benzene rings is broken, leading, as a rule, to the formation of heterocyclic structures rarely accessible by other methods, in contrast to the majority of intermolecular Diels–Alder reactions, with the highest degree of chemo-, regio-, and diastereoselectivity. Therefore, the IMDAV approach is often used for the synthesis of naturally occurring and bioactive molecules, which are also discussed in this review alongside other applications of this reaction. Whenever possible, we have tried to avoid examples of radical, photochemical, oxidative, precious-metal-complex-catalyzed cyclizations and other types of formal [4+2] cycloadditions, focusing on thermal Diels–Alder reactions in the first step, according to the classical mechanism. The second stage of the process, aromatization, is unique for many initial substrates, and hence considerable attention in this overview is given to the detailed description of the reaction mechanisms. 1 Introduction 2 IMDAV Reactions of Vinylfurans 2.1 Alkenes as Internal Dienophiles 2.2 Alkynes and Allenes as Internal Dienophiles 3 IMDAV Reactions of Vinylthiophenes 3.1 Alkenes as Internal Dienophiles 3.2 Alkynes as Internal Dienophiles 4 IMDAV Reactions of Vinylbenzothiophenes 5 IMDAV Reactions of Vinylpyrroles 6 IMDAV Reactions of Vinylindoles 6.1 Alkenes as Internal Dienophiles 6.2 Alkynes as Internal Dienophiles 7 IMDAV Reactions of Styrenes and Vinylnaphthalenes 7.1 Alkenes as Internal Dienophiles 7.2 Alkynes as Internal Dienophiles 7.3 Alkynes as Internal Dienophiles in Aryl Acetylenes (the Intramolecular Dehydro Diels–Alder Reaction) 8 IMDAV Reactions of Vinylimidazoles, Vinylisoxazoles and Vinylpyridines 9 Conclusion 10 Abbreviations [ABSTRACT FROM AUTHOR]

The oxa-Diels–Alder reaction is a straightforward, atom-economical process for the construction of six-membered oxacycles, which are privileged structures due to their very common occurrence in several pharmaceuticals and natural products. As with many other asymmetric transformations, organocatalysis provides an elegant pathway to their synthesis via [4+2] annulation under mild reaction conditions. The oxa-Diels–Alder reaction utilizes either an α,β-unsaturated carbonyl as an oxa-diene with a suitable dienophile or a simple carbonyl as a dienophile with other dienes. A range of organocatalysts has been explored in the past decade to execute this strategy. The catalysts induce stereoselectivities via two basic reactivities: (1) The formation of chiral intermediates, or (2) selectively activating suitable reactants via a transition state. The present short review compiles organocatalyzed asymmetric oxa-Diels–Alder reactions published over the last ten years, along with detailed discussions on mechanistic approaches. 1 Introduction 2 Catalysis through Covalent Activation 2.1 N -Heterocyclic Carbenes 2.2 Amines 2.3 Isothiourea Catalysis 2.4 Phosphines 3 Catalysis through Non-Covalent Activation 3.1 Bifunctional Amines 3.2 Brønsted Acids 3.3 Guanidines 4 Multicatalysis through Both Covalent and Non-Covalent Activation 5 Conclusion [ABSTRACT FROM AUTHOR]

The cyclohexene motif is ubiquitous in nature and specialty chemicals. A straightforward selective access to chiral cyclohexenes from unactivated dienes and dienophiles is not feasible by classical Diels–Alder reaction and constitutes an unsolved synthetic challenge. We report a mild and enantioselective iron‐catalyzed cross‐[4+2]‐cycloaddition of unactivated dienes providing access to chiral 1,3‐substituted vinyl‐cyclohexenes. The development of bis‐dihydroisoquinoline ligands was vital to obtain iron complexes that display high reactivities and excellent chemo‐, regio‐ and enantioselectivities towards the targeted cyclohexenes. A range of diene substrates is well accommodated including feedstocks like butadiene, isoprene and myrcene. The structures of different iron complexes are mapped by X‐ray crystallographic analysis and linked to their performance. [ABSTRACT FROM AUTHOR]

A series of naphthalimide – tetrazines were developed as bioorthogonal fluorogenic probes, which could produce significant fluorescence enhancement, notable aggregation-induced emission (AIE) characters and multicolor emissions after bioorthogonal reaction with strained dienophiles. Manipulating the π-bridge in the fluorophore skeleton allows fine-tuning of the emission wavelength and influences the AIE-active properties. With these probes, we succeeded in no-wash fluorogenic protein labeling and mitochondria-selective bioorthogonal imaging in live cells. [ABSTRACT FROM AUTHOR]

Herein, starch-cellulose interpenetrating network (IPN) hydrogels were fabricated by sequential Diels-Alder click reaction and photopolymerization in water. Moreover, β-cyclodextrin, a commonly used host molecule in supramolecular chemistry, was also introduced to improve the performance of the IPN hydrogel. Firstly, the starch-based dienes were synthesized by modifying starch with N-maleoyl-β-alanine, and the cellulose-based dienophiles were obtained by the reaction of cellulose and furfurylamide succinate; Secondly, the as-synthesized starch-based dienes, cellulose-based dienophiles, polymerizable β-cyclodextrin, crosslinker, and acrylamide were dissolved in water and obtained a transparent solution. The solution was maintained in a water bath of 50 °C for 3 h, forming the first network via catalyst-free click Diels-Alder reaction, subsequently, the second network was formed by photopolymerization. Their preparation conditions were optimized via one-factor experiments and their properties and structures were characterized. Finally, 5- fluorouracil (5-Fu) was used as a model drug to study the sustained release behavior of the drug-loaded hydrogels. Release profile was found to fit in Ritger-Peppas kinetic model and polymer relaxation and drug diffusion made a valuable contribution to drug release. Taking into account the virtues of easily controllable photopolymerization and catalyst-free Diels-Alder reaction, the strategy described here has a potential application in the preparation of IPN hydrogels. • Starch-cellulose IPN hydrogels were prepared via DA reaction and photopolymerization. • The reaction can carry out conveniently in water with rapid speed. • The IPN hydrogels has certain biocompatibility and could slow the release of 5-Fu. • Release profile was found to fit in Ritger-Peppas kinetic model. [ABSTRACT FROM AUTHOR]

The present paper gives an account of research in different areas of organic chemistry carried out at the University of Botswana. It describes the results of phytochemical investigations carried out on eight species of genus Erythrina. Several new alkaloids and non-alkaloids have been isolated and screened for different biological activities. Physicochemical properties and fatty acids composition of some oils are described as well. The paper also documents some synthetic approaches to natural products and their derivatives, ß-amino acids, ß-lactams, 1,3,4-oxadiazolines, spirooxindole-2-azetidinones and spirooxindole-oxiranes. The synthetic approaches include the elaboration of the Diels-Alder product of furan and some dienophiles to give the natural product oryzoxymycin and cyclohexyl-ß-amino acids. In addition, studies on synthesis of chromane/chromene ring systems are summarized. The application of a-diazoketones and ethyl diazoacetate in the synthesis of ß-lactams, 1,3,4-oxadiazoline, spirooxindole-2-azetidinones, and spirooxindole-oxiranes is described. Some oxidative, reductive, and other reactions of ß-lactams are discussed. In the green chemistry domain, results on grinding-induced synthesis of benzoxazines and microwave-assisted synthesis of benzil diimines are presented. Bis(acetylacetonato)copper(II)-catalyzed oxidation reactions of hydrazones and the sec-alcoholic group of benzoins to azines and 1,2-diketones, respectively, are described. In addition, the PdCl2-catalyzed transfer hydrogenation of alkenes to alkanes in the presence Zn powder is accounted. [ABSTRACT FROM AUTHOR]

This work reports new studies of the activity and Diels–Alder kinetics of a series of dienophiles: tetracyanoethylene (1), 2,3‐dicyano‐p‐benzoquinone (10), and N‐phenylimide‐1,4‐benzoquinone‐2,3‐dicarboxylic acid (11). Rate differences are interpreted in terms of the donor–acceptor properties of the reagents. The relative π‐acceptor properties of the dienophiles are probed by measuring their interaction energies with a series π‐donor solvents: benzene, toluene, o‐xylene, and chlorobenzene. The normalized interaction energies of 1, 10, and 11 are found to be 100:64:28. Despite the increased energy of the donor–acceptor interaction, dienophile 10 is 255 times less active in the reaction with 9,10‐dimethylanthracene than 11. It is suggested that this is due to the significantly lower energy of π‐bond cleavage in bicyclic dienophile 11, compared with monocyclic 10. [ABSTRACT FROM AUTHOR]

The synthesis and reactivity patterns of the strained dithiete ring are compared with their dimeric tetrathiocin counterparts and higher oligomers, highlighting: (i) their cycloaddition chemistry with organic dienophiles as a route to sulfur-containing heterocycles; (ii) their oxidative addition chemistry to low valent transition metal complexes to generate transition metal dithiolate complexes and; (iii) the base-catalysed isomerizations between different dithiete oligomers. [ABSTRACT FROM AUTHOR]

The Diels–Alder (DA) reaction is regarded as quite a useful strategy in organic and macromolecular syntheses. The reversibility of this reaction and the advent of self-repair technology, as well as other applications in controlled macromolecular architectures and crosslinking, have strongly boosted the research activity, which is still attracting a huge interest in both academic and industrial research. The DA reaction is a simple and scalable toolbox. Though it is well-established that furan/maleimide is the most studied diene/dienophile couple, this perspective article reports strategies using other reversible systems with deeper features on other types of diene/dienophile pairs being either petro-sourced (cyclopentadiene, anthracene) or bio-sourced (muconic and sorbic acids, myrcene and farnesene derivatives, eugenol, cardanol). This review is composed of four sections. The first one briefly recalls the background on the DA reactions involving cyclodimerizations, dienes, and dienophiles, parameters affecting the reaction, while the second part deals with the furan/maleimide reaction. The third one deals with petro-sourced and bio-sourced (or products becoming bio-sourced) reactants involved in DA reactions are also listed and discussed. Finally, the authors' opinion is given on the potential future of the crosslinking–decrosslinking reaction, especially regarding the process (e.g., key temperatures of decrosslinking) or possibly monocomponents. It presents both fundamental and applied research on the DA reaction and its applications. [ABSTRACT FROM AUTHOR]

Mechanisms of the Diels‐Alder (D‐A) reactions between N‐alkyl and aryl‐1,2‐dihydropyridines and dienophiles have been investigated by M06‐2X‐D3/6‐31 + G(d,p) basis set, and SMD model was employed to simulate the solvent effect. The computational results show that the productive process of endo‐product is favorable with lower energy barrier. The calculations of substituent effect indicate that there are some relations between the energy barrier and the productivity. The lower energy barrier means the higher productivity, and the barrier of retro D‐A reaction could also have influence on the productivity. Finally, natural bond orbital Fukui function (NOFF) and frontier molecular orbital theory (FMOT) are employed to analyze the structures and reveal the substances of D‐A reactions. [ABSTRACT FROM AUTHOR]