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Comprehensive Summary: Maleimide derivatives are well‐established reactive intermediates also found in natural products, synthetic pharmaceuticals and functional polymers. Their specific reactivity found widespread applications in the field of bioconjugation and allowed for the development of highly selective functionalizations based on simple additions and cycloadditions with the possible control of central and C–N axial chirality. These multisite‐reactive scaffolds have aroused a long‐standing interest throughout the scientific community more particularly as powerful electrophilic partners and more recently as nucleophilic partners in some specific transformations. The persistent interest in these easily accessible synthetic platforms over the last decade has enabled the development of new enantioselective transformations and the major advancements in this field are presented in this review. Key Scientists: [ABSTRACT FROM AUTHOR]

Alkynylallenes offer the varied reactivity patterns of two different multiple bond linkages either separately or in concert. Initially, a short overview of their syntheses, structures, rearrangement mechanisms and synthetic utility, especially when treated with transition metal reagents such as gold(I), silver(I), platinum metals or metal carbonyls, is presented. Subsequently, we focus on the particular case of 1,2-dien-5-ynes (propargylallenes), whereby the shortness of the single atom bridge, and the consequent proximity of the allenyl and alkynyl moieties, facilitates metal-mediated interactions between them. It is shown how these metals can coordinate to either the alkyne or the allene fragment, thus leading to different cyclisation or rearrangement products, dependent also on whether it is the proximal or the distal double bond of the allene that participates in the reaction. Dimerisation of bromo-substituted fluorenylideneallenes bearing silyl or ferrocenyl substituents can occur in either head-to-head or head-to-tail fashion, thereby yielding propargylallene derivatives that undergo unexpected and novel rearrangements, including the formation of molecules possessing unusually long carbon–carbon single bonds. Fluorenyl-bearing propargylallenes react with silver nitrate or iron carbonyl to form novel organic polycyclic systems. Finally, suggestions are offered for future advances in the area. [ABSTRACT FROM AUTHOR]

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)‐rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza‐BCHs) by an enantioselective zinc‐catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2‐acyl imidazole group and a diverse array of alkynyl‐ and aryl‐substituted imines. The target aza‐BCHs, which consist of α‐chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94 % and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring‐opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid‐catalyzed cycloadditions of BCBs. [ABSTRACT FROM AUTHOR]

A mechanochemical‐enabled Ru‐catalyzed regioselective synthesis of 3,4‐isoxazoles and 3,4,5‐isoxazoles from terminal and internal alkynes and hydroxyimidoyl chlorides is reported. This solid‐state and solvent‐free approach carefully examines the impact of the milling conditions on regiocontrol in 1,3‐dipolar cycloadditions using mechanochemical means. The study reveals that milling frequency, jar material, and the choice of liquid additive for liquid‐assisted grinding (LAG) significantly influence the catalytic activity of the Ru catalyst. Transmission electron microscope (TEM) analysis confirms the crucial role of coordinating liquid additives such as acetone and cyclopentyl methyl ether (CPME) in stabilizing and reducing the size of the in‐situ formed Ru nanoparticles, which is essential for catalytic activity. The applicability of this protocol is further demonstrated through the synthesis of a library of 3,4‐ and 3,4,5‐isoxazoles from a wide range of terminal and internal alkynes with varying physical states and electronic properties that highlights the potential of this method for the synthesis of more complex target molecules. [ABSTRACT FROM AUTHOR]

Allenoates are versatile reagents that can be used for numerous (formal) cycloaddition reactions under (chiral) Lewis base catalysis. Most commonly, the catalysts of choice are phosphines, amines, and N-heterocyclic carbenes. We have recently established the use of readily available chiral isochalcogenoureas as catalysts for asymmetric (4 + 2)-heterocycloadditions of allenoates with various vinylogous acceptors. This represents a complementary approach for allenoate activation and gives access to various highly functionalized chiral dihydropyrans with good to excellent enantioselectivities and diastereoselectivities. [ABSTRACT FROM AUTHOR]

Unexpectedly facile dearomative intramolecular (4+3) cycloadditions of thiophenes with epoxy enolsilanes, providing sulfur‐bridged cycloadducts, are reported. A total of fifteen thiophene substrates have been found to undergo (4+3) cycloaddition smoothly to produce endo and exo (4+3) adducts in yields of up to 83 % with moderate to good diastereoselectivity. Complete conservation of enantiomeric purity was observed when the optically enriched epoxide was used. The desulfurizing transformations of the sulfur‐bridged skeleton of the cycloadducts provide functionalized 6,7‐fused bicyclic frameworks consisting of 1,3‐cycloheptadiene subunits. Density functional theory calculations reveal the origins of the facile dearomatization of thiophenes in these (4+3) cycloadditions. [ABSTRACT FROM AUTHOR]

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A. These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis. [ABSTRACT FROM AUTHOR]

On May 1, 1965, Roald Hoffmann and R. B. Woodward published their second joint communication, Selection Rules for Concerted Cycloaddition Reactions, in the Journal of the American Chemical Society. Herein is presented a historical analysis of Woodward and Hoffmann's determination of the mechanism of cycloadditions. This analysis is based on thorough analyses with Roald Hoffmann of his 1964 and 1965 laboratory notebooks and his archived documents and on numerous in‐person, video, and email interviews. This historical research pinpoints several seminal moments in chemistry and in the professional career of Hoffmann. For example, now documented is the fact that Woodward and Hoffmann had no anticipation that their collaboration would continue after the publication of their first 1965 communication on electrocyclizations. Also pinpointed is the moment in Hoffmann's professional and intellectual trajectories that he became a full‐fledged, equal collaborator with Woodward and Hoffmann's transition from a "calculator" to an "explainer." [ABSTRACT FROM AUTHOR]

Triquinane natural products are an interesting class of polycyclic frameworks that have attracted considerable interest because of their distinct structures and diverse array of biological applications such as antibacterial, antifungal, and anticancer properties and biological diversity of these scaffolds make them promising candidates for drug discovery and medicinal chemistry. These frameworks have a central structure of bicyclo[2.2.1]heptane ring which is linked to another cycloalkane ring generating the a unique tricyclic arrangement. The design and synthesis of triquinane framework is very challenging because of their intricate three-dimensional structure and the requirement for accurate organization of numerous stereocenters. Based on thorough review of literature, cycloadditions and metathesis play a pivotal role for constructing these exciting class of complex frameworks in an efficient and selective manner. In this review we focused mainly on how cycloadditions and metathesis strategies are significant in total synthesis of these interesting class of scaffolds. Here, we summarized the synthetic strategies of linear, angular, and propellane types of triquinane natural products via different cycloaddition protocols as well as photothermal and olefin metathesis which are used as key steps in the total synthesis.

Developing novel catalysts with potent activity is of great importance in organocatalysis. In this study, we designed and prepared a new class of benzotetramisole Lewis base catalysts (AxBTM) that have both central and axial chirality. This unique feature of these catalysts results in a three‐dimensional microenvironment with multi‐layers of chirality. The performance of the developed catalysts was tested in a series of cycloaddition reactions. These included the AxBTM‐catalyzed (2+2) cycloaddition between α‐fluoro‐α‐aryl anhydride with imines or oxindoles, and the sequential gold/AxBTM‐catalyzed (4+2) cycloaddition of enynamides with pentafluorophenyl esters. The interplay between axial and central chirality had a collaborative effect in regulating the stereochemistry in these cycloadditions, leading to high levels of stereoselectivity that would otherwise be challenging to achieve using conventional BTM catalysts. However, the (2+2) and (4+2) cycloadditions have different predilections for axial and central chirality combinations. [ABSTRACT FROM AUTHOR]

[3 + 2] Cycloaddition reaction of N-methyltrifluoromethylmethylene nitrone (MFN) and 2E,4E-5-(benzo[1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (BPD) is studied using molecular electron density theory. The Parr functions analysis predicted successfully the local reactivities and consequent regioselectivity. The calculation of the reaction and activation Gibbs free energies confirmed that the formation of the reported major product under the experimental conditions is more favorable both kinetically and thermodynamically. The origin of this diastereoselectivity was explained by employing IGMH analysis. ELF analysis suggests that the reaction proceeds via a two-stage one-step mechanism and single bonds are formed via coupling of the pseudoradical centers and polarization of the non-bonding electrons. [ABSTRACT FROM AUTHOR]

We herein successfully demonstrate the use of chiral isochalcogenoureas as Lewis Base catalysts for a variety of (4+2)‐cycloaddition reactions of allenoates and different Michael acceptors. In all cases the same structural key‐motive, a dihydropyran with a (Z)‐configurated exocyclic double bond could be accessed as the major regio‐ and diastereoisomer in an enantioselective manner. Furthermore, these chiral dihydropyrans were successfully engaged in different follow‐up transformations. [ABSTRACT FROM AUTHOR]

Within a medicinal chemist's toolbox, one of the most effective strategies to improve the overall properties of a biologically active compound is bioisosteric replacement. Ever since the first example of replacing benzene with a bicyclo[1.1.1]pentane (BCP) group was published in the late 1990s,[1] the medicinal chemistry community has continually been expanding the scope of such phenyl bioisosteric replacements. Recent interest from academia has focused on novel synthetic strategies to access C(sp3)‐rich bicyclic hydrocarbons with expanded ring sizes. Herein, we summarize some of these transformations and reveal that most rely on strain releasing cycloadditions with bicyclo[1.1.0]butane (BCB) and bicyclo[2.1.0]pentane (housane). We have organized this review based on the mechanism of such strain release strategies, namely, carbene cycloadditions, energy transfer photocatalyzed cycloadditions, electron transfer catalyzed cycloadditions, and polar cycloadditions. [ABSTRACT FROM AUTHOR]

The regioselective functionalization of fullerenes holds significant promise for applications in the fields of medicinal chemistry, materials science, and photovoltaics. In this study, we investigate the regioselectivity of the rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions between diynes and C70 as a novel procedure for generating C70 bis(fulleroid) derivatives. The aim is to shed light on the regioselectivity of the process through both experimental and computational approaches. In addition, the photooxidation of one of the C–C double bonds in the synthesized bis(fulleroids) affords open-cage C70 derivatives having a 12-membered ring opening.

The rapid assembly of valuable cyclic amine architectures in a single step from simple precursors has been recognized as an ideal platform in term of efficiency and sustainability. Although a vast number of studies regarding cyclic amine synthesis has been reported, new synthetic disconnection approaches are still high in demand. Herein, we report a catalytic radical‐polar crossover cycloaddition to cyclic amine synthesis triggered from primary sulfonamide under photoredox condition. This newly developed disconnection, comparable to established synthetic approaches, will allow to construct β, β‐disubstituted cyclic amine and β‐monosubstituted cyclic amine derivatives efficiently. This study highlights the unique utility of primary sulfonamide as a bifunctional reagent, which acts as a radical precursor and a nucleophile. The open‐shell methodology demonstrates broad tolerance to various functional groups, drug derivatives and natural products in an economically and sustainable fashion. [ABSTRACT FROM AUTHOR]

The first systematic exploration of the synthesis and reactivity of naphthoquinonynes is described. Routes to two regioisomeric Kobayashi‐type naphthoquinonyne precursors have been developed, and the reactivity of the ensuing 6,7‐ and 5,6‐aryne intermediates has been investigated. Remarkably, these studies have revealed that a broad range of cycloadditions, nucleophile additions and difunctionalizations can be achieved while maintaining the integrity of the highly sensitive quinone unit. The methodologies offer a powerful diversity oriented approach to C6 and C7 functionalized naphthoquinones, which are typically challenging to access. From a reactivity viewpoint, the study is significant because it demonstrates that aryne‐based functionalizations can be utilized strategically in the presence of highly reactive and directly competing functionality. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Heterodienes in organic synthesis," discusses the chemistry and applications of heterodienes in organic synthesis. Heterodienes are vinylogous systems that have unique reactivity and structure. They are commonly used in reactions such as Michael addition, cycloadditions, annulations, and cascade reactions. Heterodienes are also involved in the biosynthesis of natural compounds and can be used in bioconjugation chemistry. The article includes research on specific types of heterodienes, such as azoalkenes and nitroso- and nitroalkenes, and their reactions with various nucleophiles. The authors conclude that the chemistry of heterodienes is an exciting and challenging research area with many more discoveries to be made. [Extracted from the article]

Trifluoromethyl cationic carbyne (CF3C+:) possessing dual carbene‐carbocation behavior emulated as trifluoromethyl metal‐carbynoid (CF3C+=M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α‐diazotrifluoroethyl sulfonium salt was prepared and used in Rh‐catalyzed three‐component [2+1+2] cycloadditions for the first time with commercially available N‐fused heteroarenes and nitriles, yielding a series of imidazo[1,5‐a] N‐heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh‐carbynoid (CF3C+=Rh) into C=N bonds of N‐fused heteroarenes was involved. This strategy demonstrates synthetic applications in late‐stage modification of pharmaceuticals, construction of CD3‐containing N‐heterocycles, gram‐scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5‐a] N‐heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Developing fluorogenic probes for simultaneous live cell labeling of multiple targets is crucial for understanding complex cellular events. The emerging [4+1] cycloaddition between tetrazine and isonitriles holds promise as a bioorthogonal tool, yet existing tetrazine probes lack reactivity and fluorogenicity. Here, we present the development of a series of tetrazine‐functionalized bioorthogonal probes. By incorporating pyrazole adducts into the fluorophore scaffolds, the post‐reacted probes displayed remarkable fluorescence turn‐on ratios, up to 3184‐fold. Moreover, these modifications are generalizable to various fluorophores, enabling a broad emission range from 473 to 659 nm. Quantum chemical calculations further elucidate the turn‐on mechanisms. These probes enable the simultaneous labeling of multiple targets in live cells, without the need for a washing step. Consequently, our findings pave the way for advanced multiplex imaging and detection techniques for cellular studies. [ABSTRACT FROM AUTHOR]

The mechanism of the enantioselective (4+3) cycloaddition between furan derivatives and oxyallylcations, which are generated from the corresponding oxiranes through in situ oxidation of allenamides, has been studied using DFT methods. The research has revealed that, under acid‐catalysis by a chiral non‐racemic phosphoramide, the epoxide ring‐opening proceeds without any energy barrier, while the rate‐limiting step is the electrophilic attack of the intermediate enaminium ion on the furan ring. The reaction exhibits low energy barriers when dealing with furan derivatives unsubstituted at C2 and C5. Calculations predict the formation of an achiral regioisomer for 2‐substituted furans, a prediction that has been experimentally confirmed. Additionally, the calculations accurately predict the reaction with substituted allenamides. [ABSTRACT FROM AUTHOR]

We report that a gem‐dimethylated N‐heterocyclic olefin (NHO) reacts with N2O at ambient pressure and room temperature to give an imidazolone and an azine formed from intermediately generated 2‐diazopropane. The in situ formation of transient diazopropane was indirectly proven by its engagement in a facile cycloaddition with norbornene. According to our studies, the reaction sequence consists of a rate‐determining (3+2) cycloaddition between the NHO and N2O, followed by a cycloreversion that releases the diazoalkane. This mechanistic proposal is supported by DFT calculations. Eyring analysis using temperature‐variable 1H NMR spectroscopy allowed us to determine the activation parameters of the initial (3+2) cycloaddition (Δ≠H=11.2(4) kcal/mol, Δ≠S=−39.8(13) e.u. 293–308 K). Frontier molecular orbital analysis shows that the polarization of the π‐bond of the NHO decisively facilitates the cycloaddition. [ABSTRACT FROM AUTHOR]

Fullerene exhibits a wealth of interesting characteristics owing to its unique π‐electron configuration. The structure and properties of fullerene can be manipulated by introducing chemical groups to the carbon–carbon bonds via organic reactions, extending its application field. The Diels–Alder (DA) cycloaddition reaction is commonly used to decorate the carbon cage of fullerene. Furthermore, atoms, ions, clusters, and molecules can be inserted into the hollow carbon cage of a fullerene, thereby changing the electron transfer process within the fullerene cage and thus the reactivity of the as well as the regioselectivity of the DA cycloaddition reaction. Computer‐based theoretical modeling is an essential tool for studying chemistry. Herein, we provide a brief review of theoretical investigations into the cycloaddition mechanism of two most common fullerenes (C60 and C70), especially in terms of the effects of encapsulated chemical species based on the distortion–interaction model. We hope that the current mini review will provide a useful and interesting resource for researchers working on—or simply being interested in—the in silico investigation of fullerenes and their DA‐based modification. [ABSTRACT FROM AUTHOR]

Access to complex three-dimensional molecular architectures via dearomatization of ubiquitous aryl rings is a powerful synthetic tool, which faces, however, an inherent challenge to overcome energetic costs due to the loss of aromatic stabilization energy. Photochemical methods that allow one to populate high-energy states can thus be an ideal strategy to accomplish otherwise prohibitive reaction pathways. We present an original dearomative rearrangement of heteroaryl acryloylallenamides that leads to complex fused tricycles. The visible-light-promoted method occurs under mild conditions and tolerates a variety of functional groups. According to DFT modeling used to rationalize the outcome of the cascade, the reaction involves a sequential [2+2] allene–alkene photocycloaddition, which is followed by a selective retro- [2+2] step that paves the way for the dearomatization of the heteroaryl partner. This scenario is original with respect to the reported photochemical reactivity of similar substrates and thus holds promise for ample future developments. [ABSTRACT FROM AUTHOR]

Stefano Marcaccini was one of the pioneers in the use of isocyanide-based multicomponent reactions in organic synthesis. Throughout his career at the University of Florence he explored many different faces of isocyanide chemistry, especially those geared towards the synthesis of biologically relevant heterocycles. His work inspired many researchers who contributed to other important developments in the field of multicomponent reactions and created a school of synthetic chemists that continues today. In this manuscript we intend to review the articles on isocyanide multicomponent reactions published by Dr. Marcaccini and analyse their influence on the following works by other researchers. With this, we hope to highlight the immense contribution of Stefano Marcaccini to the development of isocyanide chemistry and modern organic synthesis as well as the influence of his research on future generations. We believe that this review will not only be a well-deserved tribute to the figure of Stefano Marcaccini, but will also serve as a useful inspiration for chemists working in this field. [ABSTRACT FROM AUTHOR]

Leveraging the unique reactivity profile of donor-acceptor aminocyclopropanes and cyclobutanes allows the preparation of complex nitrogen-substituted molecules. While most reports focus on donor-acceptor strained rings with two geminal carbonyl groups as acceptors, mono carbonyl acceptor systems, despite their synthetic relevance, have been considerably less studied. Herein we describe catalytic annulation reactions ofaminocyclopropane and aminocyclobutane monoesters employing silylium catalysis to activate these less reactive donor-acceptor systems.

Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the first example of allenoate activation by using chiral isochalcogenoureas (IChU) for formal (4+2) cycloaddition reactions. Compared to established phosphine and amine catalysis, the use of these easily available Lewis bases enables new stereoselective reaction pathways proceeding with high enantioselectivities, diastereoselectivities, and in good yields. In addition, the factors governing enantioselectivity and the origin of the observed differences compared to other commonly used Lewis bases are explained. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of functionalized spirooxindole polycycles, which are found in many bioactive natural products. The authors describe strategies for the concise synthesis of these complex molecules, including enantiomerically enriched derivatives. They utilize cyclic 1,3-dione derivatives as reactants or as condition-tuning molecules to form the polycyclic systems. The article also explores the formation of spirooxindole pyran polycycles through dynamic stereoselective aldol-oxacyclization cascade reactions. Additionally, the authors discuss the asymmetric construction of spirooxindole polycycles bearing furan-fused rings through Michael-Henry reactions. The use of cyclic 1,3-dione derivatives is shown to alter the reaction conditions and products. The authors conclude by highlighting the potential applications of their synthesis strategies in drug discovery and biomedical research. [Extracted from the article]

This study shows the first example of cycloaddition–retro‐electrocyclization (CA‐RE) click reaction involving nitrogen end‐capped push‐pull oligoynes. The reported CA‐RE reaction with TCNE (tetracyanoethylene) is fully regioselective and leads exclusively to the unprecedented TCBD (tetracyanobuta‐1,3‐diene‐2,3‐diyl) end‐capped carbon rods. The molecular structure of the products was unambiguously confirmed using X‐ray single crystal diffraction and their optical and electronic properties were investigated experimentally and rationalized using DFT (density functional theory) calculations. [ABSTRACT FROM AUTHOR]

Radiolabeled 1,2,4,5-tetrazines are powerful heterocyclic agents for bioorthogonal PET imaging due to their fast cycloaddition with trans-cyclooctenes. However, fluorine-18 radiolabeling of highly reactive tetrazines is often not feasible due to limited compound stability. We demonstrate that post-radiolabeling oxidation of thioether functionalities is a viable and transferable strategy to avoid these limitations, enabling the synthesis of highly reactive 18F-tetrazines. [ABSTRACT FROM AUTHOR]

Inverse electron-demand Diels–Alder additions (iEDDA) between 1,2,4,5-tetrazines and suitable unsaturated dienophiles such as olefins, alkynes, or enol ethers provide facile access to pyridazines. Herein the use of cyclic enol ether derivatives for preparing pyridazines bearing 2-hydroxyethyl, 3-hyproxypropyl, and 3-oxopropyl substituents at the 4-position is disclosed and second order rate constants for the reactions with 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, and 2-methoxy-3,4-dihydro-2H-pyran are presented. [ABSTRACT FROM AUTHOR]

We report a computational and experimental study of the reaction of oxadiazinones and strained alkynes to give polycyclic aromatic hydrocarbons (PAHs). The reaction proceeds by way of a pericyclic reaction cascade and leads to the formation of four new carbon-carbon bonds. Using M06-2X DFT calculations, we interrogate several mechanistic aspects of the reaction, such as why the use of non-aromatic strained alkynes can be used to access unsymmetrical PAHs, whereas the use of arynes in the methodology leads to symmetrical PAHs. In addition, experimental studies enable the rapid synthesis of new PAHs, including tetracene and pentacene scaffolds. These studies not only provide fundamental insight regarding the aforementioned cycloaddition cascades and synthetic access to PAH scaffolds, but are also expected to enable the synthesis of new materials.

Strained cyclic allenes, first discovered in 1966 by Wittig and co-workers, have recently emerged as valuable synthetic building blocks. Previous experimental investigations, and computations reported here, demonstrate that the Diels-Alder reactions of furans and pyrroles with 1,2-cyclohexadiene and oxa- and azaheterocyclic analogs proceed with endo selectivity. This endo selectivity gives the adduct with the allylic saturated carbon of the cyclic allene endo to the diene carbons. The selectivity is very general and useful in synthetic applications. Our computational study establishes the origins of this endo selectivity. We analyze the helical frontier molecular orbitals of strained cyclic allenes and show how secondary orbital and electrostatic effects influence stereoselectivity. The LUMO of carbon-3 of the allene (C-3 is not involved in primary orbital interactions) interacts in a stabilizing fashion with the HOMO of the diene in such a way that the carbon of the cyclic allene attached to C-1 favors the endo position in the transition state. The furan LUMO, allene HOMO interaction reinforces this preference. These mechanistic studies are expected to prompt the further use of long-avoided strained cyclic allenes in chemical synthesis.

The preparation of bridged bicyclooctadienes through the dearomatization of simple arenes is an interesting synthetic tool to access a vast chemical space of elegant molecular architectures from a wide range of simple and cheap building blocks. However, the energetic toll due to the loss of the aromatic stabilization has greatly limited the development of para-cycloadditions, especially with respect to intermolecular processes. We report herein the first general approach for the selective dearomatization of simple naphthalene. The visible-light-promoted reaction occurs under mild conditions over an ample range of substrates and it involves the initial sensitization of an acylallenamide. Moreover, complete control on the difunctionalization of either the internal or the terminal C–C double bond is observed depending on the substrate functionalization.

1,2‐Cyclohexadienes generated under mild fluoride‐mediated desilylative conditions undergo efficient intramolecular [2+2] trapping, providing tricyclic alkylidene cyclobutanes with complete diastereoselectivity for the cis‐fused products. Pendent styrenes or electron‐deficient olefins can trap simple 1,2‐cyclohexadienes or their oxygenated counterparts, with 14 substrates being disclosed. Reactions proceed at ambient temperature using just cesium fluoride in up to 91 % yield, and the necessary precursors are easily accessed from substituted 2‐bromocyclohexenones. Multiple synthetic routes have been developed to install the appropriate functional groups required for [2+2] trapping. [ABSTRACT FROM AUTHOR]

Synthesis and applications of fluoroalkyl and fluoroalkenyliodonium salts are summarized in this account article, focusing preferably to the reagents designed in our laboratory in the last decade. Among these reagents trifluoroethyl(aryl)iodonium salts have been used most frequently to build carbon‐carbon and carbon‐heteroatom bonds in simple nucleophilic substitutions and through transition metal catalyzed coupling reactions. Iodonium salts equipped with unsaturated fluorinated function showed diverse reactivity due to their electron deficient character, and these molecular motifs enable cycloadditions and nucleophilic additions to prepare fluorinated carbo‐ and heterocyclic molecules. Beyond the overview of existing transformations, with the presented collection, we aim to inspire future developments of iodonium reagents and their application in organic synthesis. [ABSTRACT FROM AUTHOR]

An efficient domino approach has been developed for the synthesis of polyheterocyclic derivatives constituting pyrrole moiety. Lewis acid catalyzed reaction of 2‐substituted‐2‐hydroxy‐indane‐1,3‐diones and 1,4‐benzoxazinone derivatives resulted in the formation of polyheterocyclic compounds under metal‐free and mild conditions in good to excellent yield. The reaction is highly regioselective for C−C and C−N bond construction proceeded via intramolecular [3+2] cycloaddition reaction. The protocol is highly efficient, obviates column chromatography and the products are obtained by simple filtration followed by washing with solvent. [ABSTRACT FROM AUTHOR]

Heteroatom-heteroatom bonds tend to be weaker than C-C, C-H, and C-heteroatom bonds and within this broad subset nitrogen-oxygen bonds have a long history of enabling a wealth of interesting reactivity in organic chemistry. 4 Progress toward a Total Synthesis of (-)-Tetrodotoxin In the cases described above, preinstallation of N-O bonds facilitated functionalization of diverse substrates; however, a reaction that forges carbon-nitrogen and carbon-oxygen bonds while retaining a nitrogen-oxygen bond not only introduces dense functionality in short order, but also allows for downstream modifications of complex scaffolds. Keywords: amination; catalysis; sigmatropic reactions; total synthesis; tetrodotoxin; cycloadditions EN amination catalysis sigmatropic reactions total synthesis tetrodotoxin cycloadditions 1563 1572 10 07/31/23 20230815 NES 230815 Graph 1 Introduction Exothermic reactions occur through the exchange of weaker bonds for stronger bonds; consequently, a key element in the design of new transformations is the obligatory accounting of sufficient driving force on the bond-breaking side of the thermodynamic ledger. Development of New Reactions Driven by N-O Bond Cleavage: from O -Acyl Hydroxylamines to Tetrodotoxin. [Extracted from the article]

A convenient one‐step synthesis of β‐aminocyclobutane monoesters starting from commercially available reagents is reported. The obtained strained rings undergo (4+2) dearomative annulation with indole partners using silylium catalysis. This organocatalyzed annulation provided tricyclic indolines with four new stereocenters in up to quantitative yield and >95 : 5 diastereoselectivity and can proceed both intra‐ and intermolecularly. When performed intramolecularly, the tetracyclic structure of either akuamma or malagasy alkaloids was obtained selectively depending on the temperature of the reaction. This divergent outcome could be rationalized based on DFT calculations. [ABSTRACT FROM AUTHOR]

Herein, we report a novel protocol for the direct synthesis of 1,3‐oxathiolan‐5‐ones based on the (3+2)‐cycloaddition between thioketones and acetylenedicarboxylic acid. The products were obtained in a one‐pot reaction within short reaction times and in typically very good yields. The product structure was confirmed by X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]

The isocyano group is a structurally compact bioorthogonal functional group that reacts with tetrazines under physiological conditions. Now it is shown that bulky tetrazine substituents accelerate this cycloaddition. Computational studies suggest that dispersion forces between the isocyano group and the tetrazine substituents in the transition state contribute to the atypical structure-activity relationship. Stable asymmetric tetrazines that react with isonitriles at rate constants as high as 57 L mol-1  s-1 were accessible by combining bulky and electron-withdrawing substituents. Sterically encumbered tetrazines react selectively with isonitriles in the presence of strained alkenes/alkynes, which allows for the orthogonal labeling of three proteins. The established principles will open new opportunities for developing tetrazine reactants with improved characteristics for diverse labeling and release applications with isonitriles.

The chemistry of strained cyclic alkynes has undergone a renaissance over the past two decades. However, a related species, strained cyclic allenes, especially heterocyclic derivatives, have only recently resurfaced and represent another class of valuable intermediates. We report a mild and facile means to generate the parent 3,4-oxacyclic allene from a readily accessible silyl triflate precursor, and then trap it in (4+2), (3+2), and (2+2) reactions to provide a variety of cycloadducts. In addition, we describe a catalytic, decarboxylative asymmetric allylic alkylation performed on an α-silylated substrate, to ultimately permit access to an enantioenriched allene. Generation and trapping of the enantioenriched cyclic allene occurs with complete transfer of stereochemical information in a Diels-Alder cycloaddition through a point-chirality, axial-chirality, point-chirality transfer process.

We describe a novel type of photoclick reaction between 2,3‐diaryl indenone epoxide (DIO) and ring‐strained dipolarophiles, in which DIO serves as a P‐type photoswitch to produce mesoionic oxidopyrylium ylide (PY) to initiate an ultra‐fast [5+2] cycloaddition (k2hν=1.9×105 M−1 s−1). The photoisomerization between DIO and PY can be tightly controlled by either 365 or 520 nm photo‐stimulation, which allows reversion or regeneration of the reactive PY dipole on demand. Thus, this reversible photoactivation was exploited to increase the chemoselectivity of the [5+2] cycloaddition in complex environments via temporal dual‐λ stimulation sequences and to recycle the DIO reagent for batch‐wise protein conjugation. A dynamic photoswitching strategy is also proposed to compensate for molecular diffusion of PY in aqueous solution, enhancing the spatial resolution of lithographic surface decoration and bioorthogonal labeling on living cells via a spatiotemporal dual‐λ photo‐modulation. [ABSTRACT FROM AUTHOR]

Heterocycles containing group 13 and 15 elements such as borazines are an integral part of organic, biomedical and materials chemistry. Surprisingly, heterocycles containing P and Al are rare. We have now utilized phosphaalumenes in reactions with alkynes, alkenes and conjugated double bond systems. With sterically demanding alkynes 1,2‐phosphaalumetes were afforded, whereas the reaction with HCCH or HCCSiMe3 gave 1,4‐phosphaaluminabarrelenes. Using styrene saturated 1,2‐phosphaalumates were formed, which reacted further with additional styrene to give different regio‐isomers of 1,4‐aluminaphosphorinanes. Using ethylene, a 1,4‐aluminaphosphorinane is obtained, while with 1,3‐butadiene a bicyclic system containing an aluminacyclopentane and a phosphirane unit was synthesized. The experimental work is supported by theoretical studies to shed light on the mechanism governing the formation of these heterocycles. [ABSTRACT FROM AUTHOR]

Here, we demonstrate a short synthetic route to pyrano cage systems containing pentacycloundecane units by employing ring-closing metathesis (RCM) as a key step. These cage systems were constructed starting with readily available starting materials by adopting atomic economic processes such as cycloadditions (Diels-Alder reaction and [2+2] cycloaddition), Grignard addition, and olefin metathesis. The key building block, such as hexacyclic cage dione, was prepared from 1,4-naphthoquinone derivative and freshly cracked 1,3-cyclopentadiene. Some of these heterocyclic motifs are useful in biological chemistry and valuable as key synthons for high-energy-density materials. [ABSTRACT FROM AUTHOR]

The design and synthesis of persistent tetraaryl[4]cumulenes are reported. Derivatives with phenyl endgroups ([4]Ph and [4]Ph/Ar*) are susceptible to reactions during synthesis and/or purification that complicate isolation of the desired product, particularly intermolecular dimerization reactions. Incorporation of (3,5‐di‐tert‐butyl)phenyl endgroups (Ar*) provides increased stability, culminating in the stable and isolable [4]cumulene [4]Ar*. Cumulene [4]Ar* remains, however, susceptible to dimerization under pressing conditions, and [4]Ar* also readily reacts with electrophiles under mild conditions that lead to intramolecular cyclization. Given the structural complexity of the side products in these studies (compounds 3, 10, 14, 17, 18), X‐ray crystallography plays a vital role in their identification. [ABSTRACT FROM AUTHOR]

A [Cp*RhCl2]2‐catalyzed formal [3+3]‐cycloaddition involving sequential ring opening of aziridines initiated by C−H activation and Michael addition has been developed for the construction of cis‐1,4‐disubstitued tetrahydro‐γ‐carbolines. The advantages of this strategy include broad substrate scope, excellent cis‐diastereoselectivities, highly functionalized products, and mild conditions. [ABSTRACT FROM AUTHOR]

This review covers articles published in the period from 2010 to mid-2022 on synthetic advances in the formation of pyrimidine and related heterocyclic compounds. Special emphasis has been given to the different types of cycloadditions, taking into account the number of their components and leading to the formation of the pyrimidine ring. Due to the large number of publications on the Biginelli reaction and related reactions, this will be dealt with in a separate review in the near future. [ABSTRACT FROM AUTHOR]