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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]

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]

Here we report a microfluidic system for photochemical cycloadditions fabricated using silicon micro processing technologies. The system was optimized to yield residence times of just a few minutes for a range of photochemical [2+2]-cycloaddition reactions facilitated using high power UV-LEDs at 375 nm and triplet photosensitizers, which removed the need for the low wavelengths typically required for these types of transformations. Adducts using different excitable olefins with different linear, carbocyclic, and heterocyclic coupling partners were explored to demonstrate the feasibility of performing photochemistry in microflow in an academic research environment. Finally, a reaction leading to a novel dihydrooxepin-2(3 H)-one scaffold and a mechanistic proposal for its formation are reported. [ABSTRACT FROM AUTHOR]

A highly efficient [2+2] cycloaddition between maleimides and unsaturated moieties, utilizing a visible-light triplet sensitization mode, has been developed for the direct synthesis of multifunctional 3-azabicyclo[3.2.0]heptane derivatives. This reaction relies on selective activation of the maleimide functionality upon energy transfer from a new photosensitizer that outperforms diverse well-established photosensitizers. The strategy developed herein overcomes previous obstacles such as limited substrate scope and undesired reaction pathways under harsh UV irradiation. [ABSTRACT FROM AUTHOR]

The ability of highly energetic metal–carbene intermediates to engage in complex cascade or formal cycloaddition processes is one of the most powerful tools for building intricate molecular architectures in a straightforward manner. Among this type of organometallic intermediates, non-acceptor metal carbenes are particularly challenging to access and, therefore, have experienced slower development. In this regard, our group has exploited the use of electrophilic gold(I) complexes to selectively activate certain classes of substrates for the generation of this type of intermediate. Thus, very different types of molecules, such as enynes or 7-substituted cycloheptatrienes, lead to the formation of carbenes under gold(I) catalysis. Related rhodium(II) carbenes can also be generated from cycloheptatrienes. In this account, we aim to summarize our efforts towards the in situ generation of such highly versatile organometallic species as well as studies on their reactivity through formal cycloadditions or complex cascade reactions. 1 Introduction 2 Generation of Au(I)-Vinylcarbenes via a Cycloisomerization/1,5-Alkoxy Migration Cascade 2.1 Intramolecular Trapping of Au(I) Vinylcarbenes 2.1.1 Applications in Total Synthesis 2.2 Intermolecular Trapping of Au(I) Vinylcarbenes 2.2.1 Total Synthesis of Schisanwilsonene A 2.2.2 Trapping with Furans, 1,3-Dicarbonyl Compounds and Cyclic Alkenes 2.2.3 Mechanism of the Cycloisomerization/1,5-Migration Sequence and the Role of the OR Migrating Group 2.2.4 (4+3) Cycloadditions from Enynes 3 Formal Cycloadditions of Simple Donor Metal Carbenes 3.1 The Metal-Catalyzed Retro-Buchner Reaction 3.2 Formal Cycloadditions with Non-Acceptor Carbenes via Metal-Catalyzed Aromative Decarbenations 3.2.1 (4+1) Cycloadditions of Au(I) Carbenes 3.2.2 (3+2) Cycloadditions of Au(I) Carbenes 3.2.3 (4+3) Cycloadditions of Rh(II) Carbenes 4 Concluding Remarks [ABSTRACT FROM AUTHOR]

Tertiary enamides display versatile reactivity and great stability compared to their enamine congeners. This review covers progress made in the development of new methods involving the enaminic reactivity of tertiary enamides with respect to the synthesis of complex nitrogen-containing compounds. A focus on the preparation of biologically active molecules is also presented. The syntheses reported herein are classified based on their reaction type. In addition, mechanistic insights are given for most of the new transformations. 1 Introduction 2 [2+2] Cycloadditions 3 [4+2] Cycloadditions 4 Electrocyclizations and Cycloisomerizations 5 Sigmatropic Rearrangements 6 Nucleophilic Additions 7 Tertiary Enamides as Electrophiles 8 Cross-Coupling Reactions 9 Tertiary-Enamide-Assisted Reactions 10 Conclusion and Perspectives [ABSTRACT FROM AUTHOR]

1,3,5-Trisubstituted 1,3,5-triazinanes (hexahydro-1,3,5-triazines), as stable and readily available surrogates for formaldimines, have found extensive applications for the construction of various nitrogen-containing compounds. The formaldimines, formed in situ from this reagent class, can participate in various aminomethylation and cycloaddition- reactions. This short review presents recent advances in this field with emphasis on the conceptual ideas behind the developed methodologies and the reaction mechanisms. 1 Introduction 2 Aminomethylations with 1,3,5-Triazinanes 3 Cycloadditions with 1,3,5-Triazinanes 3.1 Use of 1,3,5-Triazinanes as Two-Atom Synthons 3.2 Use of 1,3,5-Triazinanes as Three-Atom Synthons 3.3 Use of 1,3,5-Triazinanes as Four-Atom Synthons 3.4 Use of 1,3,5-Triazinanes as Six-Atom Synthons 4 Conclusions [ABSTRACT FROM AUTHOR]

The isocyano group is the structurally most compact bioorthogonal group known. It reacts with tetrazines under physiological conditions and has great potential for widespread use in the biosciences. In this account, we highlight the unique properties of the isocyano group as a bioorthogonal functionality. Protecting group chemistry based on the reaction of isonitriles and tetrazines that allows releasing payloads is a particular focus of the article. We further discuss the atypical steric attractions that take place in the transition state of the reaction between isonitriles and tetrazines, which result in an increase in the rate of the reaction with steric bulk of the tetrazine substituents. These findings will open up new possibilities in bioorthogonal chemistry where reactivity and stability are simultaneously desired. 1 Introduction 2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry 3 Bioorthogonal Protecting Group Chemistry 4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles and Tetrazines 5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living Organisms 6 Conclusions [ABSTRACT FROM AUTHOR]

We have summarized diverse synthetic approaches for the modification of peptides by employing transition-metal-catalyzed reactions. These methods can deliver unusual peptides suitable for peptidomimetics. To this end, several popular reactions such as Diels–Alder, 1,3-dipolar cycloaddition, [2+2+2] cyclotrimerization, metathesis, Suzuki-–Miyaura cross-coupling, and Negishi coupling have been used to assemble modified peptides by post-assembly chemical modification strategies. 1 Introduction 2 Synthesis of a Cyclic α-Amino Acid Derivative via a Ring-Closing Metathesis Protocol 3 Peptide Modification Using a Ring-Closing Metathesis Strategy 4 Peptide Modification via a [2+2+2] Cyclotrimerization Reaction 5 Peptide Modification by Using [2+2+2] Cyclotrimerization and Suzuki Coupling 6 Peptide Modification via a Suzuki–Miyaura Cross-Coupling 7 Peptide Modification via Cross-Enyne Metathesis and a Diels–Alder- Reaction as Key Steps 8 Peptide Modification via 1,3-Dipolar Cycloaddition Reactions 9 Modified Peptides via Negishi Coupling 10 A Modified Dipeptide via Ethyl Isocyanoacetate 11 Conclusions [ABSTRACT FROM AUTHOR]

Although the first example of copper-catalyzed azomethine imine--alkyne cycloaddition (CuAIAC) was published only a year after the seminal papers of Meldal and Sharpless on Cu-catalyzed azide-- alkyne cycloaddition (CuAAC), the CuAIAC reaction has remained overlooked by the synthetic community for almost a decade. Since 2010, however, CuAIAC reaction started to emerge as a promising supplement to the well-known CuAAC reaction. The present review surveys primarily the literature on CuAIAC reaction since 2003. Beside this, azomethine imine--alkyne cycloadditions catalyzed by other metals, selected examples of metal-free reactions, and related [3+3] and [3+4] cycloadditions of azomethine imines are presented. All these experimental data indicate the viability of CuAIAC in organic synthesis and the applicability in 'click' chemistry. 1 Introduction 2 Reactions with Acyclic Azomethine Imines 3 Reactions with C,N-Cyclic Azomethine Imines 4 Reactions with N,N-Cyclic Azomethine Imines 5 Reactions with C,N,N-Cyclic Azomethine Imines 6 The Mechanism of the CuAIAC Reaction 7 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

Cyclopentadiene (Cpd) is widely used as a starting material in organic and inorganic chemistry. In neat form, Cpd dimerizes, making it necessary to distill it prior to use to obtain fully reactive material. We have screened three different tetraphenyladamantane octaethers for their ability to act as encapsulating organic crystal (EnOC) hosts for Cpd. To this end, we also synthesized 1,3,5,7-tetrakis(3,5-dimethoxyphenyl) adamantane, a new octaether, dubbed iso-TDA. Only one of the octaethers was found to produce inclusion complexes with Cpd in the crystalline state. The encapsulated diene was stable for one month and showed full reactivity in a series of different synthetic transformations. [ABSTRACT FROM AUTHOR]

N-Sulfonyl ynamido-phosphonates were prepared from sulfonamides and bromo alkynylphosphonates through a direct coppercatalyzed coupling reaction. The substrates were obtained in good to excellent yields. The latter are valuable partners to react with nitrileoxides to form isoxazoles in good yields and with an exclusive regioselectivity. [ABSTRACT FROM AUTHOR]

This review reports the synthesis of propargylic derivatives with alkyl chains bearing either one fluorine or a gem-difluoro system. The preparation of the different categories of fluorinated derivatives is analyzed in a systematic manner, based on the nature of substituents close to the fluorine atom(s). In the second part of this review are summarized the synthetic applications of these fluorinated propargylic intermediates, focusing mainly on the preparation of carbo- and heterocyclic derivatives. [ABSTRACT FROM AUTHOR]

The electrophilic substitution of indoles with tetronic acid and N-acetyltetramic acid mediated by BF3·OEt2 was investigated. This strategy allowed for the preparation of nine indole-substituted furan-2-ones (indolyl-γ-lactones) and 3-pyrrolin-2-ones (indolyl-γ-lactams) and is more straightforward than previously reported synthetic methods. During the course of our investigation, we also discovered a facile synthesis of tetronates and a tetramate via a BF3-mediated addition of alcohols to tetronic acid and N-acetyltetramic acid, respectively. [ABSTRACT FROM AUTHOR]

The desymmetrized meso-chimonantine core of leptosin C was prepared in a short stereoselective convergent sequence in 5 steps as the longest linear path from methyl L-tryptophan hydrochloride as starting material. The key step of this approach was a diastereoselective [4+2] cycloaddition between the bromooxindole and tryptophan derivatives allowing to define the adjacent quaternary benzylic centers in a high chemical yield. [ABSTRACT FROM AUTHOR]

Lewis acid catalyzed cycloaddition reactions of (E)-1-methyl-2-styrylquinolin-4(1H)-ones with the very reactive diene ortho-benzo-quinodimethane, generated in situ by thermal extrusion of sulfur dioxide from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide, afforded trans-2-(3-aryl-1,2,3,4-tetrahydronaphthalen-2-yl)-1-methylquinolin-4(1H)-ones in good yields. Upon DDQ-mediated dehydrogenation these adducts were converted into the corresponding 2-(3-arylnaphthalen-2-yl)-1-methylquinolin-4(1H)-ones. The influence of electron-withdrawing and electron-donating groups on the cycloaddition and dehydrogenation reactions was investigated. [ABSTRACT FROM AUTHOR]

Geminal bis- and tristriazoles belong to a rare and mainly overlooked class of organic compounds with interesting properties. This review summarizes the methods for their preparation. Moreover, applications of these compounds are described, ranging from ring extensions to their use as reactive intermediates for the efficient construction of heterocycles. 1 Introduction 2 Bistriazoles 2.1 Bistriazoles (Tetrahedral Carbon) 2.2 Bistriazoles (Trigonal Carbon) 3 Tristriazoles 4 Conclusion and Prospectives [ABSTRACT FROM AUTHOR]

The exploitation of unnatural amino acid (UAA) technologies represents an excellent mechanism for the generation of site-specific bioconjugates. Consequently, significant effort has been invested in the advancement of the technology via the integration of novel bioconjugation reactions and the expansion of the set of UAAs that can be employed. Herein, we report the recent developments in the field and highlight advantages and disadvantages of various UAA bioconjugation reactions. [ABSTRACT FROM AUTHOR]

This account describes progress in the author's laboratory in the area of new fluorescent polymers that respond to the reactive oxygen species singlet oxygen ¹Cy. Key to the development of these materials are the [4+2] cycloaddition reactions between singlet oxygen and dienes such as acenes and furans. When covalently bound to conjugated polymer backbones, cycloadditions of these dienes with singlet oxygen can yield dramatic changes in the wavelength and intensity of luminescence: three such examples are given here. The account also summarizes our work to understand how changing the chemical structures of acenes affects reactivity with singlet oxygen as well as the cy-cloreversion of the resulting endoperoxides. 1 Introduction 2 Motivation 3 Organic Soluble Diene-Linked Conjugated Polymers 4 Red-Shifting Woes Lead to Reversibility 5 Building a Database 6 Integrating Other Acenes 7 Conclusion and Looking Forward [ABSTRACT FROM AUTHOR]

Three novel helical dications (helquats) containing phenanthridinium units have been synthesized from 6-(pyridin-2-ylethynyl) phenanthridine as a common precursor prepared by Sonogashira coupling of phenanthridin-6-yl triflate with 2-ethynylpyridine. Bisquaternization of the common precursor followed by rhodium-catalyzed [2+2+2] cycloisomerization led to the title helical dicationic scaffolds. The connectivity and spatial arrangement of the three target helquats were unambiguously established by X-ray crystal structure analysis. [ABSTRACT FROM AUTHOR]

Tribenzotropone was efficiently synthesized by a ring-expansion method from readily available phenanthrene-9,10-dione via a ringopened diketone as a key intermediate; the diketone was prepared by nucleophilic addition of allyl and vinyl groups, followed by an oxidative ring-opening reaction with lead(IV) acetate. Ring closure by an intramolecular Diels-Alder reaction and subsequent dehydrogenation produced tribenzotropone in 38% overall yield. Ring closure by a Morita- Baylis-Hillman reaction, on the other hand, produced a dibenzo-fused nonanedione in 22% overall yield. [ABSTRACT FROM AUTHOR]

o-Quinonemethides generated by condensation of 6-methylhept-5-en-2-ol with various salicylaldehydes in the presence of 30 mol% of fluoroboric acid etherate or triflic acid undergo [4+2]-cycloaddition reaction in situ to afford angularly fused pyranochromene derivatives in good yields and excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

A stereoselective synthesis of the complete C1-C16 framework of tianchimycins A and B is described. Key transformations include Horner-Wadsworth-Emmons, Evans aldol, Gilman's and stereoselective alkylation reactions. [ABSTRACT FROM AUTHOR]

Aziridines derived from 2-(prop-2-yn-1-yloxy)- and 2-(buta- 2,3-dien-1-yloxy)chalcones and from benzyl 2-(prop-2-yn-1-yloxy)- and 2-(buta-2,3-dien-1-yloxy)phenylacrylates were prepared in a stereoselective fashion. Their reactivity as azomethine ylide precursors was examined, leading to the synthesis of 1,4-dihydrochromeno[4,3-b]pyrrole and 3-methylenechromano[4,3-b]pyrrole derivatives through intramolecular 1,3-dipolar cycloaddition reactions. [ABSTRACT FROM AUTHOR]

The Diels-Alder reactions of eight different 1,3-dienes incorporated into an 8-oxa- or 8-thiabicyclo[3.2.1]octane backbone were studied employing N-phenylmaleimide as standard dienophile. The facial diastereoselectivity was very high, in all cases furnishing only products resulting from a top-face attack. The [4+2] cycloadditions proceeded often with high exo/endo selectivity depending on the substitution degree of the 1,3-diene system. For one of the 1,3-dienes it could be demonstrated that the scope of the Diels-Alder reaction is fairly broad. The approach described here allows an efficient and fast access to complex tri- and tetracyclic compounds ready for further functionalization. [ABSTRACT FROM AUTHOR]

A series of furanyl-, thiophenyl-, and pyrrolo-substituted pyrroles were prepared via the 1,3-dipolar cycloaddition of unsymmetrical münchnones and nitrovinylheterocycles. The regiochemical outcome of the furan and thiophene cycloadditions compares favorably to previously reported cycloadditions with β-nitrostyrene, while the nitrovinylpyrrole cycloadditions mirror the results observed with nitrovinylindole. [ABSTRACT FROM AUTHOR]

Large polycyclic o-(trimethylsilyl)aryl triflates are easily obtained by reaction of commercially available bisaryne precursors with cyclopentadienones. The transformation involves controlled generation of one of the aryne functionalities, trapping by Diels–Alder reaction with a dienone, and chelotropic extrusion of CO. The newly synthesized triflates are precursors of acene-based arynes, including a didehydropentacene. [ABSTRACT FROM AUTHOR]

Chlorosulfonyl isocyanate (CSI) is a sluggish electrophile in reactions with electron-deficient alkenes or with many monofluoroalkenes. The efficiency of these reactions is improved at temperatures between -15 and 25 °C because, at these temperatures, CSI and the alkene are in equilibrium with an intermediate. A unimolecular reaction of the intermediate at a temperature between -15 and 25 °C is more efficient than the bimolecular reaction of the dissociated reagents above room temperature. This finding provides a method for improving the reactions of CSI with unreactive alkenes. [ABSTRACT FROM AUTHOR]

A simple one-pot multicomponent procedure has been developed for the synthesis of pyrrolo[1,2-a]benzimidazole and pyrrolo[ 1,2-a]quinoxaline derivatives by heating a 1:2:1 molar mixture of a benzimidazole unsubstituted on the imidazole ring, a 2-bromoacetophenone derivative, and a nonsymmetrical activated alkyne in refluxing 2-ethyloxirane. The reaction can be performed under conventional reflux conditions or with microwave irradiation. [ABSTRACT FROM AUTHOR]

We describe a fast and efficient incorporation of the ligands 2-(1H-1,2,3-triazol-4-yl)pyridine and 2-(1H-1,2,3-triazol-1-ylmethyl)-pyridine into N-substituted glycine peptoid oligomers by the azide–alkyne cycloaddition (click) reaction on a solid support under microwave irradiation. Peptoids bearing these ligands formed stable complexes with copper(II). [ABSTRACT FROM AUTHOR]

A general and efficient method has been developed for the synthesis of 1,3-disubstituted 1,3-dihydroimidazo[5,1-b]quinazolin-9-ones. The process involves an intramolecular Mannich­-type reaction of a 2-aminomethylquinazolin-4-one derivative with an aldehyde, and gives diastereomeric mixtures of the minor cis- and major trans-cycloadducts. [ABSTRACT FROM AUTHOR]

Selected developments in the chemistry of heteroaromatic N-oxides since 2001 are presented in this review. The use of these N-oxides, both in late-transition-metal-catalyzed oxidations of carbon-carbon triple bonds and in regioselective C-H functionalizations of the heteroarene, are contemporary topics of interest and the focus of the discussion. 1 Introduction 2 Synthesis of Heteroaromatic N-Oxides 2.1 Direct Oxidation of Hindered Heteroarenes 2.2 Through Construction of Heteroaromatic Rings 3 Heteroaromatic N-Oxides as Oxidants 3.1 Alkyne Oxidation 3.2 Allene Oxidation 3.3 Carbene Oxidation 4 Heteroaromatic N-Oxides as Substrates 4.1 Deoxygenative ortho-C-H Functionalization with Prior Activation 4.2 Deoxygenative ortho-C-H Functionalization with Nonstabilized Carbanions 4.3 Nondeoxygenative C-H Functionalization 4.3.1 ortho-C-H Functionalization 4.3.2 N-Oxide Directed ortho-Alkyl C-H Functionalization 4.3.3 N-Oxide Directed Remote C-H Functionalization 4.4 1,3-Dipolar Cycloaddition 5 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

This review explores the myriad ways in which the Diels-Alder reaction has been employed in the construction of the tetracyclic steroid nucleus. A systematic analysis of possible approaches highlights both the synthetic versatility of this ubiquitous reaction and also opportunities for new routes to fused tetracarbocyclic steroid frameworks. 1.1 Introduction 1.2 Classification of the Approaches 2.1 Installation of a Non-Skeletal Ring 2.2 Construction of the A-Ring 2.3 Construction of the B-Ring 2.4 Construction of the C-Ring 2.5 Double Diels-Alder Sequences 3 Conclusions and Future Prospects [ABSTRACT FROM AUTHOR]

This account covers the chemistry of alkynyl silyl sulfides and their use as substitutes for aldothioketenes. In contrast to the latter heterocumulenes, which can only be prepared and used in situ, many alkynyl silyl sulfides are stable at room temperature. Exceptions are bissilylated derivatives that are capable of rearranging to form the corresponding thioketenes. This reaction is promoted thermally or by the addition of silyl-accepting Lewis bases, but is suppressed by bulky S-silyl substituents. The reactivity of the highly electrophilic alkynyl silyl sulfides is comparable to that of the corresponding ketenes and thioketenes. Nucleophiles usually add to the alkyne α-carbon atoms to give, after desilylation, thiocarbonyl compounds. Particularly useful are the reactions with amines, imines, or ynamines, which give thioamides, β-thiolactams, and cyclobutenethiones, respectively. These transformations proceed under mild conditions and provide access to derivatives that could not previously be prepared by classical means. The scope of the [2+2]-cycloaddition reaction with imines to give β-thiolactams can be expanded by using Lewis acid catalysts, particularly zinc iodide. The mechanism of this reaction has been elucidated by careful characterization of byproducts. Further modifications of the β-thiolactams prepared by this methodology are also described. Reactions of alkynyl silyl sulfides with cyclic imines lead to bicyclic systems that can be considered as thio analogues of the core structures of β-lactam antibiotics. However, there is a competition from the ring-expansion reaction to form seven-membered thiolactams and dithiolactones. 1 Introduction 2 Synthesis of Alkynyl Silyl Sulfides 3 Reactions 3.1 Thioacylation of Amines 3.2 [2+2]-Cycloaddition Reactions with Azomethines 3.3 Cycloaddition Reactions with (Thio)imidates 3.4 Cycloaddition Reactions with Ynamines 4 Conclusions [ABSTRACT FROM AUTHOR]

Recent advances in the diversity of synthetic routes available for the preparation of thiazolothiadiazoles and thiazolooxadiazoles are summarized and reviewed. The relative arrangements of the sulfur, oxygen, and nitrogen atoms and the various positions for fusion between the thiazole or oxazole and thiadiazole rings afford four different subclasses of thiazolothiadiazoles and thiazolooxadiazoles. Methods for synthesizing each of these subclasses are discussed separately. These compounds possess antimicrobial, antitubercular, anticancer, and anticonvulsant activities. The observed biological activities are due to the presence of the thiadiazole moiety, which displays diverse pharmacological activities. This short review can serve as a guide for synthetic and medicinal chemists wishing to develop novel thiazolothiadiazoles and thiazolooxadiazoles that can be evaluated as potential drugs. [ABSTRACT FROM AUTHOR]

The first examples of a convenient domino synthesis of fused yne-functionalized benzoisoindoline derivatives by a copper( I) iodide catalyzed cyclization reaction of simple triynes in a single operation are described. [ABSTRACT FROM AUTHOR]

N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)- benzamide derivatives, a novel class of compounds, were synthesized by 1,3-dipolar cycloaddition of azomethine imines with azlactones and subsequent rearrangement. The reaction can be completed rapidly under mild conditions without a catalyst. [ABSTRACT FROM AUTHOR]

This review presents the recent progress in the chemistry of dimethyl acetylenedicarboxylate (DMAD). The interest in and applications of this powerful reagent with more than 135 years of history have greatly increased in the last 10 years, further proving its versatility. Undoubtedly, DMAD can be a multi-tool in the quest of molecular complexity and diversity. The extreme structural diversity of the products described in this review illustrates the powerful potential of DMAD as a building block in organic synthesis. 1 Introduction 2 Michael Reactions 2.1 Sulfur as Nucleophile 2.2 Nitrogen as Nucleophile 2.3 Oxygen as Nucleophile 2.4 Addition to Carbon-Carbon Double Bonds 3 Cycloaddition Reactions 3.1 Diels-Alder Reactions ([4+2] Cycloadditions) 3.2 1,3-Dipolar Reactions ([3+2] Cycloadditions) 3.3 [2+2] Cycloadditions 3.4 [8+2] Cycloadditions 4 DMAD and the Generation of Zwitterions; Multicomponent Reactions (MCRs) 4.1 Phosphines and Derivatives 4.2 Amines 4.3 Isocyanides 4.4 Carbenes 4.5 Miscellaneous Reactions 5 Conclusion [ABSTRACT FROM AUTHOR]

A formal [3+2] cycloaddition between aziridines and alkenes to give the corresponding pyrrolidines was successfully carried out in the presence of a cationic manganese porphyrin catalyst. The use of the porphyrin catalyst allowed, for the first time, styrene derivatives to react with aziridines. [ABSTRACT FROM AUTHOR]

The efficient generation of complex molecular architectures from simple precursors is one of the most important aspects in the design and development of synthetic methodologies. The chemistry of reactive species generated by the oxidative dearomatization of phenols, such as o-quinone acetals, 6-acetoxycyclohexa-2,4-dienones, and their congeners, has stimulated widespread interest among organic chemists, and the use of such reactive species has emerged as a powerful method for the efficient synthesis of complex molecules. Our approach to create molecular complexity and diversity involves the oxidative dearomatization of 2-(hydroxymethyl)phenols to give spiro[cyclohexa-2,4-dienone-6,2′-oxiranes], followed by cycloaddition and transformation of the resulting adducts in the ground and excited states. In this account, we describe the evolution of the methodology and its application which has led to the development of novel and efficient routes to a diverse array of complex molecular architectures from simple aromatics. [ABSTRACT FROM AUTHOR]

Norbornadiene cycloadducts reacted with 3,6-di(2-pyridyl)- s-tetrazine to produce pyridazines (diene-protected alkenes), following dehydrogenation (by DDQ) of the intermediate dihydropyridazines. The title 3,6-di(2-pyridyl)-pyridazinonorbornadiene was produced under flash vacuum pyrolysis conditions by ejection of anthracene (590 °C), isobenzofuran (630 °C) or isoindole (580 °C) from the corresponding pyridazines, establishing the following dienofugacity order: isoindole > anthracene > isobenzofuran. Calculations of the respective retro-Diels-alder activation energies at the B3LYP/6-31G" level of theory correctly predicted the experimentally found isobenzofuran > anthracene > isoindole order. Cavity bis-3,6-di(2-pyridyl)-pyridazine (dppn) and chevron-shaped bisdppn ligands were prepared from the title compound by coupling at the norbornene π-bond. [ABSTRACT FROM AUTHOR]

A simple one-pot procedure was developed for [3+2]-cycloaddition reactions of a,ß-unsaturated aldehydes, diethyl aminomalonate, and aromatic aldehydes in the presence of diphenyl[(2S)-pyrrolidin-2-yl]methanol as catalyst. This reaction converts simple, commercially available, starting materials into densely functionalized polysubstituted pyrrolidines under mild conditions and in a fully stereoselective fashion. Moreover, the use of brine as the reaction medium has remarkable beneficial effects in preventing the formation of self-condensation byproducts, cutting the reaction time, and reducing the production of wastes. [ABSTRACT FROM AUTHOR]

This account summarizes recent research in our group on the development of N-heterocyclic carbene (NHC) catalyzed cycloaddition reactions of ketenes. The NHCs were found to be efficient catalysts for the enantioselective [2+2]-, [2+2+2]-, [3+2]-, and [4+2]-cycloaddition reactions of ketenes with various electrophiles, such as imines, carbonyl compounds, oxaziridines, oxodienes and azadienes. The NHC-catalyzed [4+2] cycloaddition of α,β-unsaturated acyl chlorides was also investigated. 1 Introduction 2 [2+2] Cycloaddition of Ketenes 2.1 With Carbon-Nitrogen Double Bonds 2.2 With Carbon-Oxygen Double Bonds 2.3 With Oxygen-Nitrogen and Nitrogen-Nitrogen Double Bonds 2.4 With X=Y=Z Bonds 3 [3+2] Cycloaddition of Ketenes 4 [4+2] Cycloaddition of Ketenes 5 [4+2] Annulation of Unsaturated Acyl Chlorides 6 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

A practical and convenient solvent-free iridium-cata-lyzed [2+2+2] cycloaddition of a,ω-diynes and alkynes to prepare fused arenes has been developed. The method has shown high effi-ciency as isoindolines, dihydroisobenzofurans and indanes have been synthesized in good to excellent yields. [ABSTRACT FROM AUTHOR]

The tricyclic ring system with an oxabicyclo[3.2.1]octadiene and a fused six-membered ring was produced efficiently using the readily available propargyl ester furan substrate in the presence of a Au(I) complex. The reaction involves a tandem 3,3-rearrangement of the propargyl ester followed by an intramolecular [4+3]-cycloaddition reaction. Both the primary ligand of the gold complex (N-heterocyclic carbene; NHC) and a neutral dynamic ligand (PhCN) are important for the success of the reaction. [ABSTRACT FROM AUTHOR]

Several systems consisting of a ligand, a metal compound, and zinc have been developed as catalysts for alkyne cycloaddition reactions and alkyne-nitrile co-cycloaddition reactions. NHeterocyclic carbene (NHC)-iron(III) chloride-zinc, NHC-cobalt( II) chloride-zinc, and 2-{[(2,6-diisopropylphenyl)imino]methyl} pyridine (dipimp)-iron(III) chloride hexahydrate-zinc systems catalyzed intramolecular cyclotrimerization reactions of alkynes. The dipimp-cobalt(II) chloride hexahydrate-zinc system catalyzed cycloaddition reactions of a variety of alkynes in intramolecular, partially intramolecular, and fully intermolecular fashions. The ethane- 1,2-diylbis(diphenylphosphine)-cobalt(II) chloride hexahydrate- zinc system was effective in catalyzing the [2 + 2 + 2] cocycloaddition of diynes with nitriles. Nickel complexes with an ionic liquid-tagged ligand converted 1,6-diynes into the corresponding cyclooctatetraenes in a toluene-ionic liquid biphasic system in the presence of zinc. The dipimp-nickel(II) chloride hexahydrate-zinc catalyst polymerized 1,6-diynes to form conjugated polyene cyclic polymers. These results and their applications in synthesis, including controlled polymerization reactions, are described. [ABSTRACT FROM AUTHOR]

The reaction of 6,7-dihydrothieno[3,2-c]pyridine derivatives with 1,3-dipoles, such as a nitrile oxides or nitrile imines, gave novel fused heterocycles. The Staudinger reaction of the starting material was also studied. This reaction was stereoselective and exclusively gave racemic cis-cycloadducts in which the thienopyridine core was fused with a β-lactam ring. [ABSTRACT FROM AUTHOR]

The synthesis of 2,3-disubstituted tetrahydroquinolines has been achieved by first performing a cross-metathesis of different alkenes with readily available N-allyloxycarbonyl-2-chloromethylaniline. Among the catalysts tested, Hoveyda-Grubbs reagent appeared to be the most suitable, reaching the substituted analogues with complete E-stereocontrol and convenient yields. An intramolecular aza-Diels-Alder reaction was further carried out in the presence of potassium phosphate as promoter to deliver the corresponding 2,3-disubstituted tetrahydroquinolines. [ABSTRACT FROM AUTHOR]

In the presence of catalytic amounts of copper salts and sodium ascorbate, various (arylselanyl)alkynes underwent clicktype 1,3-dipolar cycloaddition reactions with a range of benzyl azides bearing electron-withdrawing or electron-donating groups to give a series of novel [(arylselanyl)alkyl]-1,2,3-triazoles. This click chemistry protocol is an efficient method for synthesizing new selenium- nitrogen compounds that are potentially useful in biological studies. [ABSTRACT FROM AUTHOR]

The solvent-free, microwave-assisted 1,3-dipolar cycloaddition of carbonyl ylides, generated from a series of oxiranes, to SWCNTs (single-walled carbon nanotubes) is described. The procedure is extremely fast and repeatable. The reaction of SWCNTs with benzylidenmalononitrile epoxide afforded a gem-dicyano derivative that is well-suited to further transformation into esters or amides through the Pinner reaction. [ABSTRACT FROM AUTHOR]