We show that 2-diynylpyridine and a Bpin-terminated monoyne or diyne will cross-react to form benzyne intermediates. These reactive intermediates are captured by various in situ trapping agents to give products of three-component reactions. Various control reactions, substrate modification, binding studies, and DFT analysis suggest that a small amount of a noncovalent Lewis acid-base complex is the active species within which the diyne and diynophile engage to produce the benzyne.
View Article and Find Full Text PDFCarbenes and carbenoids are commonly employed for the synthesis of cyclopropane-containing compounds. Here we report the metal-free, intramolecular cyclopropanation of tethered alkenes by free carbenes derived from alkynes to construct structurally unique multicyclic cyclopropanes with perfect atom economy. The nature of the tether influences both the rate of carbene formation and subsequent competing reaction events.
View Article and Find Full Text PDFA pyridine containing a 2-alkynyl substituent armed with a carbene reporter group [R = C(Me)OAc] is shown to engage electrophilic allenes to generate intermediate free carbenes. Depending on the electron density at the carbene carbon atom, a feature that is modulated by the substituents on the allene substrate, the carbene will either rearrange or eject an acetate leaving group, leading to various types of indolizine-containing products. Iso(thio)cyanates react in an analogous fashion.
View Article and Find Full Text PDFThe relative reactivity of a systematic series of simple aliphatic acetate esters has been measured. Exposure of pairs of esters of increasing remote steric hindrance (by altering the degree of branching of the ester alkyl group) to a methanolic solution of CsCO proved to be a reliable (and general) method for quantitating the rate differences in these base-catalyzed transesterification reactions. The trends in relative rates are in accordance with the qualitative "Rule of Six" put forward by Melvin S.
View Article and Find Full Text PDF1,3-Dipolar cycloadditions of azoxy species are rare. HOBT exists as a pair of tautomers, one of which contains an azoxy subunit. We show that heavily substituted, thermally generated benzynes react with HOBT by engaging the azoxy tautomer to give products having a benzotriazole with a benzyne-derived -hydroxyaryl group at N2.
View Article and Find Full Text PDFCarbenes (RRC:) like radicals, arynes and nitrenes constitute an important family of neutral, high-energy, reactive intermediates-fleeting chemical entities that undergo rapid reactions. An alkyne (RC≡CR) is a fundamental functional group that houses a high degree of potential energy; however, the substantial kinetic stability of alkynes renders them conveniently handleable as shelf-stable chemical commodities. The ability to generate metal-free carbenes directly from alkynes, fuelled by the high potential (that is, thermodynamic) energy of the latter, would constitute a considerable advance.
View Article and Find Full Text PDFIntramolecular net [2 + 2] cycloadditions between benzyne intermediates and an electron-deficient alkene to give benzocyclobutene intermediates are relatively rare. Benzynes are electrophilic and generally engage nucleophiles or electron-rich π-systems. We describe here reactions in which an alkene of a tethered enone traps thermally generated benzynes in a variety of interesting ways.
View Article and Find Full Text PDF2:1 adducts arise from the reaction of 2,5-diaryl-1,3,4-oxadiazoles and benzynes generated from the hexadehydro-Diels-Alder (HDDA) reaction. Density functional theory computations support a mechanistic manifold that includes a concerted SAr process. Additionally, the benzyne trapping reaction of 2,5-dimethyl-1,3,4-oxadiazole affords an unusual acylimine-containing 2:1 adduct, which is the first case in which a dearomatized product has arisen from a HDDA reaction.
View Article and Find Full Text PDFSesquiterpene lactones (SL) represent a class of secondary metabolites found in the Asteraceae family, notable for their unique structures. The SL α-santonin (1) and its derivatives are worthy of mention due to their diverse biological properties. Additionally, 4H-chromenes and 4H-chromones are appealing frameworks holding the capability to be used as structural motifs for new drugs.
View Article and Find Full Text PDFHere, we report a strain-promoted cascade reaction that proceeds via multiple strained intermediates, ultimately driven by the high potential energy inherent in alkyne triple bonds (C≡C). More specifically, four alkynes (three from an HDDA benzyne precursor and the fourth from a conjugated enyne reaction partner) are transformed into eight of the skeletal carbons in the benzocyclohexadienone products. The reaction pathway proceeds sequentially via strained benzyne, benzocyclobutene, and cyclic allene intermediates.
View Article and Find Full Text PDFThe plant-derived compounds furfuryl alcohol and itaconic anhydride are known to undergo a Diels-Alder reaction at room temperature and in bulk to efficiently give an alkene-containing lactone carboxylic acid. Reported here is the conversion of this substance to a variety of derivatives via hydrogenation, epoxidation, or halolactonization reactions. Most notable is the formation of a set of three related acrylate or methacrylate esters (see graphical abstract) produced by direct acylative ring opening of ether bonds using Sc(OTf) and (meth)acrylic anhydride.
View Article and Find Full Text PDFArynes are fleeting, high-energy intermediates that undergo myriad trapping reactions by nucleophiles. Their unusual reactivity compared to other electrophiles can spur unexpected mechanistic pathways enroute to the formation of benzenoid products. Herein we explore a particularly unique case of thermally generated arynes reacting with phosphoranes to form helical dibenzothiophenes and -selenophenes.
View Article and Find Full Text PDFHeterocyclic substrates containing a conjugated alkyne and a pendant nitrile were shown to cyclize in an overall tetradehydro-Diels-Alder reaction to give products in which the initial heterocycle bears a newly fused pyridine ring. Base-promoted tautomerization of the alkyne to its isomeric allene allows this process to occur at ambient temperature. DFT studies support many of the mechanistic interpretations of the overall results.
View Article and Find Full Text PDFWe report here a study that has revealed two distinct modes of reactivity of azobenzene derivatives (ArN[double bond, length as m-dash]NAr) with benzynes, depending on whether the aryne reacts with a - or a -azobenzene geometric isomer. Under thermal conditions, -azobenzenes engage benzyne an initial [2 + 2] trapping event, a process analogous to known reactions of benzynes with diarylimines (ArC[double bond, length as m-dash]NAr). This is followed by an electrocyclic ring opening/closing sequence to furnish dihydrophenazine derivatives, subjects of contemporary interest in other fields (, electronic and photonic materials).
View Article and Find Full Text PDFThermal processing (e.g., pasteurization and sterilization) is a critical step ensuring the microbial safety of our foods.
View Article and Find Full Text PDFStrained cyclic allenes are reactive species that can be trapped in a variety of complementary fashions that capitalize on their inherent high potential energy. 1,2,4-Cyclohexatrienes represent a subclass of allenes that, notably, can be conveniently generated by a net [4 + 2] cycloaddition within a 1,3-enyne bearing a tethered alkyne via a tetradehydro-Diels-Alder reaction. A limitation to the use of this type of thermally generated cyclic allene as a construct for the introduction of molecular complexity is their propensity to isomerize to benzenoids via a simple net 1,5-hydrogen atom migration.
View Article and Find Full Text PDFThe purpose of this study was to learn if a convenient H NMR method could be developed to serve as a tool for estimating the propensity of a given lactone to participate in ring-opening transesterification polymerization (ROTEP). The methanolysis of each of 18 lactones was initially examined in CDOD solution in the presence of sulfuric acid as a Brønsted catalyst at ambient temperature. Once equilibrium was established, the ratio of remaining lactone to the ring-opened methyl ester/alcohol could be readily measured by NMR spectroscopy.
View Article and Find Full Text PDFThe presence of a nearby tethered functional group (G, G = tertiary amide or amine) can significantly impact the rate of cleavage of an Si-O bond. We report here an H NMR spectroscopic investigation of the relative rates of cleavage of model substrates containing two different Si-O substructures, namely alkoxydisiloxanes [GRO-Si(Me)-O-SiMe] and carbodisiloxanes [GR-Si(Me)-O-SiMe]. The trends in the relative rates (which slowed with increasing chain length, with a notable exception) of alkoxydisiloxane hydrolyses were probed via computation.
View Article and Find Full Text PDFBackground: Some herbal natural products play an important role in protecting organisms from the toxic effect of some xenobiotics. The present study was designed to evaluate the potential therapeutic effects of Ottelione A (OTTE) against carbon tetrachloride(CCl)-induced toxicity in mice.
Methods: Adult male Swiss albino mice were divided into six groups: group I was used as a normal control received olive oil; group II received DMSO; group III received OTTE; group IV received CCl in olive oil, (injected i.
Angew Chem Int Ed Engl
October 2022
We report here the generation of α,3-dehydrotoluenes, a relatively rare subset of reactive intermediates of the dehydroaromatic family, from isolable allenynes. The substructure motif in the allenyne substrates is distinct from, and complementary to, those found in Myers-Saito/Schmittel-type cycloisomerizations. The reactions reported here give rise to product profiles that provide insight about the electronic nature (i.
View Article and Find Full Text PDFThe incorporation of renewable feedstocks into polymer backbones is of great importance in modern polymer science. We report the synthesis of 1,3-diyne polymers derived from the bispropargyl ethers of isosorbide, isomannide, and isoidide. The dialkyne monomers can be polymerized through an adaptation of the Glaser-Hay coupling using a nickel(II) cocatalyst.
View Article and Find Full Text PDFHere we provide examples that demonstrate the value of using properly designed and easily performed doping experiments to give insights about the nature of the analyte(s) present in a H NMR sample. Two mixtures, the first quite complex and the second far less so, have been chosen: (i) the crude pyrolysate from reaction of butyric acid in (supercritical) water at 600 °C and (ii) a mixture of two basic amines. In the former, 13 distinct carbonyl-containing compounds, ranging in relative concentration of nearly 2 orders of magnitude, were positively identified.
View Article and Find Full Text PDFThe hexadehydro-Diels-Alder (HDDA) reaction converts a 1,3-diyne bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates upon thermal activation. With only a few exceptions, this unimolecular cycloisomerization requires, depending on the nature of the atoms connecting the diyne and diynophile, reaction temperatures of 80-130 °C to achieve a convenient half-life (, 1-10 h) for the reaction. In this report, we divulge a new variant of the HDDA process in which the tether contains a central, quaternized nitrogen atom.
View Article and Find Full Text PDFWe have explored the net-[4 + 2]-cycloadditions of a variety of aryl (or alkenyl) alkynes. Tautomerization via base-catalyzed alkyne-to-allene isomerization produces a transient allene, which undergoes stepwise cyclization with not only a pendant alkyne but also a nitrile. The operative mechanisms for these reactions were studied by density functional theory and compared with the slower thermal cyclization of the precursor alkyne.
View Article and Find Full Text PDFTransforming how plastics are made, unmade, and remade through innovative research and diverse partnerships that together foster environmental stewardship is critically important to a sustainable future. Designing, preparing, and implementing polymers derived from renewable resources for a wide range of advanced applications that promote future economic development, energy efficiency, and environmental sustainability are all central to these efforts. In this contribution, we take a comprehensive, integrated approach to summarize important and impactful contributions to this broad research arena.
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