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Sample records for alkyne cycloaddition cuaac

  1. Copper catalysed azide-alkyne cycloaddition (CuAAC) in liquid ammonia.

    PubMed

    Ji, Pengju; Atherton, John H; Page, Michael I

    2012-10-21

    Copper(I) catalysed azide-alkyne cycloaddition reactions (CuAAC) occur smoothly in liquid ammonia (LNH(3)) at room temperature to give exclusively 1,4-substituted 1,2,3-triazoles with excellent yields (up to 99%). The CuAAC reactions in liquid ammonia require relatively small amounts of copper(I) catalyst (0.5 mole%) compared with that in conventional solvents. The product can be obtained conveniently by simply evaporation of ammonia, indicating its potential application in industry. The rate of the CuAAC reaction in liquid ammonia shows a second order dependence on the copper(I) concentration and the reaction occurs only with terminal alkynes. Deuterium exchange experiments with phenyl acetylene-d(1) show that the acidity of the alkyne is increased at least 1000-fold with catalytic amounts of copper(I) in liquid ammonia. The mechanism of the CuAAC reaction in liquid ammonia is discussed. PMID:22930181

  2. Copper-catalysed azide-alkyne cycloadditions (CuAAC): an update.

    PubMed

    Haldón, Estela; Nicasio, M Carmen; Pérez, Pedro J

    2015-10-01

    The reactions of organic azides and alkynes catalysed by copper species represent the prototypical examples of click chemistry. The so-called CuAAC reaction (copper-catalysed azide-alkyne cycloaddition), discovered in 2002, has been expanded since then to become an excellent tool in organic synthesis. In this contribution the recent results described in the literature since 2010 are reviewed, classified according to the nature of the catalyst precursor: copper(I) or copper(II) salts or complexes, metallic or nano-particulated copper and several solid-supported copper systems. PMID:26284434

  3. Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC).

    PubMed

    Mandoli, Alessandro

    2016-01-01

    The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports. PMID:27607998

  4. Blue-light activated rapid polymerization for defect-free bulk Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) crosslinked networks.

    PubMed

    Shete, Abhishek U; El-Zaatari, Bassil M; French, Jonathan M; Kloxin, Christopher J

    2016-08-18

    A visible-light (470 nm wavelength) sensitive Type II photoinitiator system is developed for bulk Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions in crosslinked networks. The accelerated photopolymerization eliminates UV-mediated azide decomposition allowing for the formation of defect-free glassy networks which exhibit a narrow glass transition temperature. PMID:27499057

  5. Kinetics of bulk photo-initiated copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) polymerizations†

    PubMed Central

    Song, Han Byul; Baranek, Austin; Bowman, Christopher N.

    2016-01-01

    Photoinitiation of polymerizations based on the copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction enables spatio-temporal control and the formation of mechanically robust, highly glassy photopolymers. Here, we investigated several critical factors influencing photo-CuAAC polymerization kinetics via systematic variation of reaction conditions such as the physicochemical nature of the monomers; the copper salt and photoinitiator types and concentrations; light intensity; exposure time and solvent content. Real time Fourier transform infrared spectroscopy (FTIR) was used to monitor the polymerization kinetics in situ. Six different di-functional azide monomers and four different tri-functional alkyne monomers containing either aliphatic, aromatic, ether and/or carbamate substituents were synthesized and polymerized. Replacing carbamate structures with ether moieties in the monomers enabled an increase in conversion from 65% to 90% under similar irradiation conditions. The carbamate results in stiffer monomers and higher viscosity mixtures indicating that chain mobility and diffusion are key factors that determine the CuAAC network formation kinetics. Photoinitiation rates were manipulated by altering various aspects of the photo-reduction step; ultimately, a loading above 3 mol% per functional group for both the copper catalyst and the photoinitiator showed little or no rate dependence on concentration while a loading below 3 mol% exhibited 1st order rate dependence. Furthermore, a photoinitiating system consisting of camphorquinone resulted in 60% conversion in the dark after only 1 minute of 75 mW cm−2 light exposure at 400–500 nm, highlighting a unique characteristic of the CuAAC photopolymerization enabled by the combination of the copper(i)’s catalytic lifetime and the nature of the step-growth polymerization. PMID:27429650

  6. Comparative analysis of Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and strain-promoted alkyne-azide cycloaddition (SPAAC) in O-GlcNAc proteomics.

    PubMed

    Li, Shanshan; Zhu, He; Wang, Jiajia; Wang, Xiaomin; Li, Xu; Ma, Cheng; Wen, Liuqing; Yu, Bingchen; Wang, Yuehua; Li, Jing; Wang, Peng George

    2016-06-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an essential protein post-translational modification in a range of organisms. It is involved in various cellular processes such as nutrient sensing, protein degradation, gene expression, and is associated with many human diseases. Despite its importance, identifying O-GlcNAcylated proteins is a major challenge in proteomics. Here, using peracetylated N-azidoacetylglucosamine (Ac4 GlcNAz) as a bioorthogonal chemical handle, we described a gel-based mass spectrometry method for the identification of proteins with O-GlcNAc modification in A549 cells. In addition, we made a labeling efficiency comparison between two modes of azide-alkyne bioorthogonal reactions in click chemistry: copper-catalyzed azide-alkyne cycloaddition (CuAAC) with Biotin-Diazo-Alkyne and stain-promoted azide-alkyne cycloaddition (SPAAC) with Biotin-DIBO-Alkyne. After conjugation with click chemistry in vitro and enrichment via streptavidin resin, proteins with O-GlcNAc modification were separated by SDS-PAGE and identified with mass spectrometry. Proteomics data analysis revealed that 229 putative O-GlcNAc modified proteins were identified with Biotin-Diazo-Alkyne conjugated sample and 188 proteins with Biotin-DIBO-Alkyne conjugated sample, among which 114 proteins were overlapping. Interestingly, 74 proteins identified from Biotin-Diazo-Alkyne conjugates and 46 verified proteins from Biotin-DIBO-Alkyne conjugates could be found in the O-GlcNAc modified proteins database dbOGAP (http://cbsb.lombardi.georgetown.edu/hulab/OGAP.html). These results suggested that CuAAC with Biotin-Diazo-Alkyne represented a more powerful method in proteomics with higher protein identification and better accuracy compared to SPAAC. The proteomics credibility was also confirmed by the molecular function and cell component gene ontology (GO). Together, the method we reported here combining metabolic labeling, click chemistry, affinity-based enrichment, SDS

  7. Au-iClick mirrors the mechanism of copper catalyzed azide–alkyne cycloaddition (CuAAC)

    SciTech Connect

    Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-07-20

    This report outlines the investigation of the iClick mechanism between gold(I)-azides and gold(I)-acetylides to yield digold triazolates. Isolation of digold triazolate complexes offer compelling support for the role of two copper(I) ions in CuAAC. In addition, a kinetic investigation reveals the reaction is first order in both Au(I)-N3 and Au(I)-C≡C-R equivalent to C-R, thus second order overall. A Hammett plot with a ρ = 1.02(5) signifies electron-withdrawing groups accelerate the cycloaddition by facilitating the coordination of the second gold ion in a π-complex. Rate inhibition by the addition of free triphenylphosphine to the reaction indicates that ligand dissociation is a prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.

  8. Au-iClick mirrors the mechanism of copper catalyzed azide–alkyne cycloaddition (CuAAC)

    DOE PAGESBeta

    Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; Veige, Adam S.

    2015-07-20

    This report outlines the investigation of the iClick mechanism between gold(I)-azides and gold(I)-acetylides to yield digold triazolates. Isolation of digold triazolate complexes offer compelling support for the role of two copper(I) ions in CuAAC. In addition, a kinetic investigation reveals the reaction is first order in both Au(I)-N3 and Au(I)-C≡C-R equivalent to C-R, thus second order overall. A Hammett plot with a ρ = 1.02(5) signifies electron-withdrawing groups accelerate the cycloaddition by facilitating the coordination of the second gold ion in a π-complex. Rate inhibition by the addition of free triphenylphosphine to the reaction indicates that ligand dissociation is amore » prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.« less

  9. Copper(I)-catalyzed azide-alkyne cycloaddition for the synthesis of nonlinear electro-optic side-chain copolymers

    NASA Astrophysics Data System (ADS)

    Galindo, Christophe; Soyer, Françoise; Le Barny, Pierre

    2010-10-01

    The Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) has been investigated as a versatile synthetic pathway to graft highly chemically sensitive "push-pull" chromophores onto a polymer backbone. We demonstrate that the CuAAC is highly efficient in mild conditions, chemioselective and is a powerful tool to design new powerful organic NLO side-chain copolymers.

  10. Quick and highly efficient copper-catalyzed cycloaddition of organic azides with terminal alkynes.

    PubMed

    Wang, Dong; Zhao, Mingming; Liu, Xiang; Chen, Yongxin; Li, Na; Chen, Baohua

    2012-01-14

    Good to excellent yields of 1,4-disubstituted 1,2,3-triazoles were obtained within 2-25 min when the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was carried out under solvent-free conditions, with [Cu(phen)(PPh(3))(2)]NO(3) (1mol%) as the catalyst. PMID:22024945

  11. On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition.

    PubMed

    Zhu, Lei; Brassard, Christopher J; Zhang, Xiaoguang; Guha, P M; Clark, Ronald J

    2016-06-01

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4-disubstituted-1,2,3-triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring-formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pKa values and an inclination to engage in π-backbonding with copper(I), azides with ancillary copper-binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne-involved CuAAC reactions are also included, based on the relatively limited data that are available at this point. PMID:27216993

  12. Copper-catalyzed azide alkyne cycloaddition polymer networks

    NASA Astrophysics Data System (ADS)

    Alzahrani, Abeer Ahmed

    The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azide-alkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction. The orthogonally and chemoselectivity of this reaction enable its wide utility across varied scientific fields. Despite numerous inherent advantages and widespread use for small molecule synthesis and solution-based polymer chemistry, it has only recently and rarely been utilized to form polymer networks. This work focuses on the synthesis, mechanisms, and unique attributes of the CuAAC reaction for the fabrication of functional polymer networks. The photo-reduction of a series of copper(II)/amine complexes via ligand metal charge transfer was examined to determine their relative efficiency and selectivity in catalyzing the CuAAC reaction. The aliphatic amine ligands were used as an electron transfer species to reduce Cu(II) upon irradiation with 365 nm light while also functioning as an accelerating agent and as protecting ligands for the Cu(I) that was formed. Among the aliphatic amines studied, tertiary amines such as triethylamine (TEA), tetramethyldiamine (TMDA), N,N,N',N",N"-pentamethyldiethylenetriamine (PMDTA), and hexamethylenetetramine (HMTETA) were found to be the most effective. The reaction kinetics were accelerated by increasing the PMDETA : Cu(II) ratio with a ratio of ligand to Cu(II) of 4:1 yielding the maximum conversion in the shortest time. The sequential and orthogonal nature of the photo

  13. Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

    PubMed Central

    Schöffler, Anne L; Makarem, Ata; Rominger, Frank

    2016-01-01

    Summary A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide–alkyne cycloaddition (CuAAC) “click” reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N-heterocyclic carbene, linker, sacrificial ligand, and counter ion. PMID:27559407

  14. Dinuclear thiazolylidene copper complex as highly active catalyst for azid-alkyne cycloadditions.

    PubMed

    Schöffler, Anne L; Makarem, Ata; Rominger, Frank; Straub, Bernd F

    2016-01-01

    A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide-alkyne cycloaddition (CuAAC) "click" reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N-heterocyclic carbene, linker, sacrificial ligand, and counter ion. PMID:27559407

  15. Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-01-01

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC's catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  16. Highly-Efficient and Versatile Fluorous-Tagged Cu(I)-Catalyzed Azide-Alkyne Cycloaddition Ligand for Preparing Bioconjugates

    PubMed Central

    Sun, Lingyi; Gai, Yongkang; Anderson, Carolyn J.

    2015-01-01

    A novel ligand (FBTTBE) for Cu(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) has been developed, which demonstrates not only superior catalytic efficiency but also the ease of removing toxic copper species. FBTTBE has also been successfully applied in the synthesis of radiometal-labeled peptide and antibody without observable transchelation with the non-radioactive Cu(I) catalyst. PMID:26426419

  17. Highly-efficient and versatile fluorous-tagged Cu(I)-catalyzed azide-alkyne cycloaddition ligand for preparing bioconjugates.

    PubMed

    Sun, Lingyi; Gai, Yongkang; Anderson, Carolyn J; Zeng, Dexing

    2015-12-14

    A novel ligand (FBTTBE) for Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) has been developed, which demonstrates not only superior catalytic efficiency but also the ease of removing toxic copper species. FBTTBE has also been successfully applied in the synthesis of radiometal-labeled peptide and antibody without observable transchelation with the non-radioactive Cu(i) catalyst. PMID:26426419

  18. Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

    PubMed Central

    2013-01-01

    Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  19. Microwave-assisted or Cu-NHC-catalyzed cycloaddition of azido-disubstituted alkynes: bifurcation of reaction pathways.

    PubMed

    Xia, Yuyu; Chen, Ling-yan; Lv, Shang; Sun, Zhihua; Wang, Bing

    2014-10-17

    Microwave irradiation promoted the intramolecular cycloaddition of 2-azidoacetamides derived from α-chiral propargylic amines, affording 1,4,5-trisubstituted triazoles 4 bearing a chiral aminomethyl side chain at C5. In contrast, for the same substrates 3a-k, Cu(I)-NHC complexes catalyzed the intermolecular cycloaddition in an unexpected desilylative fashion, leading to 1,4-disubstituted triazoles 5. This demonstrates that 1-silyl alkynes can be employed as substrates for CuAAC with a suitable coupling partner. PMID:25268332

  20. A highly active and magnetically recoverable tris(triazolyl)-Cu(I) catalyst for alkyne-azide cycloaddition reactions.

    PubMed

    Wang, Dong; Etienne, Laetitia; Echeverria, María; Moya, Sergio; Astruc, Didier

    2014-04-01

    Nanoparticle-supported tris(triazolyl)-CuBr, with a diameter of approximately 25 nm measured by TEM spectroscopy, has been easily prepared, and its catalytic activity was evaluated in the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. In initial experiments, 0.5 mol % loading successfully promoted the CuAAC reaction between benzyl azide and phenylacetylene, in water at room temperature (25 °C). During this process, the iron oxide nanoparticle-supported tris(triazolyl)-CuBr displayed good monodispersity, excellent recoverability, and outstanding reusability. Indeed, it was simply collected and separated from the reaction medium by using an external magnet, then used for another five catalytic cycles without significant loss of catalytic activity. Inductively coupled plasma (ICP) analysis for the first cycle revealed that the amount of copper leached from the catalyst into the reaction medium is negligible (1.5 ppm). The substrate scope has been examined, and it was found that the procedure can be successfully extended to various organic azides and alkynes and can also be applied to the one-pot synthesis of triazoles, through a cascade reaction involving benzyl bromides, alkynes, and sodium azide. In addition, the catalyst was shown to be an efficient CuAAC catalyst for the synthesis of allyl- and TEG-ended (TEG=triethylene glycol) 27-branch dendrimers. PMID:24574335

  1. Accelerating Strain-Promoted Azide-Alkyne Cycloaddition Using Micellar Catalysis.

    PubMed

    Anderton, Grant I; Bangerter, Alyssa S; Davis, Tyson C; Feng, Zhiyuan; Furtak, Aric J; Larsen, Jared O; Scroggin, Triniti L; Heemstra, Jennifer M

    2015-08-19

    Bioorthogonal conjugation reactions such as strain-promoted azide-alkyne cycloaddition (SPAAC) have become increasingly popular in recent years, as they enable site-specific labeling of complex biomolecules. However, despite a number of improvements to cyclooctyne design, reaction rates for SPAAC remain significantly lower than those of the related copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Here we explore micellar catalysis as a means to increase reaction rate between a cyclooctyne and hydrophobic azide. We find that anionic and cationic surfactants provide the most efficient catalysis, with rate enhancements of up to 179-fold for reaction of benzyl azide with DIBAC cyclooctyne. Additionally, we find that the presence of surfactant can provide up to 51-fold selectivity for reaction with a hydrophobic over hydrophilic azide. A more modest, but still substantial, 11-fold rate enhancement is observed for micellar catalysis of the reaction between benzyl azide and a DIBAC-functionalized DNA sequence, demonstrating that micellar catalysis can be successfully applied to hydrophilic biomolecules. Together, these results demonstrate that micellar catalysis can provide higher conjugation yields in reduced time when using hydrophobic SPAAC reagents. PMID:26056848

  2. Rate determination of azide click reactions onto alkyne polymer brush scaffolds: a comparison of conventional and catalyst-free cycloadditions for tunable surface modification.

    PubMed

    Orski, Sara V; Sheppard, Gareth R; Arumugam, Selvanathan; Arnold, Rachelle M; Popik, Vladimir V; Locklin, Jason

    2012-10-16

    The postpolymerization functionalization of poly(N-hydroxysuccinimide 4-vinylbenzoate) brushes with reactive alkynes that differ in relative rates of activity of alkyne-azide cycloaddition reactions is described. The alkyne-derived polymer brushes undergo "click"-type cycloadditions with azido-containing compounds by two mechanisms: a strain-promoted alkyne-azide cycloaddition (SPAAC) with dibenzocyclooctyne (DIBO) and azadibenzocyclooctyne (ADIBO) or a copper-catalyzed alkyne-azide cycloaddition (CuAAC) to a propargyl group (PPG). Using a pseudo-first-order limited rate equation, rate constants for DIBO, ADIBO, and PPG-derivatized polymer brushes functionalized with an azide-functionalized dye were calculated as 7.7 × 10(-4), 4.4 × 10(-3), and 2.0 × 10(-2) s(-1), respectively. The SPAAC click reactions of the surface bound layers were determined to be slower than the equivalent reactions in solution, but the relative ratio of the reaction rates for the DIBO and ADIBO SPAAC reactions was consistent between solution and the polymer layer. The rate of functionalization was not influenced by the diffusion of azide into the polymer scaffold as long as the concentration of azide in solution was sufficiently high. The PPG functionalization by CuAAC had an extremely fast rate, which was comparable to other surface click reaction rates. Preliminary studies of dilute solution azide functionalization indicate that the diffusion-limited regime of brush functionalization impacts a 50 nm polymer brush layer and decreases the pseudo-first-order rate by a constant diffusion-limited factor of 0.233. PMID:23009188

  3. Fluorescent labelling of in situ hybridisation probes through the copper-catalysed azide-alkyne cycloaddition reaction.

    PubMed

    Hesse, Susann; Manetto, Antonio; Cassinelli, Valentina; Fuchs, Jörg; Ma, Lu; Raddaoui, Nada; Houben, Andreas

    2016-09-01

    In situ hybridisation is a powerful tool to investigate the genome and chromosome architecture. Nick translation (NT) is widely used to label DNA probes for fluorescence in situ hybridisation (FISH). However, NT is limited to the use of long double-stranded DNA and does not allow the labelling of single-stranded and short DNA, e.g. oligonucleotides. An alternative technique is the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC), at which azide and alkyne functional groups react in a multistep process catalysed by copper(I) ions to give 1,4-distributed 1,2,3-triazoles at a high yield (also called 'click reaction'). We successfully applied this technique to label short single-stranded DNA probes as well as long PCR-derived double-stranded probes and tested them by FISH on plant chromosomes and nuclei. The hybridisation efficiency of differently labelled probes was compared to those obtained by conventional labelling techniques. We show that copper(I)-catalysed azide-alkyne cycloaddition-labelled probes are reliable tools to detect different types of repetitive sequences on chromosomes opening new promising routes for the detection of single copy gene. Moreover, a combination of FISH using such probes with other techniques, e.g. immunohistochemistry (IHC) and cell proliferation assays using 5-ethynyl-deoxyuridine, is herein shown to be easily feasible. PMID:27095480

  4. Fully Aromatic High Performance Thermoset via Sydnone-Alkyne Cycloaddition.

    PubMed

    Handa, Nisha V; Li, Shaoguang; Gerbec, Jeffrey A; Sumitani, Naoko; Hawker, Craig J; Klinger, Daniel

    2016-05-25

    We have developed an efficient synthetic platform for the preparation of a new class of high performance thermosets based on the 1,3-dipolar cycloaddition of a bifunctional sydnone with a trifunctional alkyne. These processable materials possess outstanding thermal stability, with Td5% of 520 °C and a weight loss of <0.1% per day at 225 °C (both in air). Key to this performance is the stability of the starting functional groups that allows for reactive B-staging via simple thermal activation to give fully aromatic and highly cross-linked polypyrazole-based thermosets. PMID:27180658

  5. Photoinduced Vesicle Formation via the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction.

    PubMed

    Konetski, Danielle; Gong, Tao; Bowman, Christopher N

    2016-08-16

    Synthetic vesicles have a wide range of applications from drug and cosmetic delivery to artificial cell and membrane studies, making simple and controlled formation of vesicles a large focus of the field today. Here, we report the use of the photoinitiated copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction using visible light to introduce spatiotemporal control into the formation of vesicles. Upon the establishment of the spatiotemporal control over vesicle formation, it became possible to adjust initiation conditions to modulate vesicle sizes resulting in the formation of controllably small or large vesicles based on light intensity or giant vesicles when the formation was initiated in flow-free conditions. Additionally, this photoinitiated method enables vesicle formation at a density 400-fold higher than initiation using sodium ascorbate as the catalyst. Together, these advances enable the formation of high-density, controlled size vesicles using low-energy wavelengths while producing enhanced control over the formation characteristics of the vesicle. PMID:27443396

  6. Enantioselective copper-catalyzed azide-alkyne click cycloaddition to desymmetrization of maleimide-based bis(alkynes).

    PubMed

    Song, Tao; Li, Li; Zhou, Wei; Zheng, Zhan-Jiang; Deng, Yuan; Xu, Zheng; Xu, Li-Wen

    2015-01-01

    A copper catalyst system derived from TaoPhos and CuF2 was used successfully for catalytic asymmetric Huisgen [3+2] cycloaddition of azides and alkynes to give optically pure products containing succinimide- and triazole-substituted quaternary carbon stereogenic centers. The desired products were obtained in good yields (60-80 %) and 85:15 to >99:1 enantiomeric ratio (e.r.) in this click cycloaddition reaction. PMID:25388524

  7. Chemo- and Regioselective Rhodium(I)-Catalyzed [2+2+2] Cycloaddition of Allenynes with Alkynes.

    PubMed

    Yasuda, Shigeo; Kawaguchi, Yasuaki; Okamoto, Yuta; Mukai, Chisato

    2016-08-16

    A highly chemo- and regioselective partially intramolecular rhodium(I)-catalyzed [2+2+2] cycloaddition of allenynes with alkynes is described. A range of diverse polysubstituted benzene derivatives could be synthesized in good to excellent yields, in which the allenynes served as synthetic equivalent to the diynes. A high regioselectivity could be observed when allenynes were treated with unsymmetrical alkynes. PMID:27436356

  8. A Concomitant Allylic Azide Rearrangement/Intramolecular Azide–Alkyne Cycloaddition Sequence

    PubMed Central

    2015-01-01

    An intramolecular Huisgen cycloaddition of an interconverting set of isomeric allylic azides with alkynes affords substituted triazoles in high yield. The stereoisomeric vinyl-substituted triazoloxazines formed depend on the rate of cycloaddition of the different allylic azide precursors when the reaction is carried out under thermal conditions. In contrast, dimerized macrocyclic products were obtained when the reaction was done using copper(I)-catalyzed conditions, demonstrating the ability to control the reaction products through changing conditions. PMID:24635056

  9. Copper on Chitosan: A Recyclable Heterogeneous Catalyst for Azide-alkyne Cycloaddition Reactions in Water

    EPA Science Inventory

    Copper sulfate is immobilized over chitosan by simply stirring an aqueous suspension of chitosan in water with copper sulfate; the ensuing catalyst has been utilized for the azide-alkyne cycloaddition in aqueous media and it can be recycled and reused many time without loosing it...

  10. Star-Shaped Polyacrylates: Highly Functionalized Architectures via CuAAC Click Conjugation.

    PubMed

    Lammens, Mieke; Fournier, David; Fijten, Martin W M; Hoogenboom, Richard; Prez, Filip Du

    2009-12-01

    Well-defined functional star-shaped polymer structures with up to 29 arms have been successfully synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. First, azide end-functionalized poly(isobornyl acrylate) (PiBA) star-shaped polymers were prepared by successive ATRP and bromine substitution. Subsequently, alkyne end-functionalized molecules and polymers were introduced onto the star-shaped PiBA bearing pendant azide moieties by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The possibilities and limits for the CuAAC on such highly branched polyacrylates are described. PMID:21638494

  11. Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide-alkyne cycloadditions.

    PubMed

    Worrell, B T; Malik, J A; Fokin, V V

    2013-04-26

    Copper(I)-catalyzed azide-alkyne cycloaddition has become a commonly employed method for the synthesis of complex molecular architectures under challenging conditions. Despite the widespread use of copper-catalyzed cycloaddition reactions, the mechanism of these processes has remained difficult to establish due to the involvement of multiple equilibria between several reactive intermediates. Real-time monitoring of a representative cycloaddition process via heat-flow reaction calorimetry revealed that monomeric copper acetylide complexes are not reactive toward organic azides unless an exogenous copper catalyst is added. Furthermore, crossover experiments with an isotopically enriched exogenous copper source illustrated the stepwise nature of the carbon-nitrogen bond-forming events and the equivalence of the two copper atoms within the cycloaddition steps. PMID:23558174

  12. The Cycloaddition of the Benzimidazolium Ylides with Alkynes: New Mechanistic Insights

    PubMed Central

    Moldoveanu, Costel; Zbancioc, Gheorghita; Mantu, Dorina; Maftei, Dan; Mangalagiu, Ionel

    2016-01-01

    New insights concerning the reaction mechanism in the cycloaddition reaction of benzimidazolium ylides to activated alkynes are presented. The proposed pathway leading both to 2-(1H-pyrrol-1-yl)anilines and to pyrrolo[1,2-a]quinoxalin-4(5H)-ones involves an opening of the imidazole ring from the cycloaddition product, followed by a nucleophilic attack of the aminic nitrogen to a proximal carbonyl group and the elimination of a leaving group. The mechanistic considerations are fully supported by experimental data, including the XRD resolved structure of the key reaction intermediate. PMID:27224656

  13. "Click" Chemistry: Application of Copper Metal in Cu-Catalyzed Azomethine Imine-Alkyne Cycloadditions.

    PubMed

    Pušavec Kirar, Eva; Grošelj, Uroš; Mirri, Giorgio; Požgan, Franc; Strle, Gregor; Štefane, Bogdan; Jovanovski, Vasko; Svete, Jurij

    2016-07-15

    A series of 16 copper-catalyzed azomethine imine-alkyne cycloaddition (CuAIAC) reactions between four pyrazolidinone-1-azomethine imines and four terminal ynones gave the corresponding fluorescent cycloadducts as bimane analogues in very high yields. The applicability of CuAIAC was demonstrated by the fluorescent labeling of functionalized polystyrene and by using Cu-C and Cu-Fe as catalysts. Experimental evidence, kinetic measurements, and correlation between a clean catalyst surface and the reaction rate are in agreement with a homotopic catalytic system with catalytic Cu(I)-acetylide formed from Cu(0) by "in situ" oxidation. The availability of azomethine imines, mild reaction conditions, simple workup, and scalability make CuAIAC a viable supplement to the Cu-catalyzed azide-alkyne cycloaddition reaction in "click" chemistry. PMID:27305104

  14. Investigation of the Pyridinium Ylide--Alkyne Cycloaddition as a Fluorogenic Coupling Reaction.

    PubMed

    Bonte, Simon; Ghinea, Ioana Otilia; Dinica, Rodica; Baussanne, Isabelle; Demeunynck, Martine

    2016-01-01

    The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature. PMID:26978335

  15. Ratiometric Fluorescence Azide-Alkyne Cycloaddition for Live Mammalian Cell Imaging.

    PubMed

    Fu, Hongxia; Li, Yanru; Sun, Lingbo; He, Pan; Duan, Xinrui

    2015-11-17

    Click chemistry with metabolic labeling has been widely used for selectively imaging biomacromolecules in cells. The first example of azide-alkyne cycloaddition for ratiometric fluorescent imaging of live cells is reported. The precursor of the azido fluorophore (cresyl violet) has a fluorescence emission peak at 620 nm. The electron-rich nitrogen of the azido group blue-shifts the emission peak to 566 nm. When the click reaction occurs, an emission peak appears at 620 nm due to the lower electronic density of the newly formed triazole ring, which allows us to ratiometrically record fluorescence signals. This emission shift was applied to ratiometric imaging of propargylcholine- and dibenzocyclooctyne-labeled human breast cancer cells MCF-7 under laser confocal microscopy. Two typical triazole compounds were isolated for photophysical parameter measurements. The emission spectra presented a fluorescence emission peak around 620 nm for both click products. The results further confirmed the emission wavelength change was the result of azide-alkyne cycloaddition reaction. Since nearly all biomolecules can be metabolically labeled by reported alkyne-functionalized derivatives of native metabolites, our method can be readily applied to image these biomacromolecules. PMID:26501208

  16. Metal-Free Intermolecular Azide-Alkyne Cycloaddition Promoted by Glycerol.

    PubMed

    Rodríguez-Rodríguez, Marta; Gras, Emmanuel; Pericàs, Miquel A; Gómez, Montserrat

    2015-12-14

    Metal-free intermolecular Huisgen cycloadditions using nonactivated internal alkynes have been successfully performed in neat glycerol, both under thermal and microwave dielectric heating. In sharp contrast, no reaction occurs in other protic solvents, such as water, ethanol, or diols. DFT calculations have shown that the BnN3/glycerol adduct promotes a more important stabilization of the corresponding LUMO than that produced in the analogous BnN3/alcohol adducts, favoring the reactivity with the alkyne in the first case. The presence of copper salts in the medium did not change the reaction pathway (Cu(I) acts as spectator), except for disubstituted silylalkynes, for which desilylation takes place in contrast to the metal-free system. PMID:26541267

  17. Covalent attachment of diphosphine ligands to glassy carbon electrodes via Cu-catalyzed alkyne-azide cycloaddition. Metallation with Ni(II).

    PubMed

    Das, Atanu K; Engelhard, Mark H; Lense, Sheri; Roberts, John A S; Bullock, R Morris

    2015-07-21

    Covalent tethering of P(Ph)2N(C6H4C≡CH)2 ligands (P(Ph)2N(C6H4C≡CH)2 = 1,5-di-(4-ethynylphenyl)-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane) to planar, azide-terminated glassy carbon electrode surfaces has been accomplished using a Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) coupling reaction, using a BH3←P protection-deprotection strategy. Deprotected, surface-confined ligands were metallated using [Ni(II)(MeCN)6](BF4)2. X-ray photoelectron spectroscopic measurements demonstrate that metallation introduced 1.3 equivalents Ni(II) per diphosphine onto the electrode surface. Exposure of the surface to a second diphosphine ligand, P(Ph)2N(Ph)2, resulted in the removal of Ni from the surface. Protection, coupling, deprotection, and metallation conditions were optimized using solution-phase model systems, with benzyl azide as a model for the azide-terminated carbon surface; these reactions generate a [Ni(II)(diphosphine)2](2+) complex. PMID:25811536

  18. Polymer immobilized Cu(I) formation and azide-alkyne cycloaddition: A one pot reaction

    PubMed Central

    Islam, Rafique Ul; Taher, Abu; Choudhary, Meenakshi; Siwal, Samarjeet; Mallick, Kaushik

    2015-01-01

    During the polymerization of aniline using copper sulphate, act as an oxidizing agent, the in-situ synthesized Cu(I) ion catalyzed the cyclo-addition between azides and alkynes. This work represents the merging of two steps, synthesis of the catalyst and application of the catalyst, in a one pot reaction. The elimination of the separate catalyst synthesis step is economic in terms of cost and time. As aniline was used as one of the reactant components so there is no requirement to use additional base for this reaction that further eliminates the cost of the process. Again, the catalyst can be readily recovered by filtration and efficiently used for the several sets of reactions without any significant loss of catalytic activity. PMID:25966018

  19. Strain-Promoted Alkyne-Azide Cycloadditions (SPAAC) Reveal New Features of Glycoconjugate Biosynthesis

    PubMed Central

    Mbua, Ngalle Eric; Guo, Jun; Wolfert, Margreet A.; Steet, Richard; Boons, Geert-Jan

    2011-01-01

    We have shown that 4-Dibenzocyclooctynol (DIBO), which can easily be obtained by a streamlined synthetic approach, reacts exceptionally fast in the absence of a CuI catalyst with azido-containing compounds to give stable triazoles. Chemical modifications of DIBO, such as oxidation of the alcohol to a ketone, increased the rate of strain promoted azide-alkyne cycloadditions (SPAAC). Installment of a ketone or oxime in the cyclooctyne ring resulted in fluorescent active compounds whereas this property was absent in the corresponding cycloaddition adducts, thereby providing the first example of a metal-free alkyne-azide fluoro-switch click reaction. The alcohol or ketone functions of the cyclooctynes offer a chemical handle to install a variety of different tags, thereby facilitating biological studies. It was found that DIBO modified with biotin combined with metabolic labeling with an azido-containing monosaccharide can determine relative quantities of sialic acid of living cells that have defects in glycosylation (Lec CHO cells). A combined use of metabolic labeling/SPAAC and lectin staining of cells that have defects in the Conserved Oligomeric Golgi (COG) complex revealed that such defects have a greater impact on O-glycan sialylation than galactosylation, whereas sialylation and galactosylation of N-glycans was similarly impacted. These results highlight that the fidelity of Golgi trafficking is a critical parameter for the types of oligosaccharides that are being biosynthesized by a cell. Furthermore, by modulating the quantity of biosynthesized sugar nucleotide, cells may have a means to selectively alter specific glycan structures of glycoproteins. PMID:21661087

  20. The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(I)-Catalyzed Intermolecular Cycloadditions of Vinyl Aziridines and Alkynes.

    PubMed

    Feng, Jian-Jun; Lin, Tao-Yan; Zhu, Chao-Ze; Wang, Huamin; Wu, Hai-Hong; Zhang, Junliang

    2016-02-24

    Catalyst-controlled divergent intermolecular cycloadditions of vinylaziridines with alkynes have been developed. By using [Rh(NBD)2]BF4 as the catalyst, a [3 + 2] cycloaddition reaction was achieved with broad substrate scope and high stereoselectivity under mild reaction conditions. Moreover, the chirality of vinylaziridines can be completely transferred to the [3 + 2] cycloadducts. When the catalyst was changed to [Rh(η(6)-C10H8) (COD)]SbF6, the alternative [5 + 2] cycloadducts were selectively formed under otherwise identical conditions. PMID:26859710

  1. Cycloadditions in modern polymer chemistry.

    PubMed

    Delaittre, Guillaume; Guimard, Nathalie K; Barner-Kowollik, Christopher

    2015-05-19

    Synthetic polymer chemistry has undergone two major developments in the last two decades. About 20 years ago, reversible-deactivation radical polymerization processes started to give access to a wide range of polymeric architectures made from an almost infinite reservoir of functional building blocks. A few years later, the concept of click chemistry revolutionized the way polymer chemists approached synthetic routes. Among the few reactions that could qualify as click, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) initially stood out. Soon, many old and new reactions, including cycloadditions, would further enrich the synthetic macromolecular chemistry toolbox. Whether click or not, cycloadditions are in any case powerful tools for designing polymeric materials in a modular fashion, with a high level of functionality and, sometimes, responsiveness. Here, we wish to describe cycloaddition methodologies that have been reported in the last 10 years in the context of macromolecular engineering, with a focus on those developed in our laboratories. The overarching structure of this Account is based on the three most commonly encountered cycloaddition subclasses in organic and macromolecular chemistry: 1,3-dipolar cycloadditions, (hetero-)Diels-Alder cycloadditions ((H)DAC), and [2+2] cycloadditions. Our goal is to briefly describe the relevant reaction conditions, the advantages and disadvantages, and the realized polymer applications. Furthermore, the orthogonality of most of these reactions is highlighted because it has proven highly beneficial for generating unique, multifunctional polymers in a one-pot reaction. The overview on 1,3-dipolar cycloadditions is mostly centered on the application of CuAAC as the most travelled route, by far. Besides illustrating the capacity of CuAAC to generate complex polymeric architectures, alternative 1,3-dipolar cycloadditions operating without the need for a catalyst are described. In the area of (H)DA cycloadditions

  2. Antifouling coatings based on covalently cross-linked agarose film via thermal azide-alkyne cycloaddition.

    PubMed

    Xu, Li Qun; Pranantyo, Dicky; Neoh, Koon-Gee; Kang, En-Tang; Teo, Serena Lay-Ming; Fu, Guo Dong

    2016-05-01

    Coatings based on thin films of agarose-poly(ethylene glycol) (Agr-PEG) cross-linked systems are developed as environmentally-friendly and fouling-resistant marine coatings. The Agr-PEG cross-linked systems were prepared via thermal azide-alkyne cycloaddition (AAC) using azido-functionalized Agr (AgrAz) and activated alkynyl-containing poly(2-propiolamidoethyl methacrylate-co-poly(ethylene glycol)methyl ether methacrylate) P(PEMA-co-PEGMEMA) random copolymers as the precursors. The Agr-PEG cross-linked systems were further deposited onto a SS surface, pre-functionalized with an alkynyl-containing biomimetic anchor, dopamine propiolamide, to form a thin film after thermal treatment. The thin film-coated SS surfaces can effectively reduce the adhesion of marine algae and the settlement of barnacle cyprids. Upon covalent cross-linking, the covalently cross-linked Agr-PEG films coated SS surfaces exhibit good stability in flowing artificial seawater, and enhanced resistance to the settlement of barnacle cyprids, in comparison to that of the surfaces coated with physically cross-linked AgrAz films. PMID:26836479

  3. The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes

    SciTech Connect

    Malaska, M.J.

    1991-01-01

    The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes was investigated. The cocyclization of 2-propynyloxymethylthiophenes provided two types of cyclohexadiene complexes. It was found that one of these complexes could be converted to the other by a thermal rearrangement. This novel transformation was investigated by deuterium-labelling and kinetic studies, and a mechanism was proposed. The complexes could be oxidatively demetallated to provide the liberated organic framework. Further reorganization of these dienes were observed during the decomplexation process and in the presence of CpCo(C[sub 2]H[sub 4])[sub 2]. In this manner several new heterocyclic ring systems could be constructed from 2-substituted thiophenes. Following the success of the thiophene cyclizations, the cocyclization of the benzofuran nucleus was examined. Reagents and conditions were developed that provide an efficient synthesis of alkynols from carboxylic acids; other functional group interconversions of the alkynols were briefly studied. The synthesis and cyclization of 1-[7-methoxy-4-benzofuranyl]-3-butyn-2-ol produced a cobalt complex containing the A,B,C, and D rings of the morphine skeleton. A synthetic advantage of this methodology would be the ease of substitution at pharmaco-logically relevant C-6 and C-7 positions of the morphine framework. Synthetic routes using a cobalt cyclization strategy were proposed.

  4. Biocompatible Azide-Alkyne "Click" Reactions for Surface Decoration of Glyco-Engineered Cells.

    PubMed

    Gutmann, Marcus; Memmel, Elisabeth; Braun, Alexandra C; Seibel, Jürgen; Meinel, Lorenz; Lühmann, Tessa

    2016-05-01

    Bio-orthogonal copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used to modify azide- or alkyne-bearing monosaccharides on metabolic glyco-engineered mammalian cells. Here, we present a systematic study to elucidate the design space for the cytotoxic effects of the copper catalyst on NIH 3T3 fibroblasts and on HEK 293-F cells. Monitoring membrane integrity by flow cytometry and RT-PCR analysis with apoptotic and anti-apoptotic markers elucidated the general feasibility of CuAAC, with exposure time of the CuAAC reaction mixture having the major influence on biocompatibility. A high labeling efficiency of HEK 293-F cells with a fluorescent alkyne dye was rapidly achieved by CuAAC in comparison to copper free strain-promoted azide-alkyne cycloaddition (SPAAC). The study details effective and biocompatible conditions for CuAAC-based modification of glyco-engineered cells in comparison to its copper free alternative. PMID:26818821

  5. Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties.

    PubMed

    Piluso, Susanna; Hiebl, Bernhard; Gorb, Stanislav N; Kovalev, Alexander; Lendlein, Andreas; Neffe, Axel T

    2011-02-01

    Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper- catalyzed azide-alkyne cycloaddition (known as "click chemistry"). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications. PMID:21374560

  6. Effect of Buffer Conditions and Organic Cosolvents on the Rate of Strain-Promoted Azide-Alkyne Cycloaddition.

    PubMed

    Davis, Derek L; Price, Erin K; Aderibigbe, Sabrina O; Larkin, Maureen X-H; Barlow, Emmett D; Chen, Renjie; Ford, Lincoln C; Gray, Zackery T; Gren, Stephen H; Jin, Yuwei; Keddington, Keith S; Kent, Alexandra D; Kim, Dasom; Lewis, Ashley; Marrouche, Rami S; O'Dair, Mark K; Powell, Daniel R; Scadden, Mick'l H C; Session, Curtis B; Tao, Jifei; Trieu, Janelle; Whiteford, Kristen N; Yuan, Zheng; Yun, Goyeun; Zhu, Judy; Heemstra, Jennifer M

    2016-08-01

    We investigate the effect of buffer identity, ionic strength, pH, and organic cosolvents on the rate of strain-promoted azide-alkyne cycloaddition with the widely used DIBAC cyclooctyne. The rate of reaction between DIBAC and a hydrophilic azide is highly tolerant to changes in buffer conditions but is impacted by organic cosolvents. Thus, bioconjugation reactions using DIBAC can be carried out in the buffer that is most compatible with the biomolecules being labeled, but the use of organic cosolvents should be carefully considered. PMID:27387821

  7. Rhodium-catalyzed Intra- and Intermolecular [5+2] Cycloaddition of 3-Acyloxy-1,4-enyne and Alkyne with Concomitant 1,2-Acyloxy Migration

    PubMed Central

    Shu, Xing-Zhong; Li, Xiaoxun; Shu, Dongxu; Huang, Suyu; Schienebeck, Casi M.; Zhou, Xin; Robichaux, Patrick J.; Tang, Weiping

    2012-01-01

    A new type of rhodium-catalyzed [5+2] cycloaddition was developed for the synthesis of seven-membered rings with diverse functionalities. The ring formation was accompanied by a 1,2-acyloxy migration event. The 5- and 2-carbon components of the cycloaddition are 3-acyloxy-1,4-enynes (ACEs) and alkynes respectively. Cationic rhodium (I) catalysts worked most efficiently for the intramolecular cycloaddition, while only neutral rhodium (I) complexes could facilitate the intermolecular reaction. In both cases, electron-poor phosphite or phosphine ligands often improved the efficiency of the cycloadditions. The scope of ACEs and alkynes was investigated in both intra- and intermolecular reactions. The resulting seven-membered ring products have three double bonds that could be selectively functionalized. PMID:22364320

  8. Rhodium-Catalyzed Intramolecular [5+2] Cycloaddition of Inverted 3-Acyloxy-1,4-enyne and Alkyne: Experimental and Theoretical Studies.

    PubMed

    Li, Xiaoxun; Song, Wangze; Ke, Xiaona; Xu, Xiufang; Liu, Peng; Houk, K N; Zhao, Xian-Liang; Tang, Weiping

    2016-05-17

    By switching the position of the alkene and alkyne, a new type of 3-acyloxy-1,4-enyne (ACE) five-carbon building block was developed for Rh-catalyzed intramolecular [5+2] cycloaddition. An electron-withdrawing acyl group on the alkyne termini of the ACE was essential for a regioselective 1,2-acyloxy migration. This new method provided bicyclic [5.3.0]decatrienes that are different from previous methods because of the positions of the alkenes and the acyloxy group. Multiple mechanistic pathways become possible for this new [5+2] cycloaddition and they are investigated by computational studies. PMID:26990319

  9. A solid-phase CuAAC strategy for the synthesis of PNA containing nucleobase surrogates

    PubMed Central

    St. Amant, André H.; Engbers, Christopher; Hudson, Robert H.E.

    2013-01-01

    The synthesis of an azide containing PNA monomer is described. The monomer was incorporated into two PNA sequences for the purpose of synthesizing an intercalating fluorophore-labeled PNA and a metal binding hairpin using a solid phase copper catalyzed azide-alkyne Huisgen cycloaddition (CuAAC). Click chemistry was performed using 2-ethynylfluorene or 1-ethynylpyrene to add a fluorophore to the PNA, which were tested for their ability to recognize an abasic site on a DNA target. A PNA hairpin possessing azide monomers at each termini was synthesized and reacted with 2-ethynylpyridine to form a hairpin that is stabilized by Ni2+. PMID:23422048

  10. [5+2] Cycloaddition of 2-(2-Aminoethyl)oxiranes with Alkynes via Epoxide Ring-Opening: A Facile Access to Azepines.

    PubMed

    Hu, Chao; Song, Ren-Jie; Hu, Ming; Yang, Yuan; Li, Jin-Heng; Luo, Shenglian

    2016-08-22

    A new FeCl3 and BF3 ⋅OEt2 co-catalyzed tandem hetero-[5+2] cycloaddition of 2-(2-aminoethyl)oxiranes with a wide range of alkynes, including terminal alkynes and alkyl-substituted internal alkynes is presented. This is the first example of rapid and facile production of diverse 2,3-dihydro-1H-azepines through a sequence of epoxide ring-opening, annulation, and dehydroxylation with broad substrate scope and exquisite selectivity control. PMID:27457771

  11. CuAAC click reactions for the design of multifunctional luminescent ruthenium complexes.

    PubMed

    Zabarska, Natalia; Stumper, Anne; Rau, Sven

    2016-02-01

    CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed. PMID:26758682

  12. 1,2,3-Triazoles from carbonyl azides and alkynes: filling the gap.

    PubMed

    Haldón, Estela; Álvarez, Eleuterio; Nicasio, M Carmen; Pérez, Pedro J

    2014-08-18

    Electron deficient azides are challenging substrates in CuAAC reactions. Particularly, when N-carbonyl azides are applied the formation of N-carbonyl triazoles has not yet been observed. We report herein the first example of this class of reaction, with a copper-based system that efficiently enables the synthesis of N-carbamoyl 1,2,3-triazoles by [3+2] cycloaddition of N-carbamoyl azides and alkynes. PMID:24980244

  13. Three-component synthesis of neoglycopeptides using a Cu(II)-triggered aminolysis of peptide hydrazide resin and an azide-alkyne cycloaddition sequence.

    PubMed

    Ebran, Jean-Philippe; Dendane, Nabil; Melnyk, Oleg

    2011-08-19

    Copper(II)-induced oxidative aminolysis of hydrazides generates Cu(I), the catalyst of the azide-alkyne cycloaddition. This feature was exploited to design a novel solid phase detaching three-component reaction permitting the conversion of supported peptide hydrazides into 1,2,3-triazole linked C-terminal neoglycopeptides. PMID:21766830

  14. Transition-Metal-Catalyzed Bioorthogonal Cycloaddition Reactions.

    PubMed

    Yang, Maiyun; Yang, Yi; Chen, Peng R

    2016-02-01

    In recent years, bioorthogonal reactions have emerged as a powerful toolbox for specific labeling and visualization of biomolecules, even within the highly complex and fragile living systems. Among them, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is one of the most widely studied and used biocompatible reactions. The cytotoxicity of Cu(I) ions has been greatly reduced due to the use of Cu(I) ligands, which enabled the CuAAC reaction to proceed on the cell surface, as well as within an intracellular environment. Meanwhile, other transition metals such as ruthenium, rhodium and silver are now under development as alternative sources for catalyzing bioorthogonal cycloadditions. In this review, we summarize the development of CuAAC reaction as a prominent bioorthogonal reaction, discuss various ligands used in reducing Cu(I) toxicity while promoting the reaction rate, and illustrate some of its important biological applications. The development of additional transition metals in catalyzing cycloaddition reactions will also be briefly introduced. PMID:27572985

  15. Carbohydrate CuAAC click chemistry for therapy and diagnosis.

    PubMed

    He, Xiao-Peng; Zeng, Ya-Li; Zang, Yi; Li, Jia; Field, Robert A; Chen, Guo-Rong

    2016-06-24

    Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development. PMID:27085906

  16. Regioselective Synthesis of C-3-Functionalized Quinolines via Hetero-Diels-Alder Cycloaddition of Azadienes with Terminal Alkynes.

    PubMed

    Saunthwal, Rakesh K; Patel, Monika; Verma, Akhilesh K

    2016-08-01

    A highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines from azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes through [4 + 2] cycloaddition has been developed. An unprecedented reaction of 2-aminobenzyl alcohol with 1,3- and 1,4-diethynylbenzene provided the C-3 tolylquinolines via [4 + 2] HDA and oxidative decarboxylation. The -NH2 group directed mechanistic approach was well supported by the control experiments and deuterium-labeling studies and by isolating the azadiene intermediate. The reactivity and selectivity of unprotected azadiene in metal-free base-assisted hetero-Diels-Alder reaction is exploited to quickly assemble an important class of C-3-functionalized quinolines, which are difficult to access. PMID:27380814

  17. Experimental investigation on the mechanism of chelation-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition.

    PubMed

    Kuang, Gui-Chao; Guha, Pampa M; Brotherton, Wendy S; Simmons, J Tyler; Stankee, Lisa A; Nguyen, Brian T; Clark, Ronald J; Zhu, Lei

    2011-09-01

    A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)(2)) in copper(II)-mediated azide-alkyne cycloaddition (AAC) reactions. Fluorescence and (1)H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)(2) suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)(2) in

  18. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold.

    PubMed

    Werkhoven, Paul R; van de Langemheen, Helmus; van der Wal, Steffen; Kruijtzer, John A W; Liskamp, Rob M J

    2014-04-01

    Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile convergent strategy for the construction of protein mimics presenting three different cyclic peptides. Using an orthogonal alkyne protection strategy, peptide loops were introduced successively onto a triazacyclophane scaffold via Cu(I)-catalyzed azide alkyne cycloaddition. This method provides rapid access to protein mimics requiring different peptide segments for their interaction and activity. PMID:24599619

  19. Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

    PubMed Central

    Filichev, Vyacheslav V; Boutorine, Alexandre S

    2016-01-01

    Summary Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs. PMID:27559384

  20. Copper(I)-catalyzed azide-alkyne cycloadditions in microflow: catalyst activity, high-T operation, and an integrated continuous copper scavenging unit.

    PubMed

    Varas, Alvaro Carlos; Noël, Timothy; Wang, Qi; Hessel, Volker

    2012-09-01

    AVOIDING THE COPPERS: A continuous-flow synthesis for the Cu(I) -catalyzed azide-alkyne cycloaddition reaction using [Cu(phenanthroline)(PPh₃)₂]NO₃ as a homogeneous catalyst is developed (up to 92 % isolated yield). Elevated temperatures allow achieving full conversions and using lower catalyst loadings. Residual copper in the triazole compound is efficiently removed via an inline extraction process, employing aqueous EDTA as a copper scavenger. PMID:22753337

  1. Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.

    PubMed

    Gill, Herman S; Marik, Jan

    2011-11-01

    An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min. PMID:22011654

  2. Alkyne-azide cycloaddition catalyzed by silver chloride and "abnormal" silver N-heterocyclic carbene complex.

    PubMed

    Ortega-Arizmendi, Aldo I; Aldeco-Pérez, Eugenia; Cuevas-Yañez, Erick

    2013-01-01

    A library of 1,2,3-triazoles was synthesized from diverse alkynes and azides using catalytic amounts of silver chloride instead of copper compounds. In addition, a novel "abnormal" silver N-heterocyclic carbene complex was tested as catalyst in this process. The results suggest that the reaction requires only 0.5% of silver complex, affording 1,2,3-triazoles in good yields. PMID:24307866

  3. Direct Evidence for a [4+2] Cycloaddition Mechanism of Alkynes to Tantallacyclopentadiene on Dinuclear Tantalum Complexes as a Model of Alkyne Cyclotrimerization.

    PubMed

    Yamamoto, Keishi; Tsurugi, Hayato; Mashima, Kazushi

    2015-08-01

    A dinuclear tantalum complex, [Ta2 Cl6 (μ-C4 Et4)] (2), bearing a tantallacyclopentadiene moiety, was synthesized by treating [(η(2) -EtC≡CEt)TaCl3 (DME)] (1) with AlCl3 . Complex 2 and its Lewis base adducts, [Ta2 Cl6 (μ-C4 Et4 )L] (L=THF (3 a), pyridine (3 b), THT (3 c)), served as more active catalysts for cyclotrimerization of internal alkynes than 1. During the reaction of 3 a with 3-hexyne, we isolated [Ta2 Cl4 (μ-η(4):η(4)-C6 Et6)(μ-η(2):η(2)-EtC≡CEt)] (4), sandwiched by a two-electron reduced μ-η(4):η(4) -hexaethylbenzene and a μ-η(2):η(2)-3-hexyne ligand, as a product of an intermolecular cyclization between the metallacyclopentadiene moiety and 3-hexyne. The formation of arene complexes [Ta2 Cl4 (μ-η(4):η(4)-C6 Et4 Me2)(μ-η(2):η(2)-Me3 SiC≡CSiMe3)] (7 b) and [Ta2 Cl4 (μ-η(4):η(4)-C6 Et4 RH)(μ-η(2):η(2)-Me3 SiC≡CSiMe3)] (R=nBu (8 a), p-tolyl (8 b)) by treating [Ta2 Cl4 (μ-C4 Et4)(μ-η(2):η(2) -Me3 SiC≡CSiMe3)] (6) with 2-butyne, 1-hexyne, and p-tolylacetylene without any isomers, at room temperature or low temperature were key for clarifying the [4+2] cycloaddition mechanism because of the restricted rotation behavior of the two-electron reduced arene ligands without dissociation from the dinuclear tantalum center. PMID:26118787

  4. Triphenylene discotic liquid crystal trimers synthesized by Co2(CO)8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

    PubMed Central

    Han, Bin; Hu, Ping; Wang, Bi-Qin; Redshaw, Carl

    2013-01-01

    Summary The synthesis of star-shaped discotic liquid crystal trimers using Co2(CO)8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition reaction is reported. The trimers consist of three triphenylene discotic units linked to a central 1,2,4-trisubstituted benzene ring via flexible spacers. The trimers were synthesized in the yields up to 70% by mixing the monomers with 10 mol % of Co2(CO)8 as the catalyst in refluxing 1,4-dioxane. The liquid crystalline properties were investigated by using polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Trimer 4 with an ester connecting group and a longer spacer exhibited a rectangular columnar mesophase, while 5b and 5c possessing an ether linkage and a shorter spacer display a hexagonal columnar mesophase. The connecting functional group and the length of the flexible spacer between the central benzene ring and the triphenylene units have pivotal influence on the mesomorphism. PMID:24367450

  5. A sequential Ugi multicomponent/Cu-catalyzed azide-alkyne cycloaddition approach for the continuous flow generation of cyclic peptoids.

    PubMed

    Salvador, Carlos Eduardo M; Pieber, Bartholomäus; Neu, Philipp M; Torvisco, Ana; Kleber Z Andrade, Carlos; Kappe, C Oliver

    2015-05-01

    The development of a continuous flow multistep strategy for the synthesis of linear peptoids and their subsequent macrocyclization via Click chemistry is described. The central transformation of this process is an Ugi four-component reaction generating the peptidomimetic core structure. In order to avoid exposure to the often toxic and malodorous isocyanide building blocks, the continuous approach was telescoped by the dehydration of the corresponding formamide. In a concurrent operation, the highly energetic azide moiety required for the subsequent intramolecular copper-catalyzed azide-alkyne cycloaddition (Click reaction) was installed by nucleophilic substitution from a bromide precursor. All steps yielding to the linear core structures can be conveniently coupled without the need for purification steps resulting in a single process generating the desired peptidomimetics in good to excellent yields within a 25 min reaction time. The following macrocyclization was realized in a coil reactor made of copper without any additional additive. A careful process intensification study demonstrated that this transformation occurs quantitatively within 25 min at 140 °C. Depending on the resulting ring strain, either a dimeric or a monomeric form of the cyclic product was obtained. PMID:25842982

  6. Utilizing copper(I) catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition for the surface modification of colloidal particles with electroactive and emissive moieties

    NASA Astrophysics Data System (ADS)

    Rungta, Parul

    " chemistry; Aqueous-phase 83 nm poly(propargyl acrylate) (PA) nanoparticles were surface-functionalized with sparingly water soluble fluorescent moieties through a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) (i.e., "click" transformation) to produce fluoroprobes with a large Stokes shift. For moieties which could not achieve extensive surface coverage on the particles utilizing a standard click transformation procedure, the presence of beta-cyclodextrin (beta-CD) during the transformation enhanced the grafting density onto the particles. For an oxadiazole containing molecule (AO), an azide-modified coumarin 6 (AD1) and a polyethylene glycol modified naphthalimide-based emitter (AD2), respectively, an 84%, 17% and 5% increase in the grafting densities were observed, when the transformation was performed in the presence of beta-CD. In contrast, a carbazolyl-containing moiety (AC) exhibited a slight retardation in the final grafting density when beta-CD was employed. Photoluminescence studies indicated that AC & AO when attached to the particles form an exciplex. An efficient energy transfer from the exciplex to the surface attached AD2 resulted in a total Stokes shift of 180 nm for the modified particles. (3) The synthesis and characterization of near-infrared (NIR) emitting particles for potential applications in cancer therapy. PA particles were surface modified through the "click" transformation of an azide-terminated indocyanine green (azICG), an NIR emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin (BSA) when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic nine-fold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response

  7. Simultaneous Photoinduced ATRP and CuAAC Reactions for the Synthesis of Block Copolymers.

    PubMed

    Murtezi, Eljesa; Yagci, Yusuf

    2014-09-01

    Atom transfer radical polymerization (ATRP) and copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions, both utilizing copper(I) (Cu(I)) complexes, make a tremendous progress in synthetic polymer chemistry. Independently or in combination with other polymerization processes, they give access to the synthesis of polymers with well-defined structures, desired molecular architectures, and a wide variety of functionalities. Here, a novel in situ photoinduced formation of block copolymers is described by simultaneous ATRP and CuAAC processes. This approach relies on the direct reduction of initially charged copper(II) complexes to Cu(I) complexes to trigger both ATRP and CuAAC reactions coinciding under UV light at ambient temperature in one pot. Its synthetic utility is demonstrated on a model block copolymerization process by photoinduced ATRP of methyl methacrylate (MMA) using an initiator possessing acetylene functionality and concomitant click reaction between thus formed α-acetylene-poly(methyl methacrylate) (Ac-PMMA) and independently prepared azide functional polystyrene (PS-N3 ). Successful formation of PS-b-PMMA block copolymer is confirmed by FT-IR and (1) H NMR spectral analysis and gel permeation chromatography (GPC) measurements. PMID:25200624

  8. Enantioselective rhodium-catalyzed [2 + 2 + 2] cycloadditions of terminal alkynes and alkenyl isocyanates: mechanistic insights lead to a unified model that rationalizes product selectivity.

    PubMed

    Dalton, Derek M; Oberg, Kevin M; Yu, Robert T; Lee, Ernest E; Perreault, Stéphane; Oinen, Mark Emil; Pease, Melissa L; Malik, Guillaume; Rovis, Tomislav

    2009-11-01

    This manuscript describes the development and scope of the asymmetric rhodium-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes and alkenyl isocyanates leading to the formation of indolizidine and quinolizidine scaffolds. The use of phosphoramidite ligands proved crucial for avoiding competitive terminal alkyne dimerization. Both aliphatic and aromatic terminal alkynes participate well, with product selectivity a function of both the steric and electronic character of the alkyne. Manipulation of the phosphoramidite ligand leads to tuning of enantio- and product selectivity, with a complete turnover in product selectivity seen with aliphatic alkynes when moving from Taddol-based to biphenol-based phosphoramidites. Terminal and 1,1-disubstituted olefins are tolerated with nearly equal efficacy. Examination of a series of competition experiments in combination with analysis of reaction outcome shed considerable light on the operative catalytic cycle. Through a detailed study of a series of X-ray structures of rhodium(cod)chloride/phosphoramidite complexes, we have formulated a mechanistic hypothesis that rationalizes the observed product selectivity. PMID:19817441

  9. Enantioselective Rhodium-Catalyzed [2+2+2] Cycloadditions of Terminal Alkynes and Alkenyl Isocyanates: Mechanistic Insights Lead to a Unified Model that Rationalizes Product Selectivity

    PubMed Central

    Dalton, Derek M.; Oberg, Kevin M.; Yu, Robert T.; Lee, Ernest E.; Perreault, Stéphane; Oinen, Mark Emil; Pease, Melissa L.; Malik, Guillaume; Rovis, Tomislav

    2009-01-01

    This manuscript describes the development and scope of the asymmetric rhodium-catalyzed [2+2+2] cycloaddition of terminal alkynes and alkenyl isocyanates leading to the formation of indolizidine and quinolizidine scaffolds. The use of phosphoramidite ligands proved crucial for avoiding competitive terminal alkyne dimerization. Both aliphatic and aromatic terminal alkynes participate well, with product selectivity a function of both the steric and electronic character of the alkyne. Manipulation of the phosphoramidite ligand leads to tuning of enantio- and product selectivity, with a complete turnover in product selectivity seen with aliphatic alkynes when moving from Taddol-based to biphenol-based phosphoramidites. Terminal and 1,1-disubstituted olefins are tolerated with nearly equal efficacy. Examination of a series of competition experiments in combination with analysis of reaction outcome shed considerable light on the operative catalytic cycle. Through a detailed study of a series of X-ray structures of rhodium(cod)chloride/phosphoramidite complexes, we have formulated a mechanistic hypothesis that rationalizes the observed product selectivity. PMID:19817441

  10. Rapid screening of copper intermediates in Cu(i)-catalyzed azide-alkyne cycloaddition using a modified ICP-MS/MS platform.

    PubMed

    He, Qian; Xing, Zhi; Wei, Chao; Fang, Xiang; Zhang, Sichun; Zhang, Xinrong

    2016-08-18

    Rapid screening of Cu(+)-intermediates by using (63)Cu(+) or (65)Cu(+) ions as catalysts with or without ligand protection in Cu(i)-catalyzed azide-alkyne cycloaddition was realized using an on-line modified ICP-MS/MS platform in this work, while the Cu(+)-intermediates without ligand protection are very active, which are extremely difficult to be observed using other existing techniques. This universal platform was suitable to study the mechanism of organic reactions catalyzed by unstable metal(i) ions as well as to discover new candidates for metal(i) catalysts. PMID:27487942

  11. Competing Mechanisms, Substituent Effects, and Regioselectivities of Nickel-Catalyzed [2 + 2 + 2] Cycloaddition between Carboryne and Alkynes: A DFT Study.

    PubMed

    Mu, Wei-Hua; Xia, Shu-Ya; Li, Ji-Xiang; Fang, De-Cai; Wei, Gang; Chass, Gregory A

    2015-09-18

    Competing reaction mechanisms, substituent effects, and regioselectivities of Ni(PPh3)2-catalyzed [2 + 2 + 2] carboryne-alkyne cycloadditions were characterized by density functional theory using the real chemical systems and solvent effects considered. A putative mechanism involving the following steps was characterized: (1) exothermic carboryne-catalyst complexation and nucleophilic attack by the first alkyne; (2) insertion of the second alkyne, the rate-determining step (RDS) in all four reactions studied; (3) isomerization of reactant-bound complexes; and (4) product elimination and catalyst regeneration. The RDS in three reactions is mediated by free energy barriers of 27.2, 31.1, and 36.6 kcal·mol(-1), representative of the corresponding experimental yields of 67, 54, and 33%, respectively. A fourth reaction with 0% experimental yield showed representative RDS free energy barriers of 60.4 kcal·mol(-1), which are difficult to surmount even at 90 °C. Alternative pathways leading to differing isomers were similarly characterized and successfully reproduced experimentally determined product regioselectivities. Kinetic data derived from free energy barriers are in quantitative agreement (< ± 0.75-3.0 kcal·mol(-1)) of the experimental times, affirming the theoretical results as representative of the real chemical transformations. Complementary determinations show the use of truncated models (Ni(PMe3)2, Ni(PH3)2) causes the RDS to vary from step 2 (alkyne insertion) to step 1 (alkyne attack), highlighting the need to employ real chemical systems in modeling these reactions. PMID:26270257

  12. Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

    ERIC Educational Resources Information Center

    Mendes, Desiree E.; Schoffstall, Allen M.

    2011-01-01

    This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

  13. Synthesis of Porphyrin, Chlorin and Phthalocyanine Derivatives by Azide-Alkyne Click Chemistry.

    PubMed

    Acherar, Samir; Colombeau, Ludovic; Frochot, Céline; Vanderesse, Régis

    2015-01-01

    The aim of this review is to provide a summary of the use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) in the synthesis of porphyrin, chlorin and phthalocyanine derivatives for different types of therapeutic applications. The click reaction is a powerful and versatile tool for scientists working on the synthesis of various symmetrically and asymmetrically substituted tetrapyrrolic derivatives. For example, click chemistry is widely used for the elaboration of photosensitizer conjugates for photodynamic therapy applications. Other biological applications are also described. PMID:26179994

  14. Utilizing copper(I) catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition for the surface modification of colloidal particles with electroactive and emissive moieties

    NASA Astrophysics Data System (ADS)

    Rungta, Parul

    " chemistry; Aqueous-phase 83 nm poly(propargyl acrylate) (PA) nanoparticles were surface-functionalized with sparingly water soluble fluorescent moieties through a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) (i.e., "click" transformation) to produce fluoroprobes with a large Stokes shift. For moieties which could not achieve extensive surface coverage on the particles utilizing a standard click transformation procedure, the presence of beta-cyclodextrin (beta-CD) during the transformation enhanced the grafting density onto the particles. For an oxadiazole containing molecule (AO), an azide-modified coumarin 6 (AD1) and a polyethylene glycol modified naphthalimide-based emitter (AD2), respectively, an 84%, 17% and 5% increase in the grafting densities were observed, when the transformation was performed in the presence of beta-CD. In contrast, a carbazolyl-containing moiety (AC) exhibited a slight retardation in the final grafting density when beta-CD was employed. Photoluminescence studies indicated that AC & AO when attached to the particles form an exciplex. An efficient energy transfer from the exciplex to the surface attached AD2 resulted in a total Stokes shift of 180 nm for the modified particles. (3) The synthesis and characterization of near-infrared (NIR) emitting particles for potential applications in cancer therapy. PA particles were surface modified through the "click" transformation of an azide-terminated indocyanine green (azICG), an NIR emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin (BSA) when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic nine-fold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response

  15. Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

    PubMed Central

    Bharathimohan, Kuppusamy; Ponpandian, Thanasekaran; Bhuvanesh, Nattamai

    2014-01-01

    Summary Herein, we describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This methodology is more convenient to produce the complex polycyclic molecules in a simple way. PMID:25670973

  16. Sequential decarboxylative azide-alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles.

    PubMed

    Bharathimohan, Kuppusamy; Ponpandian, Thanasekaran; Ahamed, A Jafar; Bhuvanesh, Nattamai

    2014-01-01

    Herein, we describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This methodology is more convenient to produce the complex polycyclic molecules in a simple way. PMID:25670973

  17. Synthesis of steroid-ferrocene conjugates of steroidal 17-carboxamides via a palladium-catalyzed aminocarbonylation--copper-catalyzed azide-alkyne cycloaddition reaction sequence.

    PubMed

    Szánti-Pintér, Eszter; Balogh, János; Csók, Zsolt; Kollár, László; Gömöry, Agnes; Skoda-Földes, Rita

    2011-11-01

    Steroids with the 17-iodo-16-ene functionality were converted to ferrocene labeled steroidal 17-carboxamides via a two step reaction sequence. The first step involved the palladium-catalyzed aminocarbonylation of the alkenyl iodides with prop-2-yn-1-amine as the nucleophile in the presence of the Pd(OAc)(2)/PPh(3) catalyst system. In the second step, the product N-(prop-2-ynyl)-carboxamides underwent a facile azide-alkyne cycloaddition with ferrocenyl azides in the presence of CuSO(4)/sodium ascorbate to produce the steroid-ferrocene conjugates. The new compounds were obtained in good yield and were characterized by (1)H and (13)C NMR, IR, MS and elemental analysis. PMID:21787798

  18. 18F-Labeling Using Click Cycloadditions

    PubMed Central

    Ross, Tobias L.

    2014-01-01

    Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. PMID:25003110

  19. The use of azide-alkyne click chemistry in recent syntheses and applications of polytriazole-based nanostructured polymers

    NASA Astrophysics Data System (ADS)

    Shi, Yi; Cao, Xiaosong; Gao, Haifeng

    2016-02-01

    The rapid development of efficient organic click coupling reactions has significantly facilitated the construction of synthetic polymers with sophisticated branched nanostructures. This Feature Article summarizes the recent progress in the application of efficient copper-catalyzed and copper-free azide-alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star polymers, graft polymers, molecular brushes, and cyclic graft polymers. Literature reports on the interesting properties and functions of these polytriazole-based nanostructured polymers are also discussed to illustrate their potential applications as self-healing polymers, adhesives, polymer catalysts, opto-electronic polymer materials and polymer carriers for drug and imaging molecules.

  20. Cysteine as a Monothiol Reducing Agent to Prevent Copper-Mediated Oxidation of Interferon Beta During PEGylation by CuAAC.

    PubMed

    Nairn, Natalie W; Bariola, Pauline A; Graddis, Thomas J; VanBrunt, Michael Pete; Wang, Aijun; Li, Gary; Grabstein, Kenneth

    2015-10-21

    Bioconjugation by copper-catalyzed azide-alkyne cycloaddition (CuAAC) provides a powerful means to produce site-specifically modified proteins. However, the use of a copper catalyst brings about the possible generation of reactive oxygen species that could cause degradation of vulnerable amino acid residues. We investigated whether PEGylation by CuAAC caused any modifications to the therapeutic protein interferon beta-1b, which was produced via global amino acid substitution with azidohomo-alanine at the N-terminus and contains no methionine residues. Using previously reported reaction conditions, LC-MS peptide mapping detected +32 Da and +48 Da oxidation modifications of tryptic peptides 28-33 (LEYCLK) and 137-147 (EYSHCAWTIVR) in the protein post-PEGylation. The oxidative degradation increased with reaction time, whereas reducing the copper concentration slowed the PEGylation rate as well as the oxidation rate. Replacing dithiothreitol (DTT) with any of five different monothiol reducing agents in anaerobic conditions allowed efficient PEGylation in 2-4 h and abrogated oxidative degradation. Free cysteine provided reproducible reaction results as a reducing agent in this system and has been successfully applied to other protein conjugations. Monothiol reducing agents, such as cysteine, may be useful tools as protective reducing agents for CuAAC in some bioconjugation systems. PMID:26439457

  1. [2 + 2 + 2]Cycloadditions of alkynes to furans and thiophenes. A cobalt-mediated [open quotes]enol ether walk[close quotes

    SciTech Connect

    Boese, R. ); Harvey, D.F.; Malaska, M.J.; Vollhardt, K.P.C. )

    1994-11-30

    Involvement of the 2,3-double bond of furan and thiophene in cycloadditions is relatively uncommon, usually limited to specific substrates or by special conditions. Our finding that indoles, pyrroles, imidazoles, and uracils can be activated by CpCo to undergo cocyclizations with alkynes suggested an extension of these efforts to the title heterocycles, in particular because the latter constitute new brackets for the degree of aromaticity (furan lowest, thiophene highest) that is subject to neutralization in these reactions and because the anticipated enol (thio)ether products exhibit potential synthetic utility. This study demonstrates that the cobalt-mediated [2 + 2 + 2] methodology can be extended to furans and thiophenes but that in these, and possibly generally in related heteroalkenes, the generation of potential dienylic leaving groups in the resulting CpCo diene product may cause rearrangements and that formal C-H activations may complicate the outcome of the reaction. The observation that the relatively highly aromatic thiophene nucleus functions as a cocyclization partner points the way to a number of even more challenging substrates in this process. 20 refs.

  2. Steering the azido-tetrazole equilibrium of 4-azidopyrimidines via substituent variation - implications for drug design and azide-alkyne cycloadditions.

    PubMed

    Thomann, A; Zapp, J; Hutter, M; Empting, M; Hartmann, R W

    2015-11-21

    This paper focuses on an interesting constitutional isomerism called azido-tetrazole equilibrium which is observed in azido-substituted N-heterocycles. We present a systematic investigation of substituent effects on the isomer ratio within a 2-substituted 4-azidopyrimidine model scaffold. NMR- and IR-spectroscopy as well as X-ray crystallography were employed for thorough analysis and characterization of synthesized derivatives. On the basis of this data, we demonstrate the possibility to steer this valence tautomerism towards the isomer of choice by means of substituent variation. We show that the tetrazole form can act as an efficient disguise for the corresponding azido group masking its well known reactivity in azide-alkyne cycloadditions (ACCs). In copper(I)-catalyzed AAC reactions, substituent-stabilized tetrazoles displayed a highly decreased or even abolished reactivity whereas azides and compounds in the equilibrium were directly converted. By use of an acid sensitive derivative, we provide, to our knowledge, the first experimental basis for a possible exploitation of this dynamic isomerism as a pH-dependent azide-protecting motif for selective SPAAC conjugations in aqueous media. Finally, we demonstrate the applicability and efficiency of stabilized tetrazolo[1,5-c]pyrimidines for Fragment-Based Drug Design (FBDD) in the field of quorum sensing inhibitors. PMID:26340222

  3. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

    PubMed Central

    Wang, Ding; Xu, Zheng

    2015-01-01

    Summary The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted. PMID:26734102

  4. Nucleoside azide-alkyne cycloaddition reactions under solvothermal conditions or using copper vials in a ball mill.

    PubMed

    Cummings, Andrew J; Ravalico, Francesco; McColgan-Bannon, Kegan I S; Eguaogie, Olga; Elliott, P Alain; Shannon, Matthew R; Bermejo, Iris A; Dwyer, Angus; Maginty, Amanda B; Mack, James; Vyle, Joseph S

    2015-01-01

    Novel nucleoside analogues containing photoswitchable moieties were prepared using 'click' cycloaddition reactions between 5'-azido-5'-deoxythymidine and mono- or bis-N-propargylamide-substituted azobenzenes. In solution, high to quantitative yields were achieved using 5 mol% Cu(I) in the presence of a stabilizing ligand. 'Click' reactions using the monopropargylamides were also effected in the absence of added cuprous salts by the application of liquid assisted grinding (LAG) in metallic copper reaction vials. Specifically, high speed vibration ball milling (HSVBM) using a 3/32″ (2.38 mm) diameter copper ball (62 mg) at 60 Hz overnight in the presence of ethyl acetate lead to complete consumption of the 5'-azido nucleoside with clean conversion to the corresponding 1,3-triazole. PMID:25874944

  5. Reaction of alkynes and azides: not triazoles through copper-acetylides but oxazoles through copper-nitrene intermediates.

    PubMed

    Haldón, Estela; Besora, Maria; Cano, Israel; Cambeiro, Xacobe C; Pericàs, Miquel A; Maseras, Feliu; Nicasio, M Carmen; Pérez, Pedro J

    2014-03-17

    Well-defined copper(I) complexes of composition [Tpm*(,Br) Cu(NCMe)]BF4 (Tpm*(,Br) =tris(3,5-dimethyl-4-bromo-pyrazolyl)methane) or [Tpa(*) Cu]PF6 (Tpa(*) =tris(3,5-dimethyl-pyrazolylmethyl)amine) catalyze the formation of 2,5-disubstituted oxazoles from carbonyl azides and terminal alkynes in a direct manner. This process represents a novel procedure for the synthesis of this valuable heterocycle from readily available starting materials, leading exclusively to the 2,5-isomer, attesting to a completely regioselective transformation. Experimental evidence and computational studies have allowed the proposal of a reaction mechanism based on the initial formation of a copper-acyl nitrene species, in contrast to the well-known mechanism for the copper-catalyzed alkyne and azide cycloaddition reactions (CuAAC) that is triggered by the formation of a copper-acetylide complex. PMID:24616053

  6. Hexaphenylbenzene-Stabilized Luminescent Silver Nanoclusters: A Potential Catalytic System for the Cycloaddition of Terminal Alkynes with Isocyanides.

    PubMed

    Pramanik, Subhamay; Bhalla, Vandana; Kumar, Manoj

    2015-10-21

    A hexaphenylbenzene (HPB)-based derivative bearing thiol groups has been designed and synthesized that undergoes aggregation-induced emission enhancement in mixed aqueous media to form rodlike fluorescent aggregates. These rodlike aggregates behave as a "not quenched" probe for the detection of silver ions and further act as reactors and stabilizers for reducing-agent-free preparation of blue luminescent silver nanoclusters at room temperature. The utilization of fluorescent supramolecular aggregates for the preparation of Ag NCs in mixed aqueous media is unprecedented in the literature. Moreover, the wet chemical method that we are reporting in the present paper for the preparation of luminescent silver nanoclusters is better than the other methods reported in the literature. Further, these in situ generated Ag NCs showed exceptional catalytic activity in the preparation of pyrroles involving cocyclization of isocyanides and terminal alkynes. Interestingly, the catalytic efficiency of in situ generated Ag NCs was found to be better than the other catalytic systems reported in the literature. PMID:26420310

  7. Azide-alkyne cycloaddition en route towards 1H-1,2,3-triazole-tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation.

    PubMed

    Kumar, Kewal; Carrère-Kremer, Séverine; Kremer, Laurent; Guérardel, Yann; Biot, Christophe; Kumar, Vipan

    2013-02-01

    A diverse range of triazoles were prepared following well established, Cu-mediated azide-alkyne cycloaddition reactions with the aim of probing the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The anti-tubercular evaluation studies of the synthesized conjugates revealed that none of the scaffolds exhibited any activity that restricted mycobacterial growth even at high doses. The introduction of various substituents onto the N-1 of the β-lactam ring, introducing mono- or di-ferrocenylchalcone substituents at the C-3 position as well as introducing a spacer of varying chain length failed to produce any significant enhancement in the activity profiles. The described protocol was a successful attempt on the inclusion of a ferrocene nucleus in the β-lactam family tethered via triazole linkers having metabolic stability and physicochemical favourability. PMID:23108229

  8. Green synthesis of copper nanoparticles using Ginkgo biloba L. leaf extract and their catalytic activity for the Huisgen [3+2] cycloaddition of azides and alkynes at room temperature.

    PubMed

    Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad

    2015-11-01

    During this study, we report the green synthesis of copper nanoparticles (Cu NPs) using Ginkgo biloba L. leaf extract as a reducing and stabilizing agent under surfactant-free conditions. The formation of Cu NPs is monitored by recording the UV-vis absorption spectra. The green synthesized Cu NPs are characterized by TEM, EDS, FT-IR and UV-visible techniques. According to UV-vis results, the synthesized Cu NPs by this method are quite stable even after one month indicating the stability of Cu NPs. In terms of environmental impact and economy, metallic Cu NPs offer several advantages over homogeneous and traditional heterogeneous catalysts. In addition, due to the increased metal surface area, Cu NPs shows very high catalytic activity for the Huisgen [3+2] cycloaddition of azides and alkynes at room temperature. Furthermore, the catalyst can be simply recovered and reused several times with almost no loss in activity. PMID:26164245

  9. Synthesis, antimicrobial activity, and membrane permeabilizing properties of C-terminally modified nisin conjugates accessed by CuAAC.

    PubMed

    Slootweg, Jack C; van der Wal, Steffen; Quarles van Ufford, H C; Breukink, Eefjan; Liskamp, Rob M J; Rijkers, Dirk T S

    2013-12-18

    Functionalization of the lantibiotic nisin with fluorescent reporter molecules is highly important for the understanding of its mode of action as a potent antimicrobial peptide. In addition to this, multimerization of nisin to obtain multivalent peptide constructs and conjugation of nisin to bioactive molecules or grafting it on surfaces can be attractive methods for interference with bacterial growth. Here, we report a convenient method for the synthesis of such nisin conjugates and show that these nisin derivatives retain both their antimicrobial activity and their membrane permeabilizing properties. The synthesis is based on the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) as a bioorthogonal ligation method for large and unprotected peptides in which nisin was C-terminally modified with propargylamine and subsequently efficiently conjugated to a series of functionalized azides. Two fluorescently labeled nisin conjugates together with a dimeric nisin construct were prepared while membrane insertion as well as antimicrobial activity were unaffected by these modifications. This study shows that C-terminal modification of nisin does not deteriorate biological activity in sharp contrast to N-terminal modification and therefore C-terminally modified nisin analogues are valuable tools to study the antibacterial mode of action of nisin. Furthermore, the ability to use stoichiometric amounts of the azide containing molecule opens up possibilities for surface tethering and more complex multivalent structures. PMID:24266643

  10. A mild preparation of alkynes from alkenyl triflates.

    PubMed

    Yang, Xiaowen; Wu, Dimin; Lu, Zhaohong; Sun, Hongbin; Li, Ang

    2016-06-28

    We report herein a protocol for preparing alkynes from alkenyl triflates. Stoichiometric LiCl promotes this transformation in DMF at ambient temperature. A range of terminal and internal alkynes were obtained smoothly. A one-pot procedure of alkyne formation/Cu-mediated Huisgen cycloaddition was developed, which may find use in synthesizing natural product-based probes. PMID:27030373

  11. Rapid access to novel 1,2,3-triazolo-heterocyclic scaffolds via tandem Knoevenagel condensation/azide-alkyne 1,3-dipolar cycloaddition reaction in one pot.

    PubMed

    Maurya, Ram Awatar; Adiyala, Praveen Reddy; Chandrasekhar, D; Reddy, Chada Narsimha; Kapure, Jeevak Sopanrao; Kamal, Ahmed

    2014-09-01

    An operationally simple, one-pot, two-step cascade method has been developed to afford biologically important fused 1,2,3-triazolo-heterocyclic scaffolds from 2-alkynyl aryl(heteroaryl) aldehydes and phenacyl azides. This unique atom economical transformation engages four reactive centers (aldehyde, alkyne, active methylene, and azide) under metal-free catalysis. PMID:24945583

  12. Construction of Azabicyclo[6.4.0]dodecatrienes Based on Rhodium(I)-Catalyzed Intramolecular [6+2] Cycloaddition between Azetidine, Allene, and Alkynes.

    PubMed

    Yasuda, Shigeo; Yokosawa, Haruna; Mukai, Chisato

    2016-01-01

    Treatment of the allenylazetidine-alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C-C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved. PMID:27373635

  13. Cycloadditions for Studying Nucleic Acids.

    PubMed

    Kath-Schorr, Stephanie

    2016-02-01

    Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the well-established copper(I)-catalyzed alkyne-azide cycloaddition reaction to copper free methods, such as the strain-promoted azide-alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels-Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers. PMID:27572987

  14. Assessment of the Full Compatibility of Copper(I)-Catalyzed Alkyne-Azide Cycloaddition and Oxime Click Reactions for bis-Labelling of Oligonucleotides

    PubMed Central

    Estalayo-Adriàn, Sandra; Lartia, Rémy; Meyer, Albert; Vasseur, Jean-Jacques; Morvan, François; Defrancq, Eric

    2015-01-01

    The conjugation of oligonucleotides with reporters is of great interest for improving their intrinsic properties or endowing new ones. In this context, we report herein a new procedure for the bis-labelling of oligonucleotides through oxime ligation (Click-O) and copper(I)-catalyzed alkyne–azide cycloaddition (Click-H). 5′-Azido and 3′-aldehyde precursors were incorporated into oligonucleotides, and subsequent coupling reactions through Click-O and Click-H (or vice versa) were successfully achieved. In particular, we exhaustively investigated the full compatibility of each required step for both tethering strategies. The results demonstrate that click Huisgen and click oxime reactions are fully compatible. However, whilst both approaches can deliver the targeted doubly conjugated oligonucleotide, the route involving click oxime ligation prior to click Huisgen is significantly more successful. Thus the reactions investigated here can be considered to be key elements of the chemical toolbox for the synthesis of highly sophisticated bioconjugates. PMID:25969815

  15. Azide vs Alkyne Functionalization in Pt(II) Complexes for Post-treatment Click Modification: Solid-State Structure, Fluorescent Labeling, and Cellular Fate.

    PubMed

    Wirth, Regina; White, Jonathan D; Moghaddam, Alan D; Ginzburg, Aurora L; Zakharov, Lev N; Haley, Michael M; DeRose, Victoria J

    2015-12-01

    Tracking of Pt(II) complexes is of crucial importance toward understanding Pt interactions with cellular biomolecules. Post-treatment fluorescent labeling of functionalized Pt(II)-based agents using the bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has recently been reported as a promising approach. Here we describe an azide-functionalized Pt(II) complex, cis-[Pt(2-azidobutyl)amido-1,3-propanediamine)Cl2] (1), containing the cis geometry and difunctional reactivity of cisplatin, and present a comparative study with its previously described alkyne-functionalized congener. Single-crystal X-ray diffraction reveals a dramatic change in the solid-state arrangement with exchange of the alkyne for an azide moiety wherein 1 is dominated by a pseudo-chain of Pt-Pt dimers and antiparallel alignment of the azide substituents, in comparison with a circular arrangement supported by CH/π(C≡C) interactions in the alkyne version. In vitro studies indicate similar DNA binding and click reactivity of both congeners observed by fluorescent labeling. Interestingly, complex 1 shows in vitro enhanced click reactivity in comparison to a previously reported azide-appended Pt(II) complex. Despite their similar behavior in vitro, preliminary in cellulo HeLa studies indicate a superior imaging potential of azide-functionalized 1. Post-treatment fluorescent labeling of 1 observed by confocal fluorescence microscopy shows nuclear and intense nucleolar localization. These results demonstrate the potential of 1 in different cell line localization studies and for future isolation and purification of Pt-bound targets. PMID:26512733

  16. Allyl-Assisted, Cu(I)-Catalyzed Azide-Alkyne Cycloaddition/Allylation Reaction: Assembly of the [1,2,3]Triazolo-4,5,6,7-tetrahydropyridine Core Structure.

    PubMed

    Deng, Xiaohu; Liang, Jimmy; Allison, Brett B; Dvorak, Curt; McAllister, Heather; Savall, Brad M; Mani, Neelakandha S

    2015-11-01

    We report a Cu(I)-catalyzed azide-alkyne-allyl halide three-component reaction for a one-pot synthesis of 1,4-disubstituted 5-allyl-1,2,3-triazoles. The allyl moiety provides not only the electrophile but also a coordinating ligand to Cu, which is essential for the reaction to occur under mild conditions. A concise synthesis of a potential drug candidate 1 is realized based on this key reaction. PMID:26458051

  17. Intermolecular Silacarbonyl Ylide Cycloadditions: A Direct Pathway to Oxasilacyclopentenes

    PubMed Central

    Bourque, Laura E.; Woerpel, K. A.

    2009-01-01

    Silacarbonyl ylides, generated by metal-catalyzed silylene transfer to carbonyls, participate in formal intermolecular 1,3-dipolar cycloaddition reactions with carbonyl compounds and alkynes to form dioxasilacyclopentane acetals and oxasilacyclopentenes in an efficient, one-step process. PMID:18922005

  18. Bioconjugation with strained alkenes and alkynes.

    PubMed

    Debets, Marjoke F; van Berkel, Sander S; Dommerholt, Jan; Dirks, A Ton J; Rutjes, Floris P J T; van Delft, Floris L

    2011-09-20

    The structural complexity of molecules isolated from biological sources has always served as an inspiration for organic chemists. Since the first synthesis of a natural product, urea, chemists have been challenged to prepare exact copies of natural structures in the laboratory. As a result, a broad repertoire of synthetic transformations has been developed over the years. It is now feasible to synthesize organic molecules of enormous complexity, and also molecules with less structural complexity but prodigious societal impact, such as nylon, TNT, polystyrene, statins, estradiol, XTC, and many more. Unfortunately, only a few chemical transformations are so mild and precise that they can be used to selectively modify biochemical structures, such as proteins or nucleic acids; these are the so-called bioconjugation strategies. Even more challenging is to apply a chemical reaction on or in living cells or whole organisms; these are the so-called bioorthogonal reactions. These fields of research are of particular importance because they not only pose a worthy challenge for chemists but also offer unprecedented possibilities for studying biological systems, especially in areas in which traditional biochemistry and molecular biology tools fall short. Recent years have seen tremendous growth in the chemical biology toolbox. In particular, a rapidly increasing number of bioorthogonal reactions has been developed based on chemistry involving strained alkenes or strained alkynes. Such strained unsaturated systems have the unique ability to undergo (3 + 2) and (4 + 2) cycloadditions with a diverse set of complementary reaction partners. Accordingly, chemistry centered around strain-promoted cycloadditions has been exploited to precisely modify biopolymers, ranging from nucleic acids to proteins to glycans. In this Account, we describe progress in bioconjugation centered around cycloadditions of these strained unsaturated systems. Being among the first to recognize the utility

  19. Cu (I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC): Synthesis of 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nor-testosterone-17β-yl acetates targeting progestational and antipro-liferative activities.

    PubMed

    Mohamed, Z H; El-Koussi, Nawal A; Mahfouz, Nadia M; Youssef, Adel F; Abdel Jaleel, Gehad A; Shouman, Samia A

    2015-06-01

    The progestational potency and selectivity of synthetic steroidal agonists can be enhanced by even larger chemical moieties at 17α-position of the steroid backbones. Hereby a series 5a-c and 6a-c of novel 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nortestosterone-17β-yl acetates were designed and synthesized using click chemistry approach searching progestogenic derivatives with potential anticancer activity. Compounds 5a,b and 6a,c have affected to different extents the three histopatho-logical parameters considered for evaluation of their progestational activity. The compounds 5a,b and 6a,c showed modifications in rat uterus at 35.7-34.8 nM levels with privileged endometrial thickening effect and least change of uterine weight relative to NEA at 52.9 nM level. Up to 40 mg/kg dose compounds 5b and 6c were non-toxic. Molecular docking of the ligands in PR showed in the majority of cases a conformational fitting into the active site different from that of the reference steroid NEA. Compound 6b revealed about 46.4% growth inhibition of CNS cancer SNB-75 cell line, 56% growth inhibition of renal cancer A498 cell line and 56.7% growth inhibition of prostate cancer PC-3 cell line which was mediated by cell cycle arrest. Drugability of the screened compounds showed tolerated results after being challenged to diverse physicochemical parameters. PMID:25942354

  20. Multi-component Cycloaddition Approaches in the Catalytic Asymmetric Synthesis of Alkaloid Targets†

    PubMed Central

    Perreault, Stéphane; Rovis, Tomislav

    2010-01-01

    Cycloaddition reactions are attractive strategies for rapid formation of molecular complexity in organic synthesis as multiple bonds are formed in a single process. To this end, several research groups have been actively involved in the development of catalytic methods to activate readily accessible π-components to achieve cycloadditions. However, the use of C-N π-components for the formation of heterocycles by these processes is less well developed. It has been previously demonstrated that the combination of different isocyanates with two alkynes yields pyridones of several types by metal-catalyzed [2+2+2] cycloadditions. The potential of this chemistry has been extended to alkenes as C-C π-components, allowing the formation of sp3-stereocenters. In this tutorial review directed towards [n+2+2] cycloaddition of heterocumulenes, alkynes and alkenes, the recent advances in catalytic asymmetric synthesis of indolizidine, quinolizidine and azocine skeletons are discussed. PMID:19847348

  1. Alkenes in [2+2+2] Cycloadditions.

    PubMed

    Domínguez, Gema; Pérez-Castells, Javier

    2016-05-10

    Participation of alkenes and allenes in [2+2+2] cycloaddition reactions has attracted much attention recently. This version of the well-established alkyne cyclotrimerization renders interesting products, such as cyclohexadienes and other polycycles, through cascade processes. Many mechanistic variations are observed when using certain metal complexes as catalysts. The frequent generation of stereogenic centers has prompted the development of efficient asymmetric versions. This Minireview summarizes the efforts reported to date on the use of double bonds as partners in [2+2+2] cyclotrimerizations. PMID:26918553

  2. Cu/Pd-Catalyzed, Three-Component Click Reaction of Azide, Alkyne, and Aryl Halide: One-Pot Strategy toward Trisubstituted Triazoles.

    PubMed

    Wei, Fang; Li, Haoyu; Song, Chuanling; Ma, Yudao; Zhou, Ling; Tung, Chen-Ho; Xu, Zhenghu

    2015-06-01

    A Cu/Pd-catalyzed, three-component click reaction of azide, alkyne, and aryl halide has been developed. By using this Cu/Pd transmetalation relay catalysis, a variety of 1,4,5-trisubstituted 1,2,3-triazoles were quickly assembled in one step in high yields with complete regioselectivity, just like assembling Lego bricks. Notably, different from the well-established CuAAC click reactions only working on terminal alkynes, this reaction offers an alternative solution for the problem of the click reaction of internal alkynes. PMID:26000564

  3. Resin-supported catalysts for CuAAC click reactions in aqueous or organic solvents.

    PubMed

    Presolski, Stanislav I; Mamidyala, Sreeman K; Manzenrieder, Florian; Finn, M G

    2012-10-01

    The copper-catalyzed azide-alkyne cycloaddition click reaction is a valuable process for the synthesis of libraries of drug candidates, derivatized polymers and materials, and a wide variety of other functional molecules. In some circumstances, the removal of the copper catalyst is both necessary and inconvenient. We describe here two immobilized forms of a Cu-binding ligand that has been shown to accelerate triazole formation under many different conditions, using different resin supports that are appropriate for aqueous or organic solvents. Copper leaching from these resins was modest, allowing them to be reused in many reaction/filtration cycles without recharging with metal ion. The utility of this catalyst form was demonstrated in the convenient synthesis of 20 N-acetylgalactosamine derivatives for biological testing. PMID:22946559

  4. Monofunctionalization of Dendrimers Using Microwave–Assisted 1,3 Dipolar Cycloadditions

    PubMed Central

    Yoon, Kunsang; Goyal, Poorva; Weck, Marcus

    2008-01-01

    Monofunctionalized polyamide-based dendrimers containing either a terminal azide or alkyne moiety have been designed and synthesized via a convergent synthetic approach. The monofunctionalization allows for the single attachment of a functional moiety in quantitative yields using 1,3 dipolar cycloadditions thereby opening the possibility for targeted dendrimer functionalization. PMID:17472392

  5. Copper-Catalyzed Azide–Alkyne Click Chemistry for Bioconjugation

    PubMed Central

    Presolski, Stanislav I.; Hong, Vu Phong; Finn, M.G.

    2012-01-01

    The copper-catalyzed azide-alkyne cycloaddition reaction is widely used for the connection of molecular entities of all sizes. A protocol is provided here for the process with biomolecules. Ascorbate is used as reducing agent to maintain the required cuprous oxidation state. Since these convenient conditions produce reactive oxygen species, five equivalents of a copper-binding ligand is used with respect to metal. The ligand both accelerates the reaction and serves as a sacrificial reductant, protecting the biomolecules from oxidation. A procedure is also described for testing the efficiency of the reaction under desired conditions for purposes of optimization, before expensive biological reagents are used. PMID:22844652

  6. Diversity Oriented Synthesis of Indoloazepinobenzimidazole and Benzimidazotriazolobenzodiazepine from N(1)-Alkyne-1,2-diamines.

    PubMed

    Kumar, Ravi; Arigela, Rajesh K; Samala, Srinivas; Kundu, Bijoy

    2015-12-14

    A one-pot protocol for the diversity oriented synthesis of two N-polyheterocycles indoloazepinobenzimidazole and benzimidazotriazolobenzodiazepine from a common N(1)-alkyne-1,2-diamine building block is described. The approach involves sequential formation of benzimidazole through cyclocondensation and oxidation, which is followed by the formation of either an azepine ring (through alkyne activation and 6-endo-dig cyclization, 1,2-migration with ring expansion, and re-aromatization), or diazepine and triazole rings through 1,3-dipolar cycloaddition. PMID:26525303

  7. Active low-valent niobium catalysts from NbCl5 and hydrosilanes for selective intermolecular cycloadditions.

    PubMed

    Satoh, Yasushi; Obora, Yasushi

    2011-10-21

    An active niobium catalyst was developed via a simple and nontoxic reduction method from NbCl(5)/hydrosilane and utilized for the selective [2 + 2 + 2] cycloaddition reaction of terminal alkynes and alkenes/α,ω-dienes, to give 1,3-cyclohexadiene derivatives in high yields with excellent chemo- and regioselectivity. PMID:21919436

  8. Cycloaddition Chemistry of Tetrafluorothiophene S,S-Dioxide.

    PubMed

    Lemal, David M

    2016-06-17

    Tetrafluorothiophene S,S-dioxide has been found to be a powerful and versatile cycloaddend that undergoes a wide range of reactions as a Diels-Alder diene, dienophile, and [2 + 2] addend. Because it dimerizes only slowly at high temperatures, a broad range of conditions are available for these transformations. Reactions with terminal alkynes yield products of both Diels-Alder and [2 + 2] cycloaddition. Remarkably, the orbital topology-forbidden [2 + 2] process sometimes dominates over the allowed Diels-Alder reaction. PMID:27246658

  9. Monitoring Wnt Protein Acylation Using an In Vitro Cyclo-Addition Reaction

    PubMed Central

    Tuladhar, Rubina; Yarravarapu, Nageswari; Lum, Lawrence

    2016-01-01

    We describe here a technique for visualizing the lipidation status of Wnt proteins using azide-alkyne cycloaddition chemistry (click chemistry) and SDS-PAGE. This protocol incorporates in vivo labeling of a Wnt-IgG Fc fusion protein using an alkynylated palmitate probe but departs from a traditional approach by incorporating a secondary cycloaddition reaction performed on single-step purified Wnt protein immobilized on protein A resin. This approach mitigates experimental noise by decreasing the contribution of labeling from other palmitoylated proteins and by providing a robust method for normalizing labeling efficiency based on protein abundance. PMID:27590147

  10. 1,3-Dipolar Cycloadditions of Diazo Compounds in the Presence of Azides.

    PubMed

    Aronoff, Matthew R; Gold, Brian; Raines, Ronald T

    2016-04-01

    The diazo group has untapped utility in chemical biology. The tolerance of stabilized diazo groups to cellular metabolism is comparable to that of azido groups. However, chemoselectivity has been elusive, as both groups undergo 1,3-dipolar cycloadditions with strained alkynes. Removing strain and tuning dipolarophile electronics yields diazo group selective 1,3-dipolar cycloadditions that can be performed in the presence of an azido group. For example, diazoacetamide but not its azido congener react with dehydroalanine residues, as in the natural product nisin. PMID:26981746

  11. Monitoring Wnt Protein Acylation Using an In Vitro Cyclo-Addition Reaction.

    PubMed

    Tuladhar, Rubina; Yarravarapu, Nageswari; Lum, Lawrence

    2016-01-01

    We describe here a technique for visualizing the lipidation status of Wnt proteins using azide-alkyne cycloaddition chemistry (click chemistry) and SDS-PAGE. This protocol incorporates in vivo labeling of a Wnt-IgG Fc fusion protein using an alkynylated palmitate probe but departs from a traditional approach by incorporating a secondary cycloaddition reaction performed on single-step purified Wnt protein immobilized on protein A resin. This approach mitigates experimental noise by decreasing the contribution of labeling from other palmitoylated proteins and by providing a robust method for normalizing labeling efficiency based on protein abundance. PMID:27590147

  12. A Chiral N,N'-Dioxide-Zn(II) Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers.

    PubMed

    Kang, Tengfei; Ge, Shulin; Lin, Lili; Lu, Yan; Liu, Xiaohua; Feng, Xiaoming

    2016-04-25

    A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N'-dioxide-zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives. PMID:27059528

  13. Siloxy alkynes in annulation reactions.

    PubMed

    Qian, Hui; Zhao, Wanxiang; Sun, Jianwei

    2014-12-01

    Siloxy alkynes are a family of versatile species in organic synthesis. This account reviews the annulation reactions of siloxy alkynes for the synthesis of a variety of carbo- and heterocyclic products. With various dipolarophiles or dipolarophile-like reaction partners, siloxy alkynes are capable of forming small (three- to six-membered) rings. Recently, we have expanded the scope to the synthesis of medium- and large-ring lactones, enabled by the design of new amphoteric molecules as well as a new ring-expansion strategy. These annulation reactions provide not only practically useful syntheses of cyclic molecules, but also important understanding of the fundamental reactivity of siloxy alkynes. PMID:25171137

  14. One-Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides.

    PubMed

    Rajasekar, Shanmugam; Yadagiri, Dongari; Anbarasan, Pazhamalai

    2015-11-16

    A general and efficient one-pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper-catalyzed alkyne and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective insertion of α-iminocarbenes onto the C3-H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one-pot. The reaction also showed excellent functional-group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one-pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro-β-carboline and tryptoline. PMID:26443500

  15. Cyclic polymers from alkynes.

    PubMed

    Roland, Christopher D; Li, Hong; Abboud, Khalil A; Wagener, Kenneth B; Veige, Adam S

    2016-08-01

    Cyclic polymers have dramatically different physical properties compared with those of their equivalent linear counterparts. However, the exploration of cyclic polymers is limited because of the inherent challenges associated with their synthesis. Conjugated linear polyacetylenes are important materials for electrical conductivity, paramagnetic susceptibility, optical nonlinearity, photoconductivity, gas permeability, liquid crystallinity and chain helicity. However, their cyclic analogues are unknown, and therefore the ability to examine how a cyclic topology influences their properties is currently not possible. We have solved this challenge and now report a tungsten catalyst supported by a tetraanionic pincer ligand that can rapidly polymerize alkynes to form conjugated macrocycles in high yield. The catalyst works by tethering the ends of the polymer to the metal centre to overcome the inherent entropic penalty of cyclization. Gel-permeation chromatography, dynamic and static light scattering, viscometry and chemical tests are all consistent with theoretical predictions and provide unambiguous confirmation of a cyclic topology. Access to a wide variety of new cyclic polymers is now possible by simply choosing the appropriate alkyne monomer. PMID:27442285

  16. Cyclic polymers from alkynes

    NASA Astrophysics Data System (ADS)

    Roland, Christopher D.; Li, Hong; Abboud, Khalil A.; Wagener, Kenneth B.; Veige, Adam S.

    2016-08-01

    Cyclic polymers have dramatically different physical properties compared with those of their equivalent linear counterparts. However, the exploration of cyclic polymers is limited because of the inherent challenges associated with their synthesis. Conjugated linear polyacetylenes are important materials for electrical conductivity, paramagnetic susceptibility, optical nonlinearity, photoconductivity, gas permeability, liquid crystallinity and chain helicity. However, their cyclic analogues are unknown, and therefore the ability to examine how a cyclic topology influences their properties is currently not possible. We have solved this challenge and now report a tungsten catalyst supported by a tetraanionic pincer ligand that can rapidly polymerize alkynes to form conjugated macrocycles in high yield. The catalyst works by tethering the ends of the polymer to the metal centre to overcome the inherent entropic penalty of cyclization. Gel-permeation chromatography, dynamic and static light scattering, viscometry and chemical tests are all consistent with theoretical predictions and provide unambiguous confirmation of a cyclic topology. Access to a wide variety of new cyclic polymers is now possible by simply choosing the appropriate alkyne monomer.

  17. Low-valent niobium-catalyzed intermolecular [2 + 2 + 2] cycloaddition of tert-butylacetylene and arylnitriles to form 2,3,6-trisubstituted pyridine derivatives.

    PubMed

    Satoh, Yasushi; Obora, Yasushi

    2013-08-01

    A catalytic system based on low-valent niobium has been developed, consisting of NbCl5, Zn, and an alkoxysilane. This combination has been shown to be an efficient catalyst for the synthesis of pyridine derivatives from the intermolecular cycloaddition of alkynes and nitriles via a niobacyclopentadiene intermediate. PMID:23848456

  18. Reactivity and Chemoselectivity of Allenes in Rh(I)-Catalyzed Intermolecular (5 + 2) Cycloadditions with Vinylcyclopropanes: Allene-Mediated Rhodacycle Formation Can Poison Rh(I)-Catalyzed Cycloadditions

    PubMed Central

    2015-01-01

    Allenes are important 2π building blocks in organic synthesis and engage as 2-carbon components in many metal-catalyzed reactions. Wender and co-workers discovered that methyl substituents on the terminal allene double bond counterintuitively change the reactivities of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with vinylcyclopropanes (VCPs). More sterically encumbered allenes afford higher cycloadduct yields, and such effects are also observed in other Rh(I)-catalyzed intermolecular cycloadditions. Through density functional theory calculations (B3LYP and M06) and experiment, we explored this enigmatic reactivity and selectivity of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with VCPs. The apparent low reactivity of terminally unsubstituted allenes is associated with a competing allene dimerization that irreversibly sequesters rhodium. With terminally substituted allenes, steric repulsion between the terminal substituents significantly increases the barrier of allene dimerization while the barrier of the (5 + 2) cycloaddition is not affected, and thus the cycloaddition prevails. Computation has also revealed the origin of chemoselectivity in (5 + 2) cycloadditions with allene-ynes. Although simple allene and acetylene have similar reaction barriers, intermolecular (5 + 2) cycloadditions of allene-ynes occur exclusively at the terminal allene double bond. The terminal double bond is more reactive due to the enhanced d−π* backdonation. At the same time, insertion of the internal double bond of an allene-yne has a higher barrier as it would break π conjugation. Substituted alkynes are more difficult to insert compared with acetylene, because of the steric repulsion from the additional substituents. This leads to the greater reactivity of the allene double bond relative to the alkynyl group in allene-ynes. PMID:25379606

  19. Enrichment of O-GlcNAc-modified peptides using novel thiol-alkyne and thiol-disulfide exchange.

    PubMed

    Tsumoto, Hiroki; Ogasawara, Daisuke; Hashii, Noritaka; Suzuki, Takayoshi; Akimoto, Yoshihiro; Endo, Tamao; Miura, Yuri

    2015-07-01

    We have developed a selective method for the enrichment of O-linked β-N-acetylglucosamine (O-GlcNAc)-modified peptides, which uses a newly synthesized thiol-alkyne and a thiol-disulfide exchange. First, O-GlcNAc-modified peptides were enzymatically labeled with an azide-containing GalNAc analog. Then, the azide moiety was reacted with thiol-alkyne through a copper(I)-catalyzed azide-alkyne cycloaddition. The thiol-modified peptides were enriched with thiol-reactive resin through a thiol-disulfide exchange. At least 500fmol of O-GlcNAc-modified peptides was selectively isolated from α-crystallin tryptic peptides and detected by mass spectrometry. This novel enrichment strategy could be used for O-GlcNAcome analysis of biological samples. PMID:25980911

  20. Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides.

    PubMed

    Dommerholt, Jan; Rutjes, Floris P J T; van Delft, Floris L

    2016-04-01

    A nearly forgotten reaction discovered more than 60 years ago-the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole-enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bioconjugation tool, the usefulness of cyclooctyne-azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide-alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent. PMID:27573141

  1. Evaluation of bicinchoninic acid as a ligand for copper(I)-catalyzed azide-alkyne bioconjugations.

    PubMed

    Christen, Erik H; Gübeli, Raphael J; Kaufmann, Beate; Merkel, Lars; Schoenmakers, Ronald; Budisa, Nediljko; Fussenegger, Martin; Weber, Wilfried; Wiltschi, Birgit

    2012-09-01

    The Cu(I)-catalyzed cycloaddition of terminal azides and alkynes (click chemistry) represents a highly specific reaction for the functionalization of biomolecules with chemical moieties such as dyes or polymer matrices. In this study we evaluate the use of bicinchoninic acid (BCA) as a ligand for Cu(I) under physiological reaction conditions. We demonstrate that the BCA-Cu(I)-complex represents an efficient catalyst for the conjugation of fluorophores or biotin to alkyne- or azide-functionalized proteins resulting in increased or at least equal reaction yields compared to commonly used catalysts like Cu(I) in complex with TBTA (tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine) or BPAA (bathophenanthroline disulfonic acid). The stabilization of Cu(I) with BCA represents a new strategy for achieving highly efficient bioconjugation reactions under physiological conditions in many application fields. PMID:22821135

  2. Preparation and reactions of sugar azides with alkynes: synthesis of sugar triazoles as antitubercular agents.

    PubMed

    Singh, Biswajit Kumar; Yadav, Amit Kumar; Kumar, Brijesh; Gaikwad, A; Sinha, Sudhir Kumar; Chaturvedi, Vinita; Tripathi, Rama Pati

    2008-05-19

    5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition with different alkynes in the presence of CuSO4 and sodium ascorbate gave the corresponding sugar triazoles in very good yields. The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubercular activity in vitro with MIC 12.5 microg/mL. PMID:18346719

  3. One-pot synthesis of 2,5-dihydropyrroles from terminal alkynes, azides, and propargylic alcohols by relay actions of copper, rhodium, and gold.

    PubMed

    Miura, Tomoya; Tanaka, Takamasa; Matsumoto, Kohei; Murakami, Masahiro

    2014-12-01

    Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give α-allenyl-α-amino ketones. Finally, a gold catalyst prompts 5-endo cyclization to produce 2,5-dihydropyrroles. PMID:25345587

  4. Lewis Acid Catalysis in the Oxidative Cycloaddition of Thiophenes(1).

    PubMed

    Li, Yuanqiang; Thiemann, Thies; Sawada, Tsuyoshi; Mataka, Shuntaro; Tashiro, Masashi

    1997-11-14

    Thiophenes 1 were treated with m-chloroperbenzoic acid (m-CPBA) under BF(3).Et(2)O catalysis to afford thiophene S-monoxides. These could be reacted in situ as intermediary species with a number of dienophiles to provide arenes (with alkynes as dienophiles) or 7-thiabicyclo[2.2.1]hept-2-ene 7-oxides (with alkenes as dienophiles). It was also possible to isolate thiophene S-monoxides in solution and to cycloadd them in a second step. In either way it could be shown that the use of BF(3).Et(2)O enhances the yields of the oxidative cycloaddition of thiophenes considerably. Moreover a greater variety of dienophiles (29a, 29b, 29c) could be reacted with thiophenes than in the case of the noncatalyzed reaction. All cycloadditions catalyzed by BF(3).Et(2)O give only a single diastereoisomer as cycloadduct. The reactions show a high pi-facial selectivity, a fact that can be explained by the Cieplak-effect. Without added dienophiles, 2-methylthiophene (1e) gave a single dimer (36) of 2-methylthiophene S-monoxide, whereas 2,5-dimethylthiophene (1a) gave three dimers (32a-c). In the case of tetrasubstituted thiophenes, thiophene S-monoxides (e.g., 31b and 31c) could be isolated in substance. PMID:11671894

  5. Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides.

    PubMed

    Tan, Darlene Q; Atherton, Amy L; Smith, Austin J; Soldi, Cristian; Hurley, Katherine A; Fettinger, James C; Shaw, Jared T

    2012-03-12

    Formal cycloaddition reactions between imines and cyclic anhydrides serve as starting point for the synthesis of diverse libraries of small molecules. The synthesis of succinic anhydrides substituted with electron-withdrawing groups is facilitated by new mild conditions for alkylation of aryl-substituted acetyl esters with ethyl bromoacetate. These anhydrides are then used in formal cycloaddition reactions with imines to produce γ-lactams. 2-Fluoro-5-nitrophenylsuccinic anhydride reacts efficiently with imines to provide lactams that are further diversified by conversion of the nitro group to either an aniline and an azide for subsequent reactions with acylating agents and alkynes, respectively. The synthesis of cyanosuccinic anhydride is reported for the first time, and the use of this compound in reactions with imines and subsequent functionalization of the resultant lactams is demonstrated. PMID:22225535

  6. Discovery and Development of a Three-Component Oxidopyrylium [5 + 2] Cycloaddition.

    PubMed

    D'Erasmo, Michael P; Meck, Christine; Lewis, Chad A; Murelli, Ryan P

    2016-05-01

    α-Hydroxy-γ-pyrone-based oxidopyrylium cycloaddition reactions are useful methods for accessing a highly diverse range of oxabicyclo[3.2.1]octane products. Intermolecular variants of the reaction require the formation of a methyl triflate-based pre-ylide salt that upon treatment with base in the presence of alkenes or alkynes leads to α-methoxyenone-containing bicyclic products. Herein, we describe our discovery that the use of ethanol-stabilized chloroform as solvent leads to the generation of α-ethoxyenone-containing bicyclic byproducts. This three-component process was further optimized by gently heating a mixture of a purified version of the oxidopyrylium dimer in the presence of an alcohol prior to addition of a dipolarophile. Using this convenient procedure, several new oxidopyrylium cycloaddition products can be generated in moderate yields. We also highlight the method in a tandem ring-opening/debenzylation method for the generation of α-hydroxytropolones. PMID:27018974

  7. Synthesis of α-amino ketones from terminal alkynes via rhodium-catalyzed denitrogenative hydration of N-sulfonyl-1,2,3-triazoles.

    PubMed

    Miura, Tomoya; Biyajima, Tsuneaki; Fujii, Tetsuji; Murakami, Masahiro

    2012-01-11

    N-Sulfonyl-1,2,3-triazoles react with water in the presence of a rhodium catalyst to produce α-amino ketones in high yield. An intermediary α-imino rhodium(II) carbenoid undergoes insertion into the O-H bond of water. This transformation formally achieves 1,2-aminohydroxylation of terminal alkynes in a regioselective fashion when combined with the copper(I)-catalyzed 1,3-dipolar cycloaddition with N-sulfonyl azides. PMID:22129424

  8. [18F]azadibenzocyclooctyne ([18F]ADIBO): a biocompatible radioactive labeling synthon for peptides using catalyst free [3+2] cycloaddition.

    PubMed

    Arumugam, Selvanathan; Chin, Joshua; Schirrmacher, Ralf; Popik, Vladimir V; Kostikov, Alexey P

    2011-12-01

    N-Terminally azido-modified peptides were labeled with the novel prosthetic labeling synthon [(18)F]azadibenzocyclooctyne ([(18)F]ADIBO) using copper-free azide-alkyne [3+2]-dipolar cycloaddition in high radiochemical yields (RCYs). (18)F-Labeled [(18)F]ADIBO was prepared by nucleophilic substitution of the corresponding tosylate in 21% overall RCY (EOB) in a fully automated synthesis unit within 55 min. [(18)F]ADIBO was incubated with azide-containing peptides at room temperature in the absence of toxic metal catalysts and the formation of the triazole conjugate was confirmed. Finally, the azide-alkyne [3+2]-dipolar cycloaddition was shown to proceed with 95% radiochemical yield in ethanol within 30 min, allowing for a development of a kit-like peptide labeling approach with [(18)F]ADIBO. PMID:22024032

  9. Copper-catalyzed domino cycloaddition/C-N coupling/cyclization/(C-H arylation): an efficient three-component synthesis of nitrogen polyheterocycles.

    PubMed

    Qian, Wenyuan; Wang, Hao; Allen, Jennifer

    2013-10-11

    A cat of all trades: A single copper catalyst promoted up to three reaction steps with separate catalytic cycles in a domino sequence (azide-alkyne cycloaddition/Goldberg amidation/Camps cyclization/(CH arylation)) for the rapid construction of complex heterocycles from three simple components under mild conditions. Facile cleavage of the triazole ring enables further elaboration of the condensation products. PMID:24014265

  10. Three-component synthesis of C2F5-substituted pyrazoles from C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes

    PubMed Central

    2015-01-01

    Summary A one-pot reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes gives C2F5-substituted pyrazoles in excellent yields. The transformation smoothly proceeds in dichloromethane/water, tolerates the presence of air, and requires no purification of products by column chromatography. Mechanistically, C2F5CH2NH2·HCl and NaNO2 react first in water to generate C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane. PMID:25670987

  11. Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles.

    PubMed

    Kesornpun, Chatchai; Aree, Thammarat; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2016-03-14

    Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis. PMID:26914177

  12. Aryne cycloaddition with 3-oxidopyridinium species.

    PubMed

    Ren, Hailong; Wu, Chunrui; Ding, Xiuxiu; Chen, Xiaoge; Shi, Feng

    2012-12-01

    The [3 + 2] cycloaddition of arynes with 3-oxidopyridinium species is examined using the Kobayashi benzyne precursor. The reaction affords a bicyclo[3.2.1] skeleton under mild conditions. A [7 + 2] cycloaddition mode with a subsequent pyridine ring-opening event has also been observed. PMID:22976849

  13. Benzyne cycloaddition onto carbon nanohorns

    NASA Astrophysics Data System (ADS)

    Chronopoulos, Demetrios; Karousis, Nikolaos; Ichihashi, Toshinari; Yudasaka, Masako; Iijima, Sumio; Tagmatarchis, Nikos

    2013-06-01

    A facile approach for the covalent functionalization of carbon nanohorns (CNHs) based on the benzyne cycloaddition reaction is presented. The benzynes were in situ generated from either anthranilic acid by decomposition of the internal benzenediazonium-2-carboxylate or from 2-(trimethylsilyl)-phenyl triflate by fluoride ion attack at the silicon atom followed by displacement of the trimethylsilyl group under mild conditions. Moreover, the functionalization reaction was tested and performed under conventional conditions as well as under microwave irradiation. Modified CNHs possessing fused rings onto their graphitic skeleton were fully characterized by means of complementary spectroscopic techniques, thermogravimetric analysis, electron microscopy and light scattering. Moreover, Sonogashira coupling with propargyl alcohol followed by condensation with thioctic acid, to the iodo-modified CNHs obtained from the cycloaddition reaction of 2-amino-5-iodobenzoic acid with CNHs, resulted in the preparation of a new CNH-based material in which endocyclic disulfides are extended from the fused rings onto CNHs. The latter moieties were used to immobilize gold nanoparticles, furnishing the CNH-Aunano hybrid material, in which the former were identified with the aid of UV-Vis and EDX spectroscopy.A facile approach for the covalent functionalization of carbon nanohorns (CNHs) based on the benzyne cycloaddition reaction is presented. The benzynes were in situ generated from either anthranilic acid by decomposition of the internal benzenediazonium-2-carboxylate or from 2-(trimethylsilyl)-phenyl triflate by fluoride ion attack at the silicon atom followed by displacement of the trimethylsilyl group under mild conditions. Moreover, the functionalization reaction was tested and performed under conventional conditions as well as under microwave irradiation. Modified CNHs possessing fused rings onto their graphitic skeleton were fully characterized by means of complementary

  14. Enamine/butadienylborane cycloaddition in the frustrated Lewis pair regime.

    PubMed

    Chen, Guo-Qiang; Türkyilmaz, Fatma; Daniliuc, Constantin G; Bannwarth, Christoph; Grimme, Stefan; Kehr, Gerald; Erker, Gerhard

    2015-11-14

    The dienylborane 2a was prepared by regioselective alkyne hydroboration of the conjugated enyne 1a with Piers' borane [HB(C6F5)2]. Its reaction with a series of acetophenone derived enamines 3 resulted in the formation of the strong enamine β-carbon adduct with the borane Lewis acid (4). In contrast B-C adduct formation between the dienylborane 2a and a series of much more bulky cyclohexanone derived enamines (6) is rapidly reversible above ca.-30 °C and then leads to the formation of the [4 + 2]cycloaddition products 8. A DFT study revealed that this reaction is probably taking a stepwise route, proceeding by means of enamine addition to the dienylborane terminus to generate a zwitterionic borata-alkene/iminium ion intermediate that undergoes rapid subsequent ring closure. Heating of the products 8 led to amidoborane elimination from the vicinal amino/borane pair at the product framework to give the respective hexahydronaphthalene product 10. Subsequent treatment with TEMPO (2 equiv.) resulted in selective oxidation of the unsaturated ring to give the respective tetrahydronaphthalene derivative 12. PMID:26330093

  15. Preparation and Characterization of Macro- & Monomers for Azide & Alkyne Cycloaddition Polyerization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 1970 Robert Harper and colleagues, showed that poly(ethylene oxide)s and Poly(propylene oxide)s (PEOs and PPOs, respectively) are effective softeners for cotton fabrics (Textile Chemist and Colorist, 1970, 2(1), 37-41. Using this information, we developed PEO and PPO dibromides and diepoxides to ...

  16. Divergence in the reactivity between amine- and phosphine-catalyzed cycloaddition reactions of allenoates with enynals: one-pot gold-catalyzed synthesis of trisubstituted benzofurans from the [3 + 2] cycloadduct via 1,2-alkyl migration and dehydrogenation.

    PubMed

    Kumari, A Leela Siva; Swamy, K C Kumara

    2015-04-17

    Regioselective synthesis of functionalized dihydropyran derivatives by DABCO-catalyzed [2 + 4] cycloaddition of allenoates with enynals or enynones has been developed. Phosphine-catalyzed [3 + 2] cycloaddition of allenoates with enynals provides 1,1-alkyne (aldehyde)-substituted cyclopentenes wherein enynals act as electrophiles. These alkyne-tethered cyclopentenes upon [Au]/[Ag] catalysis lead to substituted benzofurans via 1,2-alkyl migration and dehydrogenation (aromatization). One-pot reaction of allenoates with enynals using sequential phosphine and gold catalysis is also reported. The cyclopentene obtained from the PPh3-catalyzed reaction of allenoate H2C═C═CH(COO-t-Bu) with enynal undergoes decarboxylation under the [Au]/[Ag] catalysis and forms a carboxylate-free benzofuran. The structures of key products are confirmed by single-crystal X-ray analysis. PMID:25793444

  17. Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

    PubMed Central

    Matassini, Camilla; Mirabella, Stefania; Goti, Andrea; Robina, Inmaculada; Moreno-Vargas, Antonio J

    2015-01-01

    Summary The synthesis of new multivalent architectures based on a trihydroxypiperidine α-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC) between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human glycosidases. PMID:26734108

  18. Intramolecular [2+2+2] cycloaddition of bis(propargylphenyl)carbodiimides: synthesis of L-shaped π-extended compounds with pyrrolo[1,2-a][1,8]naphthyridine corner units.

    PubMed

    Otani, Takashi; Saito, Takao; Sakamoto, Ryota; Osada, Hiroyuki; Hirahara, Akihito; Furukawa, Naoki; Kutsumura, Noriki; Matsuo, Tsukasa; Tamao, Kohei

    2013-07-14

    L-shaped π-extended penta-, hexa-, and heptacycles with a pyrrolo[1,2-a][1,8]naphthyridine junction were prepared from N,N'-bis[2-(2-alkyn-1-yl)phenyl]carbodiimides or their naphthyl analogs via Rh(I)-catalyzed intramolecular [2+2+2] cycloaddition and dehydrogenative aromatization. These L-shaped compounds emit sky-blue, yellow-green, or golden-orange fluorescence, with high quantum yields. PMID:23736526

  19. Synthesis and in vitro evaluation of potential anticancer activity of mono- and bis-1,2,3-triazole derivatives of bis-alkynes.

    PubMed

    Elamari, Hichem; Slimi, Riadh; Chabot, Guy G; Quentin, Lionel; Scherman, Daniel; Girard, Christian

    2013-02-01

    In order to find new molecules with cytotoxic activity against cancer cells, we prepared bis-akyne amides derived from propiolic acid. The bis-alkynes were then transformed in their mono-1,2,3-triazole analogs onto the amide side, due to its greater reactivity, using a catalyst-free Huisgen's reaction. The mono-triazoles were then subjected to the copper (I)-catalyzed version of the previous reaction (CuAAC), using a supported catalyst, to produce bis-triazoles. All products were obtained pure after simple trituration or filtration procedures. All synthetic compounds were tested in vitro for their cytotoxic activity using B16 melanoma cells. Four compounds (7, 23, 25 and 33) showed activities in the micromolar range (<21 μM) whereas three compounds (3, 22 and 38) presented activity at low micromolar concentrations (<10 μM), and two analogs (2 and 13) were active at nanomolar levels (<1 μM). PMID:23314049

  20. Nitrous oxide as a 1,3-dipole: a theoretical study of its cycloaddition mechanism.

    PubMed

    Nguyen, L T; Proft, F D; Chandra, A K; Uchimaru, T; Nguyen, M T; Geerlings, P

    2001-09-01

    The 1,3-dipolar cycloadditions of nitrous oxide and substituted alkynes have been studied at the B3LYP/6-31G(d,p) level. The reaction is controlled by LUMO (dipole)--HOMO (dipolarofile) and involves aromatic transition structures. The shape of the potential energy surface and the regioselectivity are not affected by the polarity of the solvents, except in the case of N2O + HC triple bond CSiH3. Different reactivity criteria including FMO coefficients product C, local softness differences Delta, magnetic susceptibility anisotropy chi(anis), and nucleus-independent chemical shifts NICS were used to predict the regioselectivity in all studied cases; the C, Delta criteria turn out to give the best results among them. The aromaticity of the transition structure is not a factor in determining the regiochemistry of the cycloaddtition reactions. PMID:11529736

  1. Synthesis of Functionalized 1,4-Azaborinines by the Cyclization of Di-tert-butyliminoborane and Alkynes.

    PubMed

    Schäfer, Marius; Beattie, Nicholas A; Geetharani, K; Schäfer, Julian; Ewing, William C; Krahfuß, Mirjam; Hörl, Christian; Dewhurst, Rian D; Macgregor, Stuart A; Lambert, Christoph; Braunschweig, Holger

    2016-07-01

    Di-tert-butyliminoborane is found to be a very useful synthon for the synthesis of a variety of functionalized 1,4-azaborinines by the Rh-mediated cyclization of iminoboranes with alkynes. The reactions proceed via [2 + 2] cycloaddition of iminoboranes and alkynes in the presence of [RhCl(PiPr3)2]2, which gives a rhodium η(4)-1,2-azaborete complex that yields 1,4-azaborinines upon reaction with acetylene. This reaction is compatible with substrates containing more than one alkynyl unit, cleanly affording compounds containing multiple 1,4-azaborinines. The substitution of terminal alkynes for acetylene also led to 1,4-azaborinines, enabling ring substitution at a predetermined location. We report the first general synthesis of this new methodology, which provides highly regioselective access to valuable 1,4-azaborinines in moderate yields. A mechanistic rationale for this reaction is supported by DFT calculations, which show the observed regioselectivity to arise from steric effects in the B-C bond coupling en route to the rhodium η(4)-1,2-azaborete complex and the selective oxidative cleavage of the B-N bond of the 1,2-azaborete ligand in its subsequent reaction with acetylene. PMID:27286231

  2. Steric and Dynamic Parameters Influencing In Situ Cycloadditions to Form Triazole Inhibitors with Crystalline Acetylcholinesterase.

    PubMed

    Bourne, Yves; Sharpless, K Barry; Taylor, Palmer; Marchot, Pascale

    2016-02-10

    Ligand binding sites on acetylcholinesterase (AChE) comprise an active center, at the base of a deep and narrow gorge lined by aromatic residues, and a peripheral site at the gorge entry. These features launched AChE as a reaction vessel for in situ click-chemistry synthesis of high-affinity TZ2PA6 and TZ2PA5 inhibitors, forming a syn-triazole upon cycloaddition within the gorge from alkyne and azide reactants bound at the two sites, respectively. Subsequent crystallographic analyses of AChE complexes with the TZ2PA6 regioisomers demonstrated that syn product association is accompanied by side chain reorganization within the gorge, freezing-in-frame a conformation distinct from an unbound state or anti complex. To correlate inhibitor dimensions with reactivity and explore whether in situ cycloaddition could be accelerated in a concentrated, crystalline template, we developed crystal-soaking procedures and solved structures of AChE complexes with the TZ2PA5 regioisomers and their TZ2/PA5 precursors (2.1-2.7 Å resolution). The structures reveal motions of residue His447 in the active site and, unprecedentedly, residue Tyr341 at the gorge mouth, associated with TZ2 binding and coordinated with other side chain motions in the gorge that may guide AChE toward a transient state favoring syn-triazole formation. Despite precursor binding to crystalline AChE, coupling of rapid electric field fluctuations in the gorge with proper alignments of the azide and alkyne reactants to form the triazole remains a likely limiting step. These observations point to a prime requirement for AChE to interconvert dynamically between sequential conformations to promote favorable electrostatic factors enabling a productive apposition of the reactants for reactivity. PMID:26731630

  3. Cu-Free 1,3-Dipolar Cycloaddition Click Reactions To Form Isoxazole Linkers in Chelating Ligands for fac-[MI(CO)3]+ Centers (M = Re, 99mTc)

    PubMed Central

    2015-01-01

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to CuI-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[MI(CO)3]+ (M = Re, 99mTc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[MI(CO)3]+ complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. 99mTc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues. PMID:24483834

  4. Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold.

    PubMed

    Werkhoven, P R; Elwakiel, M; Meuleman, T J; Quarles van Ufford, H C; Kruijtzer, J A W; Liskamp, R M J

    2016-01-14

    Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120-CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes. PMID:26552661

  5. Synthesis of triazoles from nonactivated terminal alkynes via the three-component coupling reaction using a Pd(0)-Cu(I) bimetallic catalyst.

    PubMed

    Kamijo, Shin; Jin, Tienan; Huo, Zhibao; Yamamoto, Yoshinori

    2003-07-01

    The synthesis of triazoles via the three-component coupling reaction of unactivated terminal alkynes, allyl carbonate, and trimethylsiyl azide under the Pd(0)-Cu(I) bimetallic catalyst is developed. The reaction most probably proceeds through the formation of a pi-allylpalladium azide complex and a copper-acetylide followed by a successive [3 + 2] cycloaddition. The deallylation of the resulting allyltriazoles proceeds very easily by the Ru-catalyzed isomerization followed by the ozonolysis of the resulting propenyltriazoles to give the triazoles in high yields. PMID:12822981

  6. Biomedical Applications of Tetrazine Cycloadditions

    PubMed Central

    Devaraj, Neal K.; Weissleder, Ralph

    2011-01-01

    -step procedures that use more sterically hindered biotin–avidin interactions. Nanoparticles can be detected with fluorescence or magnetic resonance techniques. These strategies are now being routinely used on clinical samples for biomarker profiling to predict malignancy and patient outcome. Finally, we discuss recent results with tetrazine reactions used for in vivo molecular imaging applications. Rapid tetrazine cycloadditions allow modular labeling of small molecules with the most commonly used positron emission tomography isotope, 18F. Additionally, in recent work we have begun to apply this reaction directly in vivo for the pre-targeted imaging of solid tumors. Future work with tetrazine cycloadditions will undoubtedly lead to optimized protocols, improved probes, and additional biomedical applications. PMID:21627112

  7. Chiral hybrid inorganic-organic materials: synthesis, characterization, and application in stereoselective organocatalytic cycloadditions.

    PubMed

    Puglisi, Alessandra; Benaglia, Maurizio; Annunziata, Rita; Chiroli, Valerio; Porta, Riccardo; Gervasini, Antonella

    2013-11-15

    The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles, exploiting two different anchoring sites and two different linkers, is reported. Catalysts 1-4 were prepared starting from l-phenylalanine or l-tyrosine methyl esters and supporting the imidazolidinone onto silica by grafting protocols or azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully characterized by solid-state NMR, N2 physisorption, SEM, and TGA in order to provide structural assessments, including an evaluation of surface areas, pore dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder cycloadditions between cyclopentadiene and different aldehydes, affording results comparable to those obtained with the nonsupported catalyst (up to 91% yield and 92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The catalysts were recovered from the reaction mixture by simple filtration or centrifugation. The most active catalyst was recycled two times with some loss of catalytic efficiency and a small erosion of ee. PMID:24134403

  8. Ruthenium(0) Catalyzed Endiyne-α-Ketol [4+2] Cycloaddition: Convergent Assembly of Type II Polyketide Substructures via C-C Bond Forming Transfer Hydrogenation

    PubMed Central

    Saxena, Aakarsh; Perez, Felix; Krische, Michael J.

    2015-01-01

    Upon exposure of 3,4-benzannulated 1,5-diynes (benzo-endiynes) to α-ketols (α-hydroxyketones) in the presence of ruthenium(0) catalysts derived from Ru3(CO)12 and RuPhos or CyJohnPhos, successive redox-triggered C-C coupling occurs to generate products of [4+2] cycloaddition. The proposed catalytic mechanism involves consecutive alkyne-carbonyl oxidative couplings to form transient oxaruthana-cycles that suffer α-ketol mediated transfer hydrogenolysis. This process provides a new, convergent means of assembling Type II polyketide substructures. PMID:25938947

  9. A New Multicomponent Multicatalyst Reaction (MC)(2)R: Chemoselective Cycloaddition and Latent Catalyst Activation for the Synthesis of Fully Substituted 1,2,3-Triazoles.

    PubMed

    Yamamoto, Kosuke; Bruun, Theodora; Kim, Jung Yun; Zhang, Lei; Lautens, Mark

    2016-06-01

    A multicomponent multicatalyst reaction (MC)(2)R for constructing fully substituted 1,2,3-triazoles is reported. An application of chemoselectivity and latent catalysis in a sequence of multicatalytic reactions confers control over a number of undesired processes, where all of the reagents coexist in the same reaction vessel. The sequence of a chemoselective copper-catalyzed azide alkyne cycloaddition followed by a palladium/copper-catalyzed Sonogashira cross-coupling afforded 1,2,3-triazoles regioselectively with good to high yields and a broad scope. PMID:27213631

  10. Synthesis and characterization of new 1,4 and 1,5-disubstituted glucopyranosyl 1,2,3-triazole by 1,3-dipolar cycloaddition

    NASA Astrophysics Data System (ADS)

    El Moncef, Abdelkarim; El Hadrami, El Mestafa; Ben-Tama, Abdeslem; de Arellano, Carmen Ramírez; Zaballos-Garcia, Elena; Stiriba, Salah-Eddine

    2009-07-01

    A series of 1,4 and 1,5-disubstituted 1-(β- D-glucopyranosyl)-1,2,3-triazoles has been prepared in an efficient manner with excellent yields using the intermolecular 1,3-dipolar cycloaddition of 1-azido-2,3,4,6-tetra- O-acetyl-β- D-glucopyranose 2 to a variety of substituted alkynes phenylacethylene 3, propargyl alcohol 4, 2-butyn-1,4-diol, 5, 3-propargylbenzimidazole 6 and propargylpyrazole 7 in toluene. The reaction takes place with the formation of both 4- and 5-regioisomers.

  11. Optimizing the selectivity of DIFO-based reagents for intracellular bioorthogonal applications.

    PubMed

    Kim, Eun J; Kang, Dong W; Leucke, Hans F; Bond, Michelle R; Ghosh, Salil; Love, Dona C; Ahn, Jong-Seog; Kang, Dae-Ook; Hanover, John A

    2013-08-01

    One of the most commonly employed bioorthogonal reactions with azides is copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC, a 'click' reaction). More recently, the strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC, a copper-free 'click' reaction) was developed, in which an alkyne is sufficiently strained to promote rapid cycloaddition with an azide to form a stable triazole conjugate. In this report, we show that an internal alkyne in a strained ring system with two electron-withdrawing fluorine atoms adjacent to the carbon-carbon triple bond reacts to yield covalent adducts not only with azide moieties but also reacts with free sulfhydryl groups abundant in the cytosol. We have identified conditions that allow the enhanced reactivity to be tolerated when using such conformationally strained reagents to enhance reaction rates and selectivity for bioorthogonal applications such as O-GlcNAc detection. PMID:23770695

  12. Metalation of alkynes. 4. The methoxymercuration reaction

    SciTech Connect

    Bassetti, M.; Floris, B.; Spadafora, G. )

    1989-12-08

    Methoxymercuration of symmetrically and unsymmetrically substituted alkynes (4-octyne, 2-heptyne, 2-nonyne, 1,4-dimethoxy-2-butyne, 1,4-diacetoxy-2-butyne, methyl 2-octynoate, methyl phenylpropynoate, 1-phenylpropyne, 1-phenyl-1-pentyne, diphenylethyne) was investigated. The corresponding {alpha}-mercurated enol ethers were generally isolated and characterized, except for 4-octyne, 2-heptyne, and 2-nonyne, which yielded {alpha}-acetoxymercurio ketones. Methoxymercuration was investigated kinetically. The rate law is second order, first order in both alkyne and mercuric acetate. Arylalkynes are less reactive than alkyl derivatives and the reaction rate is decreased by electron-withdrawing substituents. Activation parameters were determined for selected substrates. The kinetic data are in agreement with an electrophilic associative rate-determining step. Product analysis results suggest the formation of a cationic intermediate, the nature of which may vary from an unsymmetrically bridged species to an open carbocation, depending on the substrate.

  13. Catalytic Aminohalogenation of Alkenes and Alkynes

    PubMed Central

    Chemler, Sherry R.; Bovino, Michael T.

    2013-01-01

    Catalytic aminohalogenation methods enable the regio- and stereoselective vicinal difunctionalization of alkynes, allenes and alkenes with amine and halogen moieties. A range of protocols and reaction mechanisms including organometallic, Lewis base, Lewis acid and Brønsted acid catalysis have been disclosed, enabling the regio- and stereoselective synthesis of halogen-functionalized acyclic amines and nitrogen heterocycles. Recent advances including aminofluorination and catalytic enantioselective aminohalogenation reactions are summarized in this review. PMID:23828735

  14. Nickel-Catalyzed Stereoselective Dicarbofunctionalization of Alkynes.

    PubMed

    Li, Zhaodong; García-Domínguez, Andrés; Nevado, Cristina

    2016-06-01

    A nickel-catalyzed three-component reaction involving terminal alkynes, boronic acids, and alkyl halides is presented herein. Trisubstituted alkenes can be obtained in a highly regio- and stereocontrolled manner by the simultaneous addition of both aryl and alkyl groups across the triple bond in a radical-mediated process. The reaction, devoid of air- and moisture-sensitive organometallic reagents and catalysts, is operationally simple and offers a broad scope and functional-group tolerance. PMID:27111115

  15. Kinetically Trapped Tetrahedral Cages via Alkyne Metathesis.

    PubMed

    Lee, Semin; Yang, Anna; Moneypenny, Timothy P; Moore, Jeffrey S

    2016-02-24

    In dynamic covalent synthesis, kinetic traps are perceived as disadvantageous, hindering the system from reaching its thermodynamic equilibrium. Here we present the near-quantitative preparation of tetrahedral cages from simple tritopic precursors using alkyne metathesis. While the cages are the presumed thermodynamic sink, we experimentally demonstrate that the products no longer exchange their vertices once they have formed. The example reported here illustrates that kinetically trapped products may facilitate high yields of complex products from dynamic covalent synthesis. PMID:26854552

  16. Tetramethyleneethane Equivalents: Recursive Reagents for Serialized Cycloadditions

    PubMed Central

    2015-01-01

    New reactions and reagents that allow for multiple bond-forming events per synthetic operation are required to achieve structural complexity and thus value with step-, time-, cost-, and waste-economy. Here we report a new class of reagents that function like tetramethyleneethane (TME), allowing for back-to-back [4 + 2] cycloadditions, thereby amplifying the complexity-increasing benefits of Diels–Alder and metal-catalyzed cycloadditions. The parent recursive reagent, 2,3-dimethylene-4-trimethylsilylbutan-1-ol (DMTB), is readily available from the metathesis of ethylene and THP-protected 4-trimethylsilylbutyn-1-ol. DMTB and related reagents engage diverse dienophiles in an initial Diels–Alder or metal-catalyzed [4 + 2] cycloaddition, triggering a subsequent vinylogous Peterson elimination that recursively generates a new diene for a second cycloaddition. Overall, this multicomponent catalytic cascade produces in one operation carbo- and heterobicyclic building blocks for the synthesis of a variety of natural products, therapeutic leads, imaging agents, and materials. Its application to the three step synthesis of a new solvatochromic fluorophore, N-ethyl(6-N,N-dimethylaminoanthracene-2,3-dicarboximide) (6-DMA), and the photophysical characterization of this fluorophore are described. PMID:25961416

  17. Alkyne Hydroacylation: Switching Regioselectivity by Tandem Ruthenium Catalysis

    PubMed Central

    Chen, Qing-An; Cruz, Faben A.; Dong, Vy M.

    2015-01-01

    By using tandem ruthenium-catalysis, internal alkynes can be coupled with aldehydes for the synthesis of β,γ-unsaturated ketones. The catalyst promotes alkyne transformations with high regioselectivity, with examples that include the differentiation of a methyl versus ethyl substituent on the alkyne. Mechanistic studies suggest that the regioselectivity results from a selective allene formation that is governed by allylic strain. PMID:25608143

  18. Reactions of strained hydrocarbons with alkene and alkyne metathesis catalysts.

    PubMed

    Carnes, Matthew; Buccella, Daniela; Siegrist, Theo; Steigerwald, Michael L; Nuckolls, Colin

    2008-10-29

    Here we describe the metathesis reactions of a strained eight-membered ring that contains both alkene and alkyne functionality. We find that the alkyne metathesis catalyst produces polymer through a ring-opening alkyne metathesis reaction that is driven by the strain release from the monomer. The strained monomer provides unusual reactivity with ruthenium-based alkene metathesis catalysts. We isolate a discrete trimeric species a Dewar benzene derivative that is locked in this form through an unsaturated cyclophane strap. PMID:18826219

  19. Mechanism and Selectivity of Ru(II) - and Rh(III) -Catalyzed Oxidative Spiroannulation of Naphthols and Phenols with Alkynes through a C-H Activation/Dearomatization Strategy.

    PubMed

    Zhang, Mei; Huang, Genping

    2016-06-27

    The ruthenium- and rhodium-catalyzed oxidative spiroannulation of naphthols and phenols with alkynes was investigated by means of density functional theory calculations. The results show that the reaction undergoes O-H deprotonation/C(sp(2) )-H bond cleavage through a concerted metalation-deprotonation mechanism/migratory insertion of the alkyne into the M-C bond to deliver the eight-membered metallacycle. However, the dearomatization through the originally proposed enol-keto tautomerization/C-C reductive elimination was calculated to be kinetically inaccessible. Alternatively, an unusual metallacyclopropene, generated from the isomerization of the eight-membered metallacycle through rotation of the C-C double bond, was identified as a key intermediate to account for the experimental results. The subsequent C-C coupling between the carbene carbon atom and the carbon atom of the 2-naphthol/phenol ring was calculated to be relatively facile, leading to the formation of the unexpected dearomatized products. The calculations reproduce quite well the experimentally observed formal [5+2] cycloaddition in the rhodium-catalyzed oxidative annulation of 2-vinylphenols with alkynes. The calculations show that compared with the case of 2-alkenylphenols, the presence of conjugation effects and less steric repulsion between the phenol ring and the vinyl moiety make the competing reductive oxyl migration become dominant, which enables the selectivity switch from the spiroannulation to the formal [5+2] cycloaddition. PMID:27225930

  20. Microwave-assisted syntheses of BODIPY-sugar conjugates through click chemistry and conjugate assembly into liposomes.

    PubMed

    Yalagala, Ravi Shekar; Mazinani, Sina Atrin; Maddalena, Lucas A; Stuart, Jeffrey A; Yan, Fengyang; Yan, Hongbin

    2016-04-01

    BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations. PMID:26918516

  1. Evidence of Splitting 1,2,3-Triazole into an Alkyne and Azide by Low Mechanical Force in the Presence of Other Covalent Bonds.

    PubMed

    Khanal, Ashok; Long, Fei; Cao, Bin; Shahbazian-Yassar, Reza; Fang, Shiyue

    2016-07-01

    The cycloaddition reaction of an alkyne and azide to form a 1,2,3-triazole is widely used in many areas. However, the stability of the triazole moiety under mechanical stress is unclear. To see if a triazole could be selectively split into an alkyne and azide in the presence of other typical covalent bonds, a mica surface functionalized with a molecule containing a triazole moiety in the middle and an activated ester at the end was prepared. An atomic force microscope (AFM) tip with amino groups on its surface was ramped over the mica surface at predefined locations, which could temporarily link the tip to the surface through amide bond formation. During retraction, the triazole or another bond in the linkage broke, and a force was recorded. The forces varied widely at different ramps from close to 0 pN to 860 pN due to nonspecific adhesions and to the inherent inconsistency of single bond rupture. If some of the forces were from triazole cycloreversion, there would be alkynes at the predefined ramping locations. The surface was reacted with an azide carboxylic acid followed by labeling with amino Au nanoparticles (AuNPs). AFM imaging revealed AuNPs at the predicted locations, which provided evidence that under certain conditions triazole could be split selectively in the presence of other bonds at forces below 860 pN. PMID:27246264

  2. Access to a welwitindolinone core using sequential cycloadditions.

    PubMed

    Trost, Barry M; McDougall, Patrick J

    2009-08-20

    A concise approach to the core skeleton of the welwitindolinone alkaloids was developed on the basis of sequential cycloaddition reactions. First, a palladium catalyzed enantioselective [6 + 3] trimethylenemethane cycloaddition onto a tropone nucleus was used to generate the requisite bicyclo[4.3.1]decadiene. Subsequent modifications to the cycloadduct allowed for an intramolecular [4 + 2] cycloaddition to generate the oxindole and complete the core of the natural product family. PMID:19606876

  3. Alkenylation of Arenes and Heteroarenes with Alkynes.

    PubMed

    Boyarskiy, Vadim P; Ryabukhin, Dmitry S; Bokach, Nadezhda A; Vasilyev, Aleksander V

    2016-05-25

    This review is focused on the analysis of current data on new methods of alkenylation of arenes and heteroarenes with alkynes by transition metal catalyzed reactions, Bronsted/Lewis acid promoted transformations, and others. The synthetic potential, scope, limitations, and mechanistic problems of the alkenylation reactions are discussed. The insertion of an alkenyl group into aromatic and heteroaromatic rings by inter- or intramolecular ways provides a synthetic route to derivatives of styrene, stilbene, chalcone, cinnamic acid, various fused carbo- and heterocycles, etc. PMID:27111159

  4. An alkyne metathesis-based route toortho-dehydrobenzannulenes

    SciTech Connect

    Miljanic, Ognjen S.; Vollhardt, Peter C.; Whitener, Glenn D.

    2002-11-07

    An application of alkyne metathesis to 1,2-di(prop-1-ynyl)arenes, producing dehydrobenzannulenes, is described. An efficient method for selective Sonogashira couplings of bromoiodoarenes under conditions of microwave irradiation is also reported.

  5. Copper-Catalyzed Perfluoroalkylthiolation of Alkynes with Perfluoroalkanesulfenamides.

    PubMed

    Tlili, Anis; Alazet, Sébastien; Glenadel, Quentin; Billard, Thierry

    2016-07-11

    Copper-catalyzed direct perfluoroalkylthiolation of alkynes by using the corresponding perfluoroalkanesulfenamide reagent is reported. The selective mono- and bis-perfluoroalkylthiolation of alkynes can be conducted under very mild conditions (no base, room temperature) in very good to excellent yields. This approach, which uses a low toxicity, inexpensive copper catalyst that incorporates a commercially available ligand, is applied in the absence of any additional base. Preliminary mechanistic investigations shed some light on the nature of the unprecedented reactivity observed. PMID:27334703

  6. Rhodium-Catalyzed Enantioselective Hydroamination of Alkynes with Indolines

    PubMed Central

    Chen, Qing-An; Chen, Zhiwei; Dong, Vy M.

    2016-01-01

    The hydroamination of internal alkynes via tandem rhodium-catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid-switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations. PMID:26107923

  7. De Novo Proteome Analysis of Genetically Modified Tumor Cells By a Metabolic Labeling/Azide-alkyne Cycloaddition Approach*

    PubMed Central

    Ballikaya, Seda; Lee, Jennifer; Warnken, Uwe; Schnölzer, Martina; Gebert, Johannes; Kopitz, Jürgen

    2014-01-01

    Activin receptor type II (ACVR2) is a member of the transforming growth factor type II receptor family and controls cell growth and differentiation, thereby acting as a tumor suppressor. ACVR2 inactivation is known to drive colorectal tumorigenesis. We used an ACVR2-deficient microsatellite unstable colon cancer cell line (HCT116) to set up a novel experimental design for comprehensive analysis of proteomic changes associated with such functional loss of a tumor suppressor. To this end we combined two existing technologies. First, the ACVR2 gene was reconstituted in an ACVR2-deficient colorectal cancer (CRC) cell line by means of recombinase-mediated cassette exchange, resulting in the generation of an inducible expression system that allowed the regulation of ACVR2 gene expression in a doxycycline-dependent manner. Functional expression in the induced cells was explicitly proven. Second, we used the methionine analog azidohomoalanine for metabolic labeling of newly synthesized proteins in our cell line model. Labeled proteins were tagged with biotin via a Click-iT chemistry approach enabling specific extraction of labeled proteins by streptavidin-coated beads. Tryptic on-bead digestion of captured proteins and subsequent ultra-high-performance LC coupled to LTQ Orbitrap XL mass spectrometry identified 513 proteins, with 25 of them differentially expressed between ACVR2-deficient and -proficient cells. Among these, several candidates that had already been linked to colorectal cancer or were known to play a key role in cell growth or apoptosis control were identified, proving the utility of the presented experimental approach. In principle, this strategy can be adapted to analyze any gene of interest and its effect on the cellular de novo proteome. PMID:25225355

  8. Bacterial Genome Mining of Enzymatic Tools for Alkyne Biosynthesis.

    PubMed

    Zhu, Xuejun; Su, Michael; Manickam, Kadhirvel; Zhang, Wenjun

    2015-12-18

    The alkyne is an important functionality widely used in material science, pharmaceutical science, and chemical biology, but the importance of this functionality is contrasted by the very limited number of enzymes known to be involved in alkyne biosynthesis. We recently reported the first known carrier protein-dependent pathway for terminal alkyne formation, and in silico analysis suggested that this mechanism could be widespread in bacteria. In this paper, we screened additional homologous gene cassettes presumed to be involved in alkyne biosynthesis using both in vitro biochemical study and an E. coli-polyketide synthase (PKS) reporting system for in vivo analysis. We discovered and characterized a new terminal alkyne biosynthetic pathway comprised of TtuA, -B, and -C from Teredinibacter turnerae T7901. While the acyl-CoA ligase homologue (TtuA) demonstrated promiscuity in the activation and loading of medium-chain fatty acids onto the carrier protein (TtuC), the desaturase homologue (TtuB) showed stringent substrate specificity toward C10 fatty acyl moieties. In addition, TtuB was demonstrated to be a bifunctional desaturase/acetylenase that efficiently catalyzed two sequential O2-dependent dehydrogenation reactions. A novel terminal-alkyne bearing polyketide was further produced upon coexpression of ttuABC and a PKS gene in E. coli. The discovery and characterization of TtuA, -B, and -C provides us with a new bifunctional desaturase/acetylenase for mechanistic and structural study and expands the scarce enzyme inventory for the biosynthesis of the alkyne functionality, which has important applications in synthetic and chemical biology. PMID:26441143

  9. Bacterial genome mining of enzymatic tools for alkyne biosynthesis

    PubMed Central

    Zhu, Xuejun; Su, Michael; Manickam, Kadhirvel; Zhang, Wenjun

    2015-01-01

    The alkyne is an important functionality widely used in material science, pharmaceutical science, and chemical biology, but the importance of this functionality is contrasted by the very limited number of enzymes known to be involved in alkyne biosynthesis. We recently reported the first known carrier protein-dependent pathway for terminal alkyne formation, and in silico analysis suggested that this mechanism could be widespread in bacteria. In this paper, we screened additional homologous gene cassettes presumed to be involved in alkyne biosynthesis using both in vitro biochemical study and an E. coli-polyketide synthase (PKS) reporting system for in vivo analysis. We discovered and characterized a new terminal alkyne biosynthetic pathway comprised of TtuA, B, and C from Teredinibacter turnerae T7901. While the acyl-CoA ligase homolog (TtuA) demonstrated promiscuity in the activation and loading of medium-chain fatty acids onto the carrier protein (TtuC), the desaturase homolog (TtuB) showed stringent substrate specificity towards C10 fatty acyl moieties. In addition, TtuB was demonstrated to be a bifunctional desaturase/acetylenase that efficiently catalyzed two sequential O2-dependent dehydrogenation reactions. A novel terminal-alkyne bearing polyketide was further produced upon co-expression of ttuABC and a PKS gene in E. coli. The discovery and characterization of TtuA, B, and C provides us with a new bifunctional desaturase/acetylenase for mechanistic and structural study and expands the scarce enzyme inventory for the biosynthesis of the alkyne functionality, which has important applications in synthetic and chemical biology. PMID:26441143

  10. Nitrone Cycloadditions of 1,2-Cyclohexadiene

    PubMed Central

    Barber, Joyann S.; Styduhar, Evan D.; Pham, Hung V.; McMahon, Travis C.; Houk, K. N.; Garg, Neil K.

    2016-01-01

    We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis. PMID:26854652

  11. Synchronous intramolecular cycloadditions of the polyene macrolactam polyketide heronamide C.

    PubMed

    Booth, Thomas J; Alt, Silke; Capon, Robert J; Wilkinson, Barrie

    2016-05-11

    A growing number of natural products appear to arise from biosynthetic pathways that involve pericyclic reactions. We show here that for the heronamides this can occur via two spontaneous pathways involving alternative thermal or photochemical intramolecular cycloadditions. PMID:27091090

  12. Formation of cyclopentadienyl and ruthenacyclopentadienyl derivatives through ynenyl-diyne and ynenyl-alkyne couplings onto a triruthenium cluster core.

    PubMed

    Cabeza, J A; del Río, I; García-Granda, S; Lavigne, G; Lugan, N; Moreno, M; Nombel, P; Pérez-Priede, M; Riera, V; Rodríguez, A; Suárez, M; van der Maelen, J F

    2001-06-01

    The compound [Ru3(mu-H)(mu3-eta2-ampy)(CO)9] (1; Hampy =2-amino-6-methylpyridine) reacts with diynes RC4R in THF at reflux temperature to give the ynenyl derivatives [Ru3(mu3-eta2-ampy)(mu-eta3-RC...CC-CHR)(mu-CO)2-(CO)6] (2: R=CH2OPh; 3: R=Ph). These products contain a 1,4-disubstituted butynen-3-yl ligand attached to two ruthenium atoms. The compound [Ru3(mu-eta2-ampy)[mu3-eta6-PhCC5(C...CPh)-HPh2](CO)7] (4), which contains an eta5-cyclopentadienyl ring and a bridging carbene fragment, has also been obtained from the reaction of 1 with diphenylbutadiyne. This compound arises from a remarkable [3+2] cycloaddition reaction of a preformed 1,4-diphenylbutynen-4-yl ligand with a triple bond of a second diphenylbutadiyne molecule. The reactivity of the ynenyl derivatives 2 and 3 with diynes and alkynes has been studied. In all cases, compounds of the general formula [Ru3(mu-eta2-ampy)[mu3-eta5-C(=CHR)C=CRCR1=CR2](CO)7] (5-17) have been obtained. They all contain a ruthenacyclopentadienyl fragment formed by coupling of the coordinated ynenyl ligand of 2 (R = CH2OPh) or 3 (R = Ph) with a triple bond of the new reagent (the CR1=CR2 fragment results from the incoming diyne or alkyne reagent). While most of the products derived from 2 have the alkenyl C=CHR fragment with a Z configuration (R cis to Ru), all the compounds obtained from 3 have this fragment with an E configuration. Except 2 and 3, all the cluster complexes described in this article have a five-electron donor ampy ligand attached to only two metal atoms, a coordination mode unprecedented in cluster chemistry. PMID:11446639

  13. Anti-Markovnikov hydroimination of terminal alkynes in gold-catalyzed pyridine construction from ammonia.

    PubMed

    Wang, Liliang; Kong, Lingbing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei

    2015-08-11

    Gold-catalyzed hydroimination of terminal alkynes, giving rise to anti-Markovnikov adducts concomitant with unstable Markovnikov adducts is described. The elementary step can be applied for the construction of pyridine derivatives from ammonia and alkynes. PMID:26144528

  14. Copper-free Sonogashira cross-coupling for functionalization of alkyne-encoded proteins in aqueous medium and in bacterial cells.

    PubMed

    Li, Nan; Lim, Reyna K V; Edwardraja, Selvakumar; Lin, Qing

    2011-10-01

    Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction ("click chemistry"), have provided chemical tools to study biomolecular dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biological applications has not been reported. In this work, we report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry. PMID:21899368

  15. Chiral Phosphoric Acid Catalyzed [3 + 2] Cycloaddition and Tandem Oxidative [3 + 2] Cycloaddition: Asymmetric Synthesis of Substituted 3-Aminodihydrobenzofurans.

    PubMed

    Gelis, Coralie; Bekkaye, Mathieu; Lebée, Clément; Blanchard, Florent; Masson, Géraldine

    2016-07-15

    Asymmetric [3 + 2] cycloaddition of quinones with ene- and thioene-carbamates was achieved by chiral phosphoric acid catalysis, providing the corresponding 3-amino-2,3-dihydrobenzofurans in excellent yields with moderate to good diastereoselectivities and excellent enantioselectivities. An asymmetric tandem oxidative cycloaddition protocol starting from hydroquinones was also accomplished with phenyliodine(III) diacetate and a chiral phosphoric acid in the same reaction vessel. PMID:27352020

  16. Synthesis of 1,2,3-triazol-1-yl-methaneboronic acids via click chemistry: an easy access to a new potential scaffold for protease inhibitors

    PubMed Central

    Romagnoli, Chiara; Caselli, Emilia; Prati, Fabio

    2015-01-01

    Stereoselective synthesis of previously unreported 1,2,3-triazol-1-yl-methaneboronic acids has been achieved from azidomethaneboronates by Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC). The proximity of the cycloaddition reaction center to the boronic group is not detrimental for the stability of the sp3-carbon-boron bond nor to the stereoisomeric composition, further expanding the field of application of click chemistry to new boronate substrates and offering a new potential scaffold for protease inhibitors. PMID:26257579

  17. Efficient Synthesis of Fluorescent Squaraine Rotaxane Dendrimers

    PubMed Central

    Xiao, Shuzhang; Fu, Na; Peckham, Kaitlin; Smith, Bradley D.

    2009-01-01

    A squaraine rotaxane scaffold with four alkynes groups is readily converted into a range of dendritic architectures using high yielding copper catalyzed alkyne azide cycloaddition (CuAAC) chemistry. A convergent synthesis approach is more efficient than a divergent pathway. Dendritic squaraine rotaxanes with peripheral amine groups can be further functionalized to produce multivalent deep-red fluorescent derivatives that exhibit high brightness and outstanding chemical stability in biological solution. The surface groups on these functionalized fluorescent dendrimers include guanidinium, mannose, and phosphatidylcholine. PMID:19957971

  18. Iron-catalyzed diboration and carboboration of alkynes.

    PubMed

    Nakagawa, Naohisa; Hatakeyama, Takuji; Nakamura, Masaharu

    2015-03-01

    An iron-catalyzed diboration reaction of alkynes with bis(pinacolato)diboron (B2pin2) and external borating agents (MeOB(OR)2) affords diverse symmetrical or unsymmetrical cis-1,2-diborylalkenes. The simple protocol for the diboration reaction can be extended to the iron-catalyzed carboboration of alkynes with primary and, unprecedentedly, secondary alkyl halides, affording various tetrasubstituted monoborylalkenes in a highly stereoselective manner. DFT calculations indicate that a boryliron intermediate adds across the triple bond of an alkyne to afford an alkenyliron intermediate, which can react with the external trapping agents, borates and alkyl halides. In situ trapping experiments support the intermediacy of the alkenyl iron species using radical probe stubstrates. PMID:25631242

  19. Rhodium(i)-catalysed intermolecular alkyne insertion into (2-pyridylmethylene)cyclobutenes.

    PubMed

    Matsuda, Takanori; Matsumoto, Takeshi

    2016-06-14

    Cyclobutenes with 2-pyridylmethylene groups at the 3 position underwent an intermolecular alkyne insertion reaction in the presence of a rhodium(i) catalyst at 170 °C to afford substituted benzenes. Among the different 2-pyridylmethylene groups examined, 3-methyl-2-pyridyl derivatives showed superior activity and readily coupled with various alkynes, including sterically demanding, heteroaromatic and terminal alkynes. PMID:27193826

  20. Difluorocarbene Addition to Alkenes and Alkynes in Continuous Flow.

    PubMed

    Rullière, Pauline; Cyr, Patrick; Charette, André B

    2016-05-01

    The first in-flow difluorocarbene generation and addition to alkenes and alkynes is reported. The application of continuous flow technology allowed for the controlled generation of difluorocarbene from TMSCF3 and a catalytic quantity of NaI. The in situ generated electrophilic carbene reacts smoothly with a broad range of alkenes and alkynes, allowing the synthesis of the corresponding difluorocyclopropanes and difluorocyclopropenes. The reaction is complete within a 10 min residence time at high reaction concentrations. With a production flow rate of 1 mmol/min, continuous flow chemistry enables scale up of this process in a green, atom-economic, and safe manner. PMID:27119573

  1. A Hydration of an Alkyne Illustrating Steam and Vacuum Distillation.

    ERIC Educational Resources Information Center

    Wasacz, J. P.; Badding, V. G.

    1982-01-01

    Reports on the conversion 2,5-dimethylhexyne-2,5-diol(I) to 2,2,5,5-tetramethyltetrahydrofuran-3-one(II) using aqueous mercuric sulfate without the use of acid. The experiment has been successfully performed in introductory organic chemistry laboratories demonstrating alkyne hydration, steam distillation, vacuum distillation, drying of organic…

  2. Method for transforming alkynes into (E)-dibromoalkenes.

    PubMed

    Xiang, Jiannan; Yuan, Rui; Wang, Ruijia; Yi, Niannian; Lu, Linghui; Zou, Huaxu; He, Weimin

    2014-12-01

    The highly stereoselective bromination of alkynes has been realized by using copper(II) bromide as both the reacting partner and the catalyst, offering a generally efficient synthesis of (E)-dibromoalkenes. The reaction conditions are exceptionally mild, and a wide range of functional groups are well tolerated. PMID:25407142

  3. Silver-catalysed intramolecular hydroamination of alkynes with trichloroacetimidates.

    PubMed

    Wong, Valerie H L; Hor, T S Andy; Hii, King Kuok Mimi

    2013-10-18

    Silver(I) complexes catalyse the intramolecular addition of trichloroacetimidates to alkynes. In the absence of a ligand, the selectivity of the reaction is dependent upon the nature of the counter-anion and solvent. The introduction of non-chelating nitrogeneous ligands suppresses competitive Brønsted acid catalysis, improving the yield and selectivity of the reaction. PMID:23999555

  4. Formation of Ruthenium Carbenes by gem‐Hydrogen Transfer to Internal Alkynes: Implications for Alkyne trans‐Hydrogenation

    PubMed Central

    Leutzsch, Markus; Wolf, Larry M.; Gupta, Puneet; Fuchs, Michael; Thiel, Walter; Farès, Christophe

    2015-01-01

    Abstract Insights into the mechanism of the unusual trans‐hydrogenation of internal alkynes catalyzed by {Cp*Ru} complexes were gained by para‐hydrogen (p‐H2) induced polarization (PHIP) transfer NMR spectroscopy. It was found that the productive trans‐reduction competes with a pathway in which both H atoms of H2 are delivered to a single alkyne C atom of the substrate while the second alkyne C atom is converted into a metal carbene. This “geminal hydrogenation” mode seems unprecedented; it was independently confirmed by the isolation and structural characterization of a ruthenium carbene complex stabilized by secondary inter‐ligand interactions. A detailed DFT study shows that the trans alkene and the carbene complex originate from a common metallacyclopropene intermediate. Furthermore, the computational analysis and the PHIP NMR data concur in that the metal carbene is the major gateway to olefin isomerization and over‐reduction, which frequently interfere with regular alkyne trans‐hydrogenation. PMID:27478268

  5. Formation of Ruthenium Carbenes by gem-Hydrogen Transfer to Internal Alkynes: Implications for Alkyne trans-Hydrogenation

    PubMed Central

    Leutzsch, Markus; Wolf, Larry M; Gupta, Puneet; Fuchs, Michael; Thiel, Walter; Farès, Christophe; Fürstner, Alois

    2015-01-01

    Insights into the mechanism of the unusual trans-hydrogenation of internal alkynes catalyzed by {Cp*Ru} complexes were gained by para-hydrogen (p-H2) induced polarization (PHIP) transfer NMR spectroscopy. It was found that the productive trans-reduction competes with a pathway in which both H atoms of H2 are delivered to a single alkyne C atom of the substrate while the second alkyne C atom is converted into a metal carbene. This “geminal hydrogenation” mode seems unprecedented; it was independently confirmed by the isolation and structural characterization of a ruthenium carbene complex stabilized by secondary inter-ligand interactions. A detailed DFT study shows that the trans alkene and the carbene complex originate from a common metallacyclopropene intermediate. Furthermore, the computational analysis and the PHIP NMR data concur in that the metal carbene is the major gateway to olefin isomerization and over-reduction, which frequently interfere with regular alkyne trans-hydrogenation. PMID:26332643

  6. A versatile pathway to end-functionalized cellulose ethers for click chemistry applications.

    PubMed

    Kamitakahara, Hiroshi; Suhara, Ryo; Yamagami, Mao; Kawano, Haruko; Okanishi, Ryoko; Asahi, Tomoyuki; Takano, Toshiyuki

    2016-10-20

    This paper describes a versatile pathway to heterobifunctional/telechelic cellulose ethers, such as tri-O-methyl cellulosyl azide and propargyl tri-O-methyl celluloside, having one free C-4 hydroxyl group attached to the glucosyl residue at the non-reducing end for the use in Huisgen 1,3-dipolar cycloaddition and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The one-step end-functionalization of cellulose ethers for molecular rod synthesis involves the introduction of two reactive groups at both ends of the cellulose molecule, and can afford linear triblock copolymers via CuAAC and further reactions. We were able to tailor the degree of polymerization of end-functionalized cellulose ethers with controlled amounts of a Lewis acid, namely SnCl4. Chemical structures of the above cellulose ethers and the reaction conditions for controlling molecular length are discussed. PMID:27474546

  7. Hierachical assembly of collagen mimetic peptides into biofunctional materials

    NASA Astrophysics Data System (ADS)

    Gleaton, Jeremy W.

    Collagen is a remarkably strong and prevalent protein distributed throughout nature and as such, collagen is an ideal material for a variety of medical applications. Research efforts for the development of synthetic collagen biomaterials is an area of rapid growth. Here we present two methods for the assembly of collagen mimetic peptides (CMPs). The initial approach prompts assembly of CMPs which contain modifications for metal ion-triggered assembly. Hierarchical assembly into triple helices, followed by formation of disks via hydrophobic interactions has been demonstrated. Metal-ion mediated assembly of these disks, using iron (II)-bipyrdine interactions, has been shown to form micron-sized cages. The nature of the final structures that form depends on the number of bipyridine moieties incorporated into the CMP. These hollow spheres encapsulate a range of molecular weight fluorescently labeled dextrans. Furthermore, they demonstrate a time dependent release of contents under a variety of thermal conditions. The second approach assembles CMPs via the copper-catalyzed alkyne-azide cycloaddition (CuAAC) and the strain-promoted alkyne-azide cycloaddition (SPAAC) reactions. CMPs that incorporate the unnatural amino acids L-propargylglycine and L-azidolysine form triple helices and demonstrate higher order assembly when reacted via CuAAC. Reaction of the alkyne/azide modified CMPs under CuAAC conditions was found to produce an crosslinked 3-dimensional network. Moreover, we demonstrate that polymers, such as, PEG, can be reacted with alkyne and azide CMP triple helices via CuAAC and SPAAC. This designed covalent CMP chemistry allows for high flexibility in integrating various chemical cues, such as cell growth and differentiation within the higher order structures.

  8. Alkyne-tag Raman imaging of bio-active small molecules in live cells

    NASA Astrophysics Data System (ADS)

    Ando, Jun; Palonpon, Almar F.; Yamakoshi, Hiroyuki; Dodo, Kosuke; Kawata, Satoshi; Sodeoka, Mikiko; Fujita, Katsumasa

    2015-12-01

    Raman microscopy is useful for molecular imaging and analysis of biological specimens. Here, we used alkyne containing a carbon-carbon triple bond as a Raman tag for observing small molecules in live cells. Alkyne tags can maintain original properties of target molecules with providing high chemical specificity owing to its distinct peak in a Raman-silent window of biomolecules. For demonstrations, alkyne-tagged thymidine and coenzyme Q analogue in live cells were visualized with high-spatial resolution. We extended the application of alkyne-tag imaging to visualize cell organelles and specific lipid components in artificial monolayer membranes.

  9. Metal-Free Markovnikov-Type Alkyne Hydration under Mild Conditions.

    PubMed

    Liu, Wenbo; Wang, Haining; Li, Chao-Jun

    2016-05-01

    A Markovnikov-type alkyne hydration protocol is presented using 20% CF3SO3H (TfOH) as the catalyst under unprecedented mild conditions applicable to various alkynes, including terminal arylalkynes, terminal nonfunctionalized aliphatic alkynes, and internal alkynes with excellent regioselectivity in good to excellent yields (average yields >85%). The reaction procedure operates under mild conditions (25-70 °C), with broad functional group compatibility, and uses only slightly more than a stoichiometric amount of water in the absence of any transition metal. The success of this protocol hinges upon the utilization of trifluoroethanol as the solvent. PMID:27082159

  10. Assessment of electrophile damage in a human brain endothelial cell line utilizing a clickable alkyne analog of 2-chlorohexadecanal.

    PubMed

    Nusshold, Christoph; Üllen, Andreas; Kogelnik, Nora; Bernhart, Eva; Reicher, Helga; Plastira, Ioanna; Glasnov, Toma; Zangger, Klaus; Rechberger, Gerald; Kollroser, Manfred; Fauler, Günter; Wolinski, Heimo; Weksler, Babette B; Romero, Ignacio A; Kohlwein, Sepp D; Couraud, Pierre-Olivier; Malle, Ernst; Sattler, Wolfgang

    2016-01-01

    Peripheral leukocytes aggravate brain damage by releasing cytotoxic mediators that compromise blood-brain barrier function. One of the oxidants released by activated leukocytes is hypochlorous acid (HOCl) that is formed via the myeloperoxidase-H2O2-chloride system. The reaction of HOCl with the endogenous plasmalogen pool of brain endothelial cells results in the generation of 2-chlorohexadecanal (2-ClHDA), a toxic, lipid-derived electrophile that induces blood-brain barrier dysfunction in vivo. Here, we synthesized an alkynyl-analog of 2-ClHDA, 2-chlorohexadec-15-yn-1-al (2-ClHDyA) to identify potential protein targets in the human brain endothelial cell line hCMEC/D3. Similar to 2-ClHDA, 2-ClHDyA administration reduced cell viability/metabolic activity, induced processing of pro-caspase-3 and PARP, and led to endothelial barrier dysfunction at low micromolar concentrations. Protein-2-ClHDyA adducts were fluorescently labeled with tetramethylrhodamine azide (N3-TAMRA) by 1,3-dipolar cycloaddition in situ, which unveiled a preferential accumulation of 2-ClHDyA adducts in mitochondria, the Golgi, endoplasmic reticulum, and endosomes. Thirty-three proteins that are subject to 2-ClHDyA-modification in hCMEC/D3 cells were identified by mass spectrometry. Identified proteins include cytoskeletal components that are central to tight junction patterning, metabolic enzymes, induction of the oxidative stress response, and electrophile damage to the caveolar/endosomal Rab machinery. A subset of the targets was validated by a combination of N3-TAMRA click chemistry and specific antibodies by fluorescence microscopy. This novel alkyne analog is a valuable chemical tool to identify cellular organelles and protein targets of 2-ClHDA-mediated damage in settings where myeloperoxidase-derived oxidants may play a disease-propagating role. PMID:26577177

  11. Cu-free click cycloaddition reactions in chemical biology†

    PubMed Central

    Jewett, John C.

    2010-01-01

    Bioorthogonal chemical reactions are paving the way for new innovations in biology. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems—in some cases, living organisms. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. PMID:20349533

  12. Copper-Catalyzed Trifluoromethylazidation of Alkynes: Efficient Access to CF3-Substituted Azirines and Aziridines.

    PubMed

    Wang, Fei; Zhu, Na; Chen, Pinhong; Ye, Jinxing; Liu, Guosheng

    2015-08-01

    A novel method for convenient access to CF3-containing azirines has been developed, and involves a copper-catalyzed trifluoromethylazidation of alkynes and a photocatalyzed rearrangement. Both terminal and internal alkynes are compatible with the mild reaction conditions, thus delivering the CF3-containing azirines in moderate to good yields. The azirines can be converted into various CF3-substituted aziridines. PMID:26088360

  13. Palladium-Catalyzed Intermolecular Aerobic Annulation of o-Alkenylanilines and Alkynes for Quinoline Synthesis.

    PubMed

    Zheng, Jia; Li, Zun; Huang, Liangbin; Wu, Wanqing; Li, Jianxiao; Jiang, Huanfeng

    2016-08-01

    A new approach to construct 2,3-disubstituted quinolines is described via Pd-catalyzed oxidative cyclization of o-vinylanilines and alkynes with molecular oxygen. This transformation is supposed to undergo intermolecular amination of alkyne, insertion of the olefin, and oxidative cleavage of C-C bond sequence. PMID:27418021

  14. Z-Selective Copper(I)-Catalyzed Alkyne Semihydrogenation with Tethered Cu-Alkoxide Complexes.

    PubMed

    Pape, Felix; Thiel, Niklas O; Teichert, Johannes F

    2015-11-01

    A highly stereoselective alkyne semihydrogenation with copper(I) complexes is reported. Copper-N-heterocyclic carbene complex catalysts, bearing an intramolecular Cu-O bond, allow for the direct transfer of both hydrogen atoms from dihydrogen to the alkyne. The corresponding alkenes can be isolated with high Z selectivity and negligible overreduction to the alkane. PMID:26395782

  15. Ruthenium-catalyzed cyclization of N-carbamoyl indolines with alkynes: an efficient route to pyrroloquinolinones.

    PubMed

    Manoharan, Ramasamy; Jeganmohan, Masilamani

    2015-09-21

    A regioselective synthesis of substituted pyrroloquinolinones via a ruthenium-catalyzed oxidative cyclization of substituted N-carbamoyl indolines with alkynes is described. The cyclization reaction was compatible with various symmetrical and unsymmetrical alkynes including substituted propiolates. Later, we performed the aromatization of pyrroloquinolinones into indole derivatives in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). PMID:26228840

  16. Palladium-Catalyzed Regioselective Difluoroalkylation and Carbonylation of Alkynes.

    PubMed

    Wang, Qiang; He, Yu-Tao; Zhao, Jia-Hui; Qiu, Yi-Feng; Zheng, Lan; Hu, Jing-Yuan; Yang, Yu-Chen; Liu, Xue-Yuan; Liang, Yong-Min

    2016-06-01

    A novel, four-component synthetic strategy to synthesize a series of β-difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C-C bonds (including one C-CF2 bond) and one C-O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction. PMID:27191858

  17. Highly Active Multidentate Ligand-Based Alkyne Metathesis Catalysts.

    PubMed

    Du, Ya; Yang, Haishen; Zhu, Chengpu; Ortiz, Michael; Okochi, Kenji D; Shoemaker, Richard; Jin, Yinghua; Zhang, Wei

    2016-06-01

    Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2-hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, and broad functional-group tolerance. The homodimerization and cyclooligomerization of monopropynyl or dipropynyl substrates, including challenging heterocycle substrates (e.g., pyridine), proceed efficiently at 40-55 °C in a closed system. The ligand structure and catalytic activity relationship has been investigated, which shows that the ortho groups of the multidentate phenol ligands are critical to the stability and activity of such a catalyst system. PMID:27113640

  18. Metal-Free on-Surface Photochemical Homocoupling of Terminal Alkynes.

    PubMed

    Colazzo, Luciano; Sedona, Francesco; Moretto, Alessandro; Casarin, Maurizio; Sambi, Mauro

    2016-08-17

    On-surface synthesis involving the homocoupling of aryl-alkynes affords the buildup of bisacetylene derivatives directly at surfaces, which in turn may be further used as ingredients for the production of novel functional materials. Generally, homocoupling of terminal alkynes takes place by thermal activation of molecular precursors on metal surfaces. However, the interaction of alkynes with surface metal atoms often induces unwanted reaction pathways when thermal energy is provided to the system. In this contribution we report about light-induced metal-free homocoupling of terminal alkynes on highly oriented pyrolitic graphite (HOPG). The reaction occurred with high efficiency and selectivity within a self-assembled monolayer (SAM) of aryl-alkynes and led to the generation of large domains of ordered butadiynyl derivatives. Such a photochemical uncatalyzed pathway represents an original approach in the field of topological C-C coupling at the solid/liquid interface. PMID:27437555

  19. Stereoselectivity of nitrile oxide cycloadditions to chiral allylic fluorides: experiment and theory.

    PubMed

    Prakesch, Michael; Grée, Danielle; Grée, René; Carter, Jennifer; Washington, Ilyas; Houk, K N

    2003-11-21

    The cycloadditions of nitrile oxides with new and previously studied allylic fluorides were examined. The 1,3-dipolar cycloaddition reactions were also investigated theoretically with density functional theory (B3LYP) based transition-state modelling. The predictions provided reasonable agreement with experiment, indicating that both steric and electronic effects have important influences on the stereoselectivities of these reactions. PMID:14639650

  20. The spontaneous formation of single-molecule junctions via terminal alkynes.

    PubMed

    Pla-Vilanova, Pepita; Aragonès, Albert C; Ciampi, Simone; Sanz, Fausto; Darwish, Nadim; Diez-Perez, Ismael

    2015-09-25

    Herein, we report the spontaneous formation of single-molecule junctions via terminal alkyne contact groups. Self-assembled monolayers that form spontaneously from diluted solutions of 1, 4-diethynylbenzene (DEB) were used to build single-molecule contacts and assessed using the scanning tunneling microscopy-break junction technique (STM-BJ). The STM-BJ technique in both its dynamic and static approaches was used to characterize the lifetime (stability) and the conductivity of a single-DEB wire. It is demonstrated that single-molecule junctions form spontaneously with terminal alkynes and require no electrochemical control or chemical deprotonation. The alkyne anchoring group was compared against typical contact groups exploited in single-molecule studies, i.e. amine (benzenediamine) and thiol (benzendithiol) contact groups. The alkyne contact showed a conductance magnitude comparable to that observed with amine and thiol groups. The lifetime of the junctions formed from alkynes were only slightly less than that of thiols and greater than that observed for amines. These findings are important as (a) they extend the repertoire of chemical contacts used in single-molecule measurements to 1-alkynes, which are synthetically accessible and stable and (b) alkynes have a remarkable affinity toward silicon surfaces, hence opening the door for the study of single-molecule transport on a semiconducting electronic platform. PMID:26314486

  1. Versatility of Alkyne-Modified Poly(Glycidyl Methacrylate) Layers for Click Reactions

    SciTech Connect

    Soto-Cantu, Dr. Erick; Lokitz, Bradley S; Hinestrosa Salazar, Juan Pablo; Deodhar, Chaitra; Messman, Jamie M; Ankner, John Francis; Kilbey, II, S Michael

    2011-01-01

    Functional soft interfaces are of interest for a variety of technologies. We describe three methods for preparing substrates with alkyne groups, which show versatility for 'click' chemistry reactions. Two of the methods have the same root: formation of thin, covalently attached, reactive interfacial layers of poly(glycidyl methacrylate) (PGMA) via spin coating onto silicon wafers followed by reactive modification with either propargylamine or 5-hexynoic acid. The amine or the carboxylic acid moieties react with the epoxy groups of PGMA, creating interfacial polymer layers decorated with alkyne groups. The third method consists of using copolymers comprising glycidyl methacrylate and propargyl methacrylate (pGP). The pGP copolymers are spin coated and covalently attached on silicon wafers. For each method, we investigate the factors that control film thickness and content of alkyne groups using ellipsometry, and study the nanophase structure of the films using neutron reflectometry. Azide-terminated polymers of methacrylic acid and 2-vinyl-4,4-dimethylazlactone synthesized via reversible addition-fragmentation chain transfer polymerization were attached to the alkyne-modified substrates using 'click' chemistry, and grafting densities in the range of 0.007-0.95 chains nm{sup -2} were attained. The maximum density of alkyne groups attained by functionalization of PGMA with propargylamine or 5-hexynoic acid was approximately 2 alkynes nm{sup -3}. The alkyne content obtained by the three decorating approaches was sufficiently high that it was not the limiting factor for the click reaction of azide-capped polymers.

  2. The spontaneous formation of single-molecule junctions via terminal alkynes

    NASA Astrophysics Data System (ADS)

    Pla-Vilanova, Pepita; Aragonès, Albert C.; Ciampi, Simone; Sanz, Fausto; Darwish, Nadim; Diez-Perez, Ismael

    2015-09-01

    Herein, we report the spontaneous formation of single-molecule junctions via terminal alkyne contact groups. Self-assembled monolayers that form spontaneously from diluted solutions of 1, 4-diethynylbenzene (DEB) were used to build single-molecule contacts and assessed using the scanning tunneling microscopy-break junction technique (STM-BJ). The STM-BJ technique in both its dynamic and static approaches was used to characterize the lifetime (stability) and the conductivity of a single-DEB wire. It is demonstrated that single-molecule junctions form spontaneously with terminal alkynes and require no electrochemical control or chemical deprotonation. The alkyne anchoring group was compared against typical contact groups exploited in single-molecule studies, i.e. amine (benzenediamine) and thiol (benzendithiol) contact groups. The alkyne contact showed a conductance magnitude comparable to that observed with amine and thiol groups. The lifetime of the junctions formed from alkynes were only slightly less than that of thiols and greater than that observed for amines. These findings are important as (a) they extend the repertoire of chemical contacts used in single-molecule measurements to 1-alkynes, which are synthetically accessible and stable and (b) alkynes have a remarkable affinity toward silicon surfaces, hence opening the door for the study of single-molecule transport on a semiconducting electronic platform.

  3. Synthesis of a Cytotoxic Amanitin for Biorthogonal Conjugation.

    PubMed

    Zhao, Liang; May, Jonathan P; Blanc, Antoine; Dietrich, David J; Loonchanta, Anastak; Matinkhoo, Kaveh; Pryyma, Alla; Perrin, David M

    2015-07-01

    Alpha-amanitin is an exceedingly toxic, naturally occurring, bicyclic octapeptide that inhibits RNA polymerase and results in cellular and organismal death. Here we report the straightforward synthesis of an amanitin analogue that exhibited near-native toxicity. A pendant alkyne was readily installed to enable copper-catalyzed alkyne-azide cycloaddition (CuAAC) to azido-rhodamine and two azide-bearing versions of the RGD peptide. The fluorescent toxin analogue entered cells and provoked morphological changes consistent with cell death. The latter two conjugates are as toxic as the parent alkyne precursor, which demonstrates that conjugation does not diminish toxicity. In addition, we showed that toxicity depends on a single diastereomer of the unnatural amino acid, dihydroxyisoleucine (DHIle), at position 3. The convenient synthesis of a heptapeptide precursor now provides access to bioactive amanitin analogues that may be readily conjugated to biomolecules of interest. PMID:26043184

  4. 1,3-Dipolar cycloaddition reactivities of perfluorinated aryl azides with enamines and strained dipolarophiles.

    PubMed

    Xie, Sheng; Lopez, Steven A; Ramström, Olof; Yan, Mingdi; Houk, K N

    2015-03-01

    The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA-enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine-azide cycloadditions. PMID:25553488

  5. 1,3-Dipolar Cycloaddition Reactivities of Perfluorinated Aryl Azides with Enamines and Strained Dipolarophiles

    PubMed Central

    Xie, Sheng; Lopez, Steven A.; Ramström, Olof; Yan, Mingdi; Houk, K. N.

    2015-01-01

    The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA–enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine–azide cycloadditions. PMID:25553488

  6. Isocyanide based [4+1] cycloaddition reactions: an indispensable tool in multi-component reactions (MCRs).

    PubMed

    Kaur, Tanpreet; Wadhwa, Preeti; Bagchi, Sourav; Sharma, Anuj

    2016-05-19

    The advent of cycloaddition reactions in the synthesis of heterocycles and their ever burgeoning applications in the fields of material chemistry, catalysis and drugs have been a profound scientific development. In particular, isocyanide based cycloaddition reactions have been harbingers of an exciting new chapter in the realms of organic synthesis. The emergence of numerous synthetic protocols utilizing formal cycloaddition of isocyanides with conjugated heterodienes has unleashed countless opportunities to design and synthesize diverse heterocyclic scaffolds. To date, there has not been any exclusive review on a formal [4+1] cycloaddition involving isocyanides. The present review highlights the journey of formal [4+1] cycloaddition reactions of isocyanides with diverse electrophilic substrates viz. oxadienes, azadienes, thioacyl imines, alkylidene amides, alkylidene hydrazines, α,β-unsaturated nitro compounds, α-thioxothioamides, nitroso alkenes, acyl imines, vinyl ketenes, vinyl isocyanates, etc. to afford functionalized pyrroles, imidazoles, furans, oxazoles, pyrazoles, etc. PMID:27063921

  7. Branching Out: Rhodium-Catalyzed Allylation with Alkynes and Allenes.

    PubMed

    Koschker, Philipp; Breit, Bernhard

    2016-08-16

    We present a new and efficient strategy for the atom-economic transformation of both alkynes and allenes to allylic functionalized structures via a Rh-catalyzed isomerization/addition reaction which has been developed in our working group. Our methodology thus grants access to an important structural class valued in modern organic chemistry for both its versatility for further functionalization and the potential for asymmetric synthesis with the construction of a new stereogenic center. This new methodology, inspired by mechanistic investigations by Werner in the late 1980s and based on preliminary work by Yamamoto and Trost, offers an attractive alternative to other established methods for allylic functionalization such as allylic substitution or allylic oxidation. The main advantage of our methodology consists of the inherent atom economy in comparison to allylic oxidation or substitution, which both produce stoichiometric amounts of waste and, in case of the substitution reaction, require prefunctionalization of the starting material. Starting out with the discovery of a highly branched-selective coupling reaction of carboxylic acids with terminal alkynes using a Rh(I)/DPEphos complex as the catalyst system, over the past 5 years we were able to continuously expand upon this chemistry, introducing various (pro)nucleophiles for the selective C-O, C-S, C-N, and C-C functionalization of both alkynes and the double-bond isomeric allenes by choosing the appropriate rhodium/bidentate phosphine catalyst. Thus, valuable compounds such as branched allylic ethers, sulfones, amines, or γ,δ-unsaturated ketones were successfully synthesized in high yields and with a broad substrate scope. Beyond the branched selectivity inherent to rhodium, many of the presented methodologies display additional degrees of selectivity in regard to regio-, diastereo-, and enantioselective transformations, with one example even proceeding via a dynamic kinetic resolution. Many advances

  8. Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles.

    PubMed

    Zhou, Shuguang; Wang, Jinhu; Wang, Lili; Chen, Kehao; Song, Chao; Zhu, Jin

    2016-08-01

    A Co(III)-catalyzed, internal and terminal alkyne-compatible indole synthesis protocol is reported herein. The N-amino (hydrazine) group imparts distinct, diverse reactivity patterns for directed C-H functionalization/cyclization reactions. Notable synthetic features include regioselectivity for a meta-substituted arylhydrazine, regioselectivity for a chain-branched terminal alkyne, formal incorporation of an acetylenic unit through C2-desilylation on a C2-silylated indole derivative, formal inversion of regioselectivity through consecutive C3-derivatization and C2-desilylation processes, and formal bond migration for a linear-chain terminal alkyne. PMID:27434348

  9. Highly Chemo-, Regio-, and Stereoselective Cobalt-Catalyzed Markovnikov Hydrosilylation of Alkynes.

    PubMed

    Guo, Jun; Lu, Zhan

    2016-08-26

    A highly chemo-, regio- and stereoselective cobalt-catalyzed Markovnikov hydrosilylation of alkynes was developed. Various functionalized groups, such as halides, free alcohols, free aniline, ketones, esters, amides, and nitriles are tolerated, which may lead to further applications and late-stage derivatizations. To date, this is the most efficient cobalt catalytic system (TOF=65 520 h(-1) ; TOF=turnover frequency) for hydrosilylation of alkynes. The Hiyama-Denmark cross-coupling reactions of vinylsilanes with aryl iodides underwent smoothly to afford 1,1-diarylethenes. A unique regioselectivity-controllable hydrosilylation/hydroboration reaction of alkynes was also described. PMID:27440515

  10. Anomalous ligand effect in gold(I)-catalyzed intramolecular hydroamination of alkynes.

    PubMed

    Gaggioli, Carlo Alberto; Ciancaleoni, Gianluca; Biasiolo, Luca; Bistoni, Giovanni; Zuccaccia, Daniele; Belpassi, Leonardo; Belanzoni, Paola; Tarantelli, Francesco

    2015-04-01

    We analyzed the ligand electronic effect in a gold(I)-catalyzed intramolecular alkyne hydroamination, through a DFT and charge-displacement function (CDF) study. We found that, in the presence of π-electron conjugation between the alkyne and the nucleophilic functionality, electron poor ligands modify the coordination mode and the geometric parameters of the substrate in such a way that, contrary to expectations, the activation barrier of the nucleophilic attack increases. This remarkable effect is due to the competition between alkyne activation and nucleophile deactivation. The general relevance of these findings is highlighted. PMID:25738820

  11. Zinc-Catalyzed Dehydrogenative Cross-Coupling of Terminal Alkynes with Aldehydes: Access to Ynones.

    PubMed

    Tang, Shan; Zeng, Li; Liu, Yichang; Lei, Aiwen

    2015-12-21

    Because of the lack of redox ability, zinc has seldom been used as a catalyst in dehydrogenative cross-coupling reactions. Herein, a novel zinc-catalyzed dehydrogenative C(sp(2) )H/C(sp)H cross-coupling of terminal alkynes with aldehydes was developed, and provides a simple way to access ynones from readily available materials under mild reaction conditions. Good reaction selectivity can be achieved with a 1:1 ratio of terminal alkyne and aldehyde. Various terminal alkynes and aldehydes are suitable in this transformation. PMID:26564779

  12. Fluoroform-Derived CuCF3 for Trifluoromethylation of Terminal and TMS-Protected Alkynes.

    PubMed

    He, Lisi; Tsui, Gavin Chit

    2016-06-17

    An efficient trifluoromethylation reaction of alkynes using a fluoroform-derived CuCF3 reagent is described. The CF3 source is the inexpensive industrial waste fluoroform (CF3H). The air-stable CuCF3 reagent can be prepared in large quantities and is convenient to use. Synthetically useful trifluoromethylated alkynes containing a wide range of functional groups were successfully synthesized under mild conditions. Both terminal and TMS-protected alkynes gave the products in one step. The beneficial effect of a diamine ligand tetramethylethylenediamine (TMEDA) with the fluoroform-derived CuCF3 reagent was also demonstrated. PMID:27258390

  13. Polystyrene or Magnetic Nanoparticles as Support in Enantioselective Organocatalysis? A Case Study in Friedel-Crafts Chemistry.

    PubMed

    Ranjbar, Sara; Riente, Paola; Rodríguez-Escrich, Carles; Yadav, Jagjit; Ramineni, Kishore; Pericàs, Miquel A

    2016-04-01

    Heterogenized versions of the second-generation MacMillan imidazolidin-4-one are described for the first time. This versatile organocatalyst has been supported on 1% DVB Merrifield resin and Fe3O4 magnetic nanoparticles through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The resulting catalytic materials have been successfully applied to the asymmetric Friedel-Crafts alkylation of indoles with α,β-unsaturated aldehydes. While both catalytic systems can be easily recovered and admit repeated recycling, the polystyrene-based catalyst shows higher stability and provides better stereoselectivities. PMID:27010999

  14. Alkenes as azido precursors for the one-pot synthesis of 1,2,3-triazoles catalyzed by copper nanoparticles on activated carbon.

    PubMed

    Alonso, Francisco; Moglie, Yanina; Radivoy, Gabriel; Yus, Miguel

    2013-05-17

    A one-pot protocol for the synthesis of 1,2,3-triazoles has been developed starting from inactivated alkenes and based on two click reactions: the azidosulfenylation of the carbon-carbon double bond and the copper-catalyzed azide-alkyne cycloaddition (CuAAC). High yields of the β-methylsulfanyl triazoles have been attained using CuNPs/C as catalyst, with other commercial copper catalysts being completely inactive. The versatility of the methylsulfanyl group has been demonstrated through a series of synthetic transformations, including direct access to 1-vinyl and 4-monosubstituted triazoles. PMID:23617398

  15. Catalytic Stereoselective Synthesis of Diverse Oxindoles and Spirooxindoles from Isatins

    PubMed Central

    MacDonald, Jacob P.; Badillo, Joseph J.; Arevalo, Gary E.; Silva-Garcia, Abel

    2015-01-01

    A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically-distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles. PMID:22449252

  16. A click strategy for the immobilization of MacMillan organocatalysts onto polymers and magnetic nanoparticles.

    PubMed

    Riente, Paola; Yadav, Jagjit; Pericàs, Miquel A

    2012-07-20

    A chemically modified, first generation MacMillan imidazolidin-4-one has been anchored onto 1% DVB Merrifield resin and Fe3O4 (5.3 ± 1.4 nm) magnetic nanoparticles through copper-catalyzed alkyne azide cycloaddition (CuAAC) reactions. The resulting immobilized catalysts have been successfully used in the asymmetric Friedel-Crafts alkylation of N-substituted pyrroles with α,β-unsaturated aldehydes. The PS-supported catalyst (B) showed higher catalytic activity and enantioselectivity, while the MNP-supported one (A) showed higher recyclability and could be used in a sequential process with intermediate magnetic decantation. PMID:22758605

  17. Synthesis and labeling of α-(2,9)-trisialic acid with cyanine dyes for imaging of glycan-binding receptors on living cells.

    PubMed

    Zhang, Xiao-tai; Gu, Zhen-yuan; Liu, Libing; Wang, Shu; Xing, Guo-wen

    2015-05-21

    A sugar epitope, α-(2,9)-trisialic acid, was synthesized and labeled by cyanine dyes through Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The cyanine tagged oligosialic acid can be utilized as an efficient fluorescent probe to image the glycan-binding receptors on PC-12 cells. The distribution of Sia-binding immunoglobulin-like lectins (Siglecs) for α-(2,9)-trisialic acid was visualized by Cy3/Cy5 or FRET channel fluorescence imaging. PMID:25896133

  18. 2'-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA.

    PubMed

    Haugland, Marius M; El-Sagheer, Afaf H; Porter, Rachel J; Peña, Javier; Brown, Tom; Anderson, Edward A; Lovett, Janet E

    2016-07-27

    Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2'-alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron-electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information. PMID:27409454

  19. Pseudo-Ligandless Click Chemistry for Oligonucleotide Conjugation.

    PubMed

    Mack, Stephanie; Fouz, Munira F; Dey, Sourav K; Das, Subha R

    2016-01-01

    Particularly for its use in bioconjugations, the copper-catalyzed (or copper-promoted) azide-alkyne cycloaddition (CuAAC) reaction or 'click chemistry', has become an essential component of the modern chemical biologist's toolbox. Click chemistry has been applied to DNA, and more recently, RNA conjugations, and the protocols presented here can be used for either. The reaction can be carried out in aqueous buffer, and uses acetonitrile as a minor co-solvent that serves as a ligand to stabilize the copper. The method also includes details on the analysis of the reaction product. © 2016 by John Wiley & Sons, Inc. PMID:27258688

  20. Forming Stereogenic Centers in Acyclic Systems from Alkynes.

    PubMed

    Vabre, Roxane; Island, Biana; Diehl, Claudia J; Schreiner, Peter R; Marek, Ilan

    2015-08-17

    The combined carbometalation/zinc homologation followed by reactions with α-heterosubstituted aldehydes and imines proceed through a chair-like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo-axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth-Evans transition structure for α-chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon-carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single-pot operation from simple alkynes. PMID:26130570

  1. π Activation of Alkynes in Homogeneous and Heterogeneous Gold Catalysis.

    PubMed

    Bistoni, Giovanni; Belanzoni, Paola; Belpassi, Leonardo; Tarantelli, Francesco

    2016-07-14

    The activation of alkynes toward nucleophilic attack upon coordination to gold-based catalysts (neutral and positively charged gold clusters and gold complexes commonly used in homogeneous catalysis) is investigated to elucidate the role of the σ donation and π back-donation components of the Au-C bond (where we consider ethyne as prototype substrate). Charge displacement (CD) analysis is used to obtain a well-defined measure of σ donation and π back-donation and to find out how the corresponding charge flows affect the electron density at the electrophilic carbon undergoing the nucleophilic attack. This information is used to rationalize the activity of a series of catalysts in the nucleophilic attack step of a model hydroamination reaction. For the first time, the components of the Dewar-Chatt-Duncanson model, donation and back-donation, are put in quantitative correlation with the kinetic parameters of a chemical reaction. PMID:27119994

  2. Copper-catalysed selective hydroamination reactions of alkynes

    NASA Astrophysics Data System (ADS)

    Shi, Shi-Liang; Buchwald, Stephen L.

    2015-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine and tolterodine.

  3. Copper-catalysed selective hydroamination reactions of alkynes.

    PubMed

    Shi, Shi-Liang; Buchwald, Stephen L

    2015-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine and tolterodine. PMID:25515888

  4. Copper-catalyzed selective hydroamination reactions of alkynes

    PubMed Central

    Shi, Shi-Liang; Buchwald, Stephen L.

    2014-01-01

    The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a longstanding goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective, and step-efficient synthesis of amines is still needed. In this work we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines, and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio-, and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine, and tolterodine. PMID:25515888

  5. Genetically Encoded Azide Containing Amino Acid in Mammalian Cells Enables Site-Specific Antibody-Drug Conjugates Using Click Cycloaddition Chemistry.

    PubMed

    VanBrunt, Michael P; Shanebeck, Kurt; Caldwell, Zachary; Johnson, Jeffrey; Thompson, Pamela; Martin, Thomas; Dong, Huifang; Li, Gary; Xu, Hengyu; D'Hooge, Francois; Masterson, Luke; Bariola, Pauline; Tiberghien, Arnaud; Ezeadi, Ebele; Williams, David G; Hartley, John A; Howard, Philip W; Grabstein, Kenneth H; Bowen, Michael A; Marelli, Marcello

    2015-11-18

    Antibody-drug conjugates (ADC) have emerged as potent antitumor drugs that provide increased efficacy, specificity, and tolerability over chemotherapy for the treatment of cancer. ADCs generated by targeting cysteines and lysines on the antibody have shown efficacy, but these products are heterogeneous, and instability may limit their dosing. Here, a novel technology is described that enables site-specific conjugation of toxins to antibodies using chemistry to produce homogeneous, potent, and highly stable conjugates. We have developed a cell-based mammalian expression system capable of site-specific integration of a non-natural amino acid containing an azide moiety. The azide group enables click cycloaddition chemistry that generates a stable heterocyclic triazole linkage. Antibodies to Her2/neu were expressed to contain N6-((2-azidoethoxy)carbonyl)-l-lysine at four different positions. Each site allowed over 95% conjugation efficacy with the toxins auristatin F or a pyrrolobenzodiazepine (PBD) dimer to generate ADCs with a drug to antibody ratio of >1.9. The ADCs were potent and specific in in vitro cytotoxicity assays. An anti Her2/neu conjugate demonstrated stability in vivo and a PBD containing ADC showed potent efficacy in a mouse tumor xenograph model. This technology was extended to generate fully functional ADCs with four toxins per antibody. The high stability of the azide-alkyne linkage, combined with the site-specific nature of the expression system, provides a means for the generation of ADCs with optimized pharmacokinetic, biological, and biophysical properties. PMID:26332743

  6. A surprising dipolar cycloaddition provides ready access to aminoglycosides.

    PubMed

    Dahl, Russell S; Finney, Nathaniel S

    2004-07-14

    This contribution describes the results of a new research effort in our laboratory aimed at the synthesis of novel aminoglycosides and amino-C-glycosides. Despite the importance of such compounds, and the previous development of some methodological solutions, this remains an important area of research. Notable features of our approach, which is distinct from and complementary to previous efforts, are the following: (1) Reliance on a surprising and unprecedented formation of glycal triazolines via an inverse electron demand dipolar cycloaddition of glucal. We believe this desirable transformation has not previously been discovered because of the unusual selection of substrates and solvent required. (2) Very mild reaction conditions. An initial thermal cycloaddition is carried out in an inert solvent, the triazoline generated is photochemically converted to a reactive aziridine, and the crude aziridine undergoes ring opening at room temperature in the presence of a nucleophile and a mild Lewis acid catalyst. (3) Formation of products lacking an N-acyl group, allowing ready synthesis of novel glucosamine derivatives. PMID:15237974

  7. Radical cascade reaction of alkynes with N-fluoroarylsulfonimides and alcohols.

    PubMed

    Zheng, Guangfan; Li, Yan; Han, Jingjie; Xiong, Tao; Zhang, Qian

    2015-01-01

    Cascade reactions initiated by radical addition to alkynes are synthetically very attractive because they enable access to highly complex molecular skeletons in only few synthetic steps under usually mild conditions. Here we report a general radical cascade reaction of alkynes, N-fluoroarylsulfonimides and alcohols, enabling the efficient synthesis of important α-amino-α-aryl ketones from readily available starting materials via a single operation. During this process, the highly regioselective nitrogen-centred radical addition to internal and terminal alkynes generating vinyl radicals and the next explicit migration of aryl group from the nitrogen source lead the following efficient desulfonylation, oxygenation, and semi-pinacol rearrangement. In addition, the semi-pinacol rearrangement precursors, α-alkyloxyl-α,α-diaryl imines, could also be efficiently obtained under milder conditions. This methodology might open a new entry for designing intermolecular radical cascade reaction of alkynes. PMID:25901840

  8. Cobalt-Catalyzed Annulation of Salicylaldehydes and Alkynes to Form Chromones and 4-Chromanones.

    PubMed

    Yang, Junfeng; Yoshikai, Naohiko

    2016-02-01

    A unique cobalt(I)-diphosphine catalytic system has been identified for the coupling of salicylaldehyde (SA) and an internal alkyne affording a dehydrogenative annulation product (chromone) or a reductive annulation product (4-chromanone) depending on the alkyne substituents. Distinct from related rhodium(I)- and rhodium(III)-catalyzed reactions of SA and alkynes, these annulation reactions feature aldehyde C-H oxidative addition of SA and subsequent hydrometalation of the C=O bond of another SA molecule as common key steps. The reductive annulation to 4-chromanones also involves the action of Zn as a stoichiometric reductant. In addition to these mechanistic features, the Co(I) catalysis described herein is complementary to the Rh(I) - and Rh(III) -catalyzed reactions of SA and internal alkynes, particularly in the context of chromone synthesis. PMID:26804050

  9. Copper-catalyzed azide-alkyne cycloaddition (click chemistry)-based Detection of Global Pathogen-host AMPylation on Self-assembled Human Protein Microarrays*

    PubMed Central

    Yu, Xiaobo; Woolery, Andrew R.; Luong, Phi; Hao, Yi Heng; Grammel, Markus; Westcott, Nathan; Park, Jin; Wang, Jie; Bian, Xiaofang; Demirkan, Gokhan; Hang, Howard C.; Orth, Kim; LaBaer, Joshua

    2014-01-01

    AMPylation (adenylylation) is a recently discovered mechanism employed by infectious bacteria to regulate host cell signaling. However, despite significant effort, only a few host targets have been identified, limiting our understanding of how these pathogens exploit this mechanism to control host cells. Accordingly, we developed a novel nonradioactive AMPylation screening platform using high-density cell-free protein microarrays displaying human proteins produced by human translational machinery. We screened 10,000 unique human proteins with Vibrio parahaemolyticus VopS and Histophilus somni IbpAFic2, and identified many new AMPylation substrates. Two of these, Rac2, and Rac3, were confirmed in vivo as bona fide substrates during infection with Vibrio parahaemolyticus. We also mapped the site of AMPylation of a non-GTPase substrate, LyGDI, to threonine 51, in a region regulated by Src kinase, and demonstrated that AMPylation prevented its phosphorylation by Src. Our results greatly expanded the repertoire of potential host substrates for bacterial AMPylators, determined their recognition motif, and revealed the first pathogen-host interaction AMPylation network. This approach can be extended to identify novel substrates of AMPylators with different domains or in different species and readily adapted for other post-translational modifications. PMID:25073739

  10. Rhodium-Catalyzed Cross-Cyclotrimerization and Dimerization of Allenes with Alkynes.

    PubMed

    Sakashita, Kazuki; Shibata, Yu; Tanaka, Ken

    2016-06-01

    It has been established that a cationic rhodium(I)/binap complex catalyzes the cross-cyclotrimerization of two molecules of a monosubstituted allene with one molecule of a functionalized alkyne to give 3,6-dialkylidenecyclohex-1-enes. In contrast, the reactions involving di- or trisubstituted allenes and/or unfunctionalized alkynes afforded cross-dimerization products, substituted dendralenes, through β-hydrogen elimination from the corresponding rhodacycles. PMID:27110668

  11. Fundamental Flame Velocities of Pure Hydrocarbons I : Alkanes, Alkenes, Alkynes Benzene, and Cyclohexane

    NASA Technical Reports Server (NTRS)

    Gerstein, Melvin; Levine, Oscar; Wong, Edgar L

    1950-01-01

    The flame velocities of 37 pure hydrocarbons including normal and branched alkanes, alkenes, and alkynes; as well as benzene and cyclohexane, together with the experimental technique employed are presented. The normal alkanes have about the same flame velocity from ethane through heptane with methane being about 16 percent lower. Unsaturation increases the flame velocity in the order of alkanes, alkenes, and alkynes. Branching reduces the flame velocity.

  12. Nickel-catalyzed reductive arylation of activated alkynes with aryl iodides

    PubMed Central

    Dorn, Stephanie C. M.; Olsen, Andrew K; Kelemen, Rachel E.; Shrestha, Ruja; Weix, Daniel J.

    2015-01-01

    The direct, regioselective, and stereoselective arylation of activated alkynes with aryl iodides using a nickel catalyst and manganese reductant is described. The reaction conditions are mild (40 °C in MeOH, no acid or base) and an intermediate organomanganese reagent is unlikely. Functional groups tolerated include halides and pseudohalides, free and protected anilines, and a benzyl alcohol. Other activated alkynes including an amide and a ketone also reacted to form arylated products in good yields. PMID:26028781

  13. Ni(NHC)]-Catalyzed Cycloaddition of Diynes and Tropone: Apparent Enone Cycloaddition Involving an 8π Insertion

    PubMed Central

    2015-01-01

    A Ni/N-heterocyclic carbene catalyst couples diynes to the C(α)–C(β) double bond of tropone, a type of reaction that is unprecedented for metal-catalyzed cycloadditions with aromatic tropone. Many different diynes were efficiently coupled to afford [5–6–7] fused tricyclic products, while [5–7–6] fused tricyclic compounds were obtained as minor byproducts in a few cases. The reaction has broad substrate scope and tolerates a wide range of functional groups, and excellent regioselectivity is found with unsymmetrical diynes. Theoretical calculations show that the apparent enone cycloaddition occurs through a distinctive 8π insertion of tropone. The initial intramolecular oxidative cyclization of diyne produces the nickelacyclopentadiene intermediate. This intermediate undergoes an 8π insertion of tropone, and subsequent reductive elimination generates the [5–6–7] fused tricyclic product. This initial product undergoes two competing isomerizations, leading to the observed [5–6–7] and [5–7–6] fused tricyclic products. PMID:25416006

  14. Cycloadditions of 1,2,3-Triazines Bearing C5-Electron Donating Substituents: Robust Pyrimidine Synthesis.

    PubMed

    Glinkerman, Christopher M; Boger, Dale L

    2015-08-21

    The examination of the cycloaddition reactions of 1,2,3-triazines 17-19, bearing electron-donating substituents at C5, are described. Despite the noncomplementary 1,2,3-triazine C5 substituents, amidines were found to undergo a powerful cycloaddition to provide 2,5-disubstituted pyrimidines in excellent yields (42-99%; EDG = SMe > OMe > NHAc). Even select ynamines and enamines were capable of cycloadditions with 17, but not 18 or 19, to provide trisubstituted pyridines in modest yields (37-40% and 33% respectively). PMID:26172042

  15. 1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives.

    PubMed

    Meyer, Adam G; Ryan, John H

    2016-01-01

    We provide a comprehensive account of the 1,3-dipolar cycloaddition reactions of azomethine ylides with carbonyl dipolarophiles. Many different azomethine ylides have been studied, including stabilized and non-stabilized ylides. Of the carbonyl dipolarophiles, aldehydes including formaldehyde are the most studied, although there are now examples of cycloadditions with ketones, ketenes and carboxyl systems, in particular isatoic anhydrides and phthalic anhydrides. Intramolecular cycloadditions with esters can also occur under certain circumstances. The oxazolidine cycloadducts undergo a range of reactions triggered by the ring-opening of the oxazolidine ring system. PMID:27455230

  16. Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines.

    PubMed

    Lin, Tao-Yan; Zhu, Chao-Ze; Zhang, Peichao; Wang, Yidong; Wu, Hai-Hong; Feng, Jian-Jun; Zhang, Junliang

    2016-08-26

    The first rhodium-catalyzed intermolecular [3+2] cycloaddition reaction of vinyl aziridines and allenes for the synthesis of enantioenriched functionalized pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N-allenamides gave 3-methylene-pyrrolidines in high regio- and diastereoselectivity, whereas, 2-methylene-pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of allenes. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalization of the cycloadducts make this approach very practical and attractive. PMID:27485044

  17. Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis.

    PubMed

    Díaz Velázquez, Heriberto; Ruiz García, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis

    2014-12-14

    Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chemistry. Here we report a new series of water-soluble catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are additionally functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the production of triazoles with different substitution patterns. Additionally, successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calculations. PMID:25251642

  18. Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.

    PubMed

    Lepage, Mathieu L; Schneider, Jérémy P; Bodlenner, Anne; Compain, Philippe

    2015-11-01

    A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars. PMID:26439895

  19. Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents.

    PubMed

    Mei, Ruhuai; Wang, Hui; Warratz, Svenja; Macgregor, Stuart A; Ackermann, Lutz

    2016-05-10

    Cp*-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. PMID:26992149

  20. Catalytic boracarboxylation of alkynes with diborane and carbon dioxide by an N-heterocyclic carbene copper catalyst.

    PubMed

    Zhang, Liang; Cheng, Jianhua; Carry, Béatrice; Hou, Zhaomin

    2012-09-01

    By the use of an N-heterocyclic carbene copper(I) complex as a catalyst, the boracarboxylation of various alkynes (e.g., diaryl alkynes, aryl/alkyl alkynes, and phenylacetylene) with a diborane compound and carbon dioxide has been achieved for the first time, affording the α,β-unsaturated β-boralactone derivatives regio- and stereoselectively via a borylcupration/carboxylation cascade. Some important reaction intermediates were isolated and structurally characterized to clarify the reaction mechanism. PMID:22909063

  1. Phase emerging from intramonolayer cycloaddition on micro-patterned monolayer

    NASA Astrophysics Data System (ADS)

    Tajuddin, Hairul A.; Manning, Robert J.; Leggett, Graham J.; Williams, Nicholas H.

    2012-11-01

    Cu(I)-catalyzed cycloaddition between azide and acetylene, followed by hydrolysis of ester were performed on micro-patterned self-assembled monolayer to produce smaller features. The reactions were initially performed on mixed monolayers and analysed by water contact angle (CA) and confirmed by X-ray Photoelectron Spectroscopy (XPS). The contact angle measurement has shown a drastic wetting of water on the surface of mixed monolayer indicating that the terminal groups on mixed monolayer has changed into carboxylic acid and hydroxyl terminals. The reactions work in a similar way on micro-patterned SAM and analyzed by using friction force microscope. The emerging of the new lines with high friction force on the border suggested a successful intramonolayer reactions on the border of the patterned SAM.

  2. Selectivity in Ketenimine Cycloadditions. Photoelectron Hel Spectra of Ketenimines

    NASA Astrophysics Data System (ADS)

    Bernardi, Fernando; Bottoni, Andrea; Ballaglia, Arturo; Distefano, Giuseppe; Dondoni, Alessandro

    1980-05-01

    The first few bands in the photoelectron (Hel) spectra of ketenimines R1R2C-C=NR3(R1,R2=H, CH3, C5H6, CH2=CH; R3=alkyl or aryl group) are assigned to the corresponding molecular orbitals. The assignment is based on SCF-MO calculations made at three different levels (CNDO/2, ab-initio STO-3C and 4-31G) coupled with perturbational molecular orbital analyses. The π-orbitals of the unsaturated substituents are found to interact with one of the two perpendicular π-electron systems of the>C=C=N- residue, the critical factor being the position of attack of the substituent. The relevance of these results on the site selectivity observed in cycloaddition reactions of these species is discussed.

  3. Phase emerging from intramonolayer cycloaddition on micro-patterned monolayer

    SciTech Connect

    Tajuddin, Hairul A.; Manning, Robert J.; Leggett, Graham J.; Williams, Nicholas H.

    2012-11-27

    Cu(I)-catalyzed cycloaddition between azide and acetylene, followed by hydrolysis of ester were performed on micro-patterned self-assembled monolayer to produce smaller features. The reactions were initially performed on mixed monolayers and analysed by water contact angle (CA) and confirmed by X-ray Photoelectron Spectroscopy (XPS). The contact angle measurement has shown a drastic wetting of water on the surface of mixed monolayer indicating that the terminal groups on mixed monolayer has changed into carboxylic acid and hydroxyl terminals. The reactions work in a similar way on micro-patterned SAM and analyzed by using friction force microscope. The emerging of the new lines with high friction force on the border suggested a successful intramonolayer reactions on the border of the patterned SAM.

  4. Copper-catalyzed aerobic oxidative transformation of ketone-derived N-tosyl hydrazones: an entry to alkynes.

    PubMed

    Li, Xianwei; Liu, Xiaohang; Chen, Huoji; Wu, Wanqing; Qi, Chaorong; Jiang, Huanfeng

    2014-12-22

    A novel strategy involving Cu-catalyzed oxidative transformation of ketone-derived hydrazone moiety to various synthetic valuable internal alkynes and diynes has been developed. This method features inexpensive metal catalyst, green oxidant, good functional group tolerance, high regioselectivity and readily available starting materials. Oxidative deprotonation reactions were carried out to form internal alkynes and symmetrical diynes. Cross-coupling reactions of hydrazones with halides and terminal alkynes were performed to afford functionalized alkynes and unsymmetrical conjugated diynes. A mechanism proceeding through a Cu-carbene intermediate is proposed for the CC triple bond formation. PMID:25424976

  5. Computational study of a model system of enzyme-mediated [4+2] cycloaddition reaction.

    PubMed

    Gordeev, Evgeniy G; Ananikov, Valentine P

    2015-01-01

    A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reaction was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation. PMID:25853669

  6. Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones.

    PubMed

    Bentabed-Ababsa, Ghenia; Derdour, Aicha; Roisnel, Thierry; Sáez, Jose A; Domingo, Luis R; Mongin, Florence

    2008-09-01

    The [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and ketones (ethyl pyruvate, ethyl phenylglyoxylate, isatin, N-methylisatin and 5-chloroisatin) to give substituted dioxolanes and spirocyclic dioxolane indolinones was investigated. The effect of microwave irradiation on the outcome of the reaction was studied. The thermal reaction between 2,2-dicyano-3-phenyloxirane and N-methylisatin was theoretically studied using DFT methods. This reaction is a domino process that comprises two steps. The first is the thermal ring opening of the epoxide to yield a carbonyl ylide intermediate, whereas the second step is a polar [3 + 2] cycloaddition to yield the final spiro cycloadducts. The cycloaddition presents a low stereoselectivity and a large regio- and chemoselectivity. Analysis of the electrophilicity values and the Fukui functions of the reagents involved in the cycloaddition step allowed the chemical outcome to be explained. PMID:18698474

  7. Electron transfer-initiated Diels-Alder cycloadditions of 2'-hydroxychalcones.

    PubMed

    Cong, Huan; Ledbetter, Dustin; Rowe, Gerard T; Caradonna, John P; Porco, John A

    2008-07-23

    An efficient approach to cyclohexenyl chalcones employing highly electron rich 2'-hydroxychalcone dienophiles via electron transfer-initiated Diels-Alder cycloaddition is described. Using the methodology, the total synthesis of nicolaiodesin C has been accomplished. PMID:18576647

  8. Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the σ-Electron-Withdrawing Trifluoromethyl Group.

    PubMed

    Trost, Barry M; Debien, Laurent

    2015-09-16

    α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique σ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism. PMID:26291872

  9. Controlling Asymmetric Remote and Cascade 1,3-Dipolar Cycloaddition Reactions by Organocatalysis.

    PubMed

    Poulsen, Pernille H; Vergura, Stefania; Monleón, Alicia; Jørgensen, Danny Kaare Bech; Jørgensen, Karl Anker

    2016-05-25

    The regio- and stereoselective control of cycloaddition reactions to polyconjugated systems has been demonstrated by applying asymmetric organocatalysis. Reaction of 2,4-dienals with nitrones allows for a highly regio- and stereoselective 1,3-dipolar cycloaddition in the presence of an aminocatalyst. The first cycloaddition on the remote olefin can be followed either by a cascade reaction or by other selective reactions of the remaining olefin. The chiral products are obtained in good to high yields and excellent diastereo- and enantioselectivities. The remote selective concept has been extended to 2,4,6-trienals by means of a novel enantioselective triple cascade 1,3-dipolar cycloaddition reaction. The formation of chiral poly 1,3-amino alcohols is also demonstrated. PMID:27160510

  10. Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cycloaddition of 1,6-Enynes with Cyclopropylideneacetamides.

    PubMed

    Yoshizaki, Soichi; Nakamura, Yu; Masutomi, Koji; Yoshida, Tomoka; Noguchi, Keiichi; Shibata, Yu; Tanaka, Ken

    2016-02-01

    It has been established that a cationic rhodium(I)/H8-BINAP complex catalyzes the asymmetric [2 + 2 + 2] cycloaddition of 1,6-enynes with cyclopropylideneacetamides to produce spirocyclohexenes in excellent enantioselectivity with retaining cyclopropane rings. PMID:26756430

  11. The Copper-nicotinamide complex: sustainable applications in coupling and cycloaddition reactions

    EPA Science Inventory

    Crystalline copper (II)-nicotinamide complex, synthesized via simple mixing of copper chloride and nicotinamide solution at room temperature, catalyzes the C-S, C-N bond forming and cycloaddition reactions under a variety of sustainable reaction conditions.

  12. A Near-Threshold Shape Resonance in the Valence-Shell Photoabsorption of Linear Alkynes.

    PubMed

    Jacovella, U; Holland, D M P; Boyé-Péronne, S; Gans, Bérenger; de Oliveira, N; Ito, K; Joyeux, D; Archer, L E; Lucchese, R R; Xu, Hong; Pratt, S T

    2015-12-17

    The room-temperature photoabsorption spectra of a number of linear alkynes with internal triple bonds (e.g., 2-butyne, 2-pentyne, and 2- and 3-hexyne) show similar resonances just above the lowest ionization threshold of the neutral molecules. These features result in a substantial enhancement of the photoabsorption cross sections relative to the cross sections of alkynes with terminal triple bonds (e.g., propyne, 1-butyne, 1-pentyne, ...). Based on earlier work on 2-butyne [ Xu et al., J. Chem. Phys. 2012, 136, 154303 ], these features are assigned to excitation from the neutral highest occupied molecular orbital (HOMO) to a shape resonance with g (l = 4) character and approximate π symmetry. This generic behavior results from the similarity of the HOMOs in all internal alkynes, as well as the similarity of the corresponding gπ virtual orbital in the continuum. Theoretical calculations of the absorption spectrum above the ionization threshold for the 2- and 3-alkynes show the presence of a shape resonance when the coupling between the two degenerate or nearly degenerate π channels is included, with a dominant contribution from l = 4. These calculations thus confirm the qualitative arguments for the importance of the l = 4 continuum near threshold for internal alkynes, which should also apply to other linear internal alkynes and alkynyl radicals. The 1-alkynes do not have such high partial waves present in the shape resonance. The lower l partial waves in these systems are consistent with the broader features observed in the corresponding spectra. PMID:26469080

  13. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

    PubMed Central

    Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

    2015-01-01

    Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

  14. Alkyne-functionalized superstable graphitic silver nanoparticles for Raman imaging.

    PubMed

    Song, Zhi-Ling; Chen, Zhuo; Bian, Xia; Zhou, Li-Yi; Ding, Ding; Liang, Hao; Zou, Yu-Xiu; Wang, Shan-Shan; Chen, Long; Yang, Chao; Zhang, Xiao-Bing; Tan, Weihong

    2014-10-01

    Noble metals, especially gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, we report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been utilized to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-soluble, and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging. PMID:25233109

  15. Multifunctional Single-Site Catalysts for Alkoxycarbonylation of Terminal Alkynes.

    PubMed

    Chen, Xingkun; Zhu, Hejun; Wang, Wenlong; Du, Hong; Wang, Tao; Yan, Li; Hu, Xiangping; Ding, Yunjie

    2016-09-01

    A multifunctional copolymer (PyPPh2 -SO3 H@porous organic polymers, POPs) was prepared by combining acidic groups and heterogeneous P,N ligands through the copolymerization of vinyl-functionalized 2-pyridyldiphenylphosphine (2-PyPPh2 ) and p-styrene sulfonic acid under solvothermal conditions. The morphology and chemical structure of the copolymer were evaluated using a series of characterization techniques. Compared with traditional homogeneous Pd(OAc)2 /2-PyPPh2 / p-toluenesulfonic acid catalyst, the copolymer supported palladium catalyst (Pd-PyPPh2 -SO3 H@POPs) exhibited higher activity for alkoxycarbonylation of terminal alkynes under the same conditions. This phenomenon could be attributed to the synergistic effect between the single-site Pd centers, 2-PyPPh2 ligands, and SO3 H groups, the outstanding swelling properties as well as the high enrichment of the reactant concentration by the porous catalyst. In addition, the catalyst could be reused at least 4 times without any apparent loss of activity. The excellent catalytic reactivity and good recycling properties make it an attractive catalyst for industrial applications. This work paves the way for advanced multifunctional porous organic polymers as a new type of platform for heterogeneous catalysis in the future. PMID:27530651

  16. [3 + 1]- and [3 + 2]-Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides.

    PubMed

    Li, Chao; Jiang, Kun; Ouyang, Qin; Liu, Tian-Yu; Chen, Ying-Chun

    2016-06-01

    A new formal [3 + 1]-cycloaddition reaction of azaoxyallyl cation intermediates, generated in situ from α-halo hydroxamates bearing α-alkyl groups, and sulfur ylides is reported, furnishing useful β-lactams (dr >19:1) in fair to modest yields. In contrast, an unexpected formal [3 + 2]-cycloaddition reaction occurs to give γ-lactam derivatives for α-halo hydroxamates with α-aryl groups and sulfur ylides in the presence of bases. PMID:27199108

  17. A Rh(II)-catalyzed cycloaddition approach towards the synthesis of komaroviquinone

    PubMed Central

    Padwa, Albert; Chughtai, Majid J.; Boonsombat, Jutatip; Rashatasakhon, Paitoon

    2008-01-01

    Using a rhodium(II)-catalyzed cyclization/cycloaddition sequence as the key reaction step, the icetexane core of komaroviquinone was constructed by an intramolecular dipolar-cycloaddition of a carbonyl ylide dipole across a tethered π-bond. The ylide was arrived at by cyclization of a rhodium carbenoid intermediate onto a proximal ester group. Efforts towards the preparation of the required precursor for elaboration to the natural product are discussed. PMID:19461991

  18. Nazarov reactions intercepted by (4 + 3) cycloadditions with oxygen-substituted dienes.

    PubMed

    LeFort, François M; Mishra, Vinayak; Dexter, Graham D; Morgan, Timothy D R; Burnell, D Jean

    2015-06-01

    The oxyallyl cation intermediate from the Lewis acid mediated Nazarov reaction of an allenyl vinyl ketone was intercepted by acyclic, 2-silyloxy-substituted butadienes by highly regioselective (4 + 3) cycloadditions. Stereoselectivity was often modest, but in some instances steric interactions were responsible for high selectivity. The results are consistent with concerted (4 + 3) cycloadditions. In many instances, the (4 + 3) products were susceptible to fragmentation or rearrangement in the presence of the Lewis acid. PMID:25984922

  19. An Unprecedented Formal [5 + 2] Cycloaddition of Nitrones with o-Carboryne via Tandem [3 + 2] Cycloaddition/Oxygen Migration/Aromatization Sequence.

    PubMed

    Zhao, Da; Zhang, Jiji; Xie, Zuowei

    2015-11-01

    Heterocyclic skeletons are widespread among natural products as well as bioactive molecules. Cycloaddition reaction has created new opportunities to access heterocycles of great complexity due to its advantage of multiple bond formation in a single step. Here, we describe an unprecedented formal [5 + 2] cycloaddition of nitrone with o-carboryne to afford carborane-fused seven-membered heterocycles. Experimental and theoretical data suggest that a sequence of [3 + 2] cycloaddition, N-O bond cleavage, oxygen migration and rearomatization is involved in this unprecedented reaction. In this process, the nitrone moieties serve as five-atom coupling partners with both heteroatoms being incorporated into the framework of the final products. This new methodology also offers new insight into the chemistry of nitrones. PMID:26467943

  20. Stereoselectivity in Oxyallyl–Furan 4+3 Cycloadditions: Control of Intermediate Conformations and Dispersive Stabilisation with Evans’ Oxazolidinones

    PubMed Central

    Krenske, Elizabeth H.; Lohse, Andrew G.; Antoline, Jennifer E.

    2011-01-01

    Chiral oxazolidinones were previously thought to control cycloaddition stereoselectivity by steric crowding of one face of the substrate. We have discovered that in 4+3 cycloaddition reactions of oxallyls, the stereoinduction is caused instead by stabilising CH–π interactions that lead to reaction at the more crowded face of the oxazolidinone. Density functional theory calculations on the 4+3 cycloadditions of oxazolidinone-substituted oxyallyls with furans establish unexpected transition state conformations and a new explanation of selectivity. PMID:21572919

  1. Two axles threaded using a single template site: active metal template macrobicyclic [3]rotaxanes.

    PubMed

    Goldup, Stephen M; Leigh, David A; McGonigal, Paul R; Ronaldson, Vicki E; Slawin, Alexandra M Z

    2010-01-13

    Template approaches to rotaxanes normally require at least n - 1 template sites to interlock n components. Here we describe the one-pot synthesis of [3]rotaxanes in which a single metal template site induces formation of axles through each cavity of a bicyclic macrocycle. Central to the approach is that a portion of the bicyclic molecule acts as a ligand for a transition metal ion that mediates covalent bond formation through one or other macrocyclic cavity, depending on the ligand's orientation, making a mechanical bond. The ligand can then rotate so that the transition metal can catalyze the formation of a second axle through the other macrocycle. Using this strategy with the Cu(I)-catalyzed azide-alkyne cycloaddition (the CuAAC reaction) generates a [3]rotaxane with two identical axles in up to 86% yield. [3]Rotaxanes with two different axles threaded through the macrobicyclic rings can also be created using a single template site, either by having copper(I) sequentially form both mechanical bonds (via the CuAAC reaction) using different sets of building blocks for each axle or by using two different reactions catalyzed by two different metal ions: a palladium(II)-mediated alkyne homocoupling to assemble the first thread through one cavity, followed by a copper(I)-mediated CuAAC reaction to form the second axle through the other ring. PMID:19968281

  2. Catalytic Enantioselective 1,3-Dipolar Cycloadditions of Azomethine Ylides for Biology-Oriented Synthesis

    PubMed Central

    2014-01-01

    Conspectus Cycloaddition reactions are among the most powerful methods for the synthesis of complex compounds. In particular, the development and application of the 1,3-dipolar cycloaddition, an important member of this reaction class, has grown immensely due to its powerful ability to efficiently build various five-membered heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of the pyrrolidine scaffold, which is an important motif in natural products, pharmaceuticals, and biological probes. The reaction between azomethine ylides and cyclic dipolarophiles allows access to polycyclic products with considerable complexity. The extensive application of the 1,3-dipolar cycloaddition is based on the fact that the desired products can be obtained with high yield in a regio- and stereocontrolled manner. The most attractive feature of the 1,3-dipolar cycloaddition of azomethine ylides is the possibility to generate pyrrolidines with multiple stereocenters in a single step. The development of enantioselective cycloadditions became a subject of intensive and impressive studies in recent years. Among many modes of stereoinduction, the application of chiral metal–ligand complexes has emerged as the most viable option for control of enantioselectivity. In chemical biology research based on the principle of biology-oriented synthesis (BIOS), compound collections are prepared inspired by natural product scaffolds. In BIOS, biological relevance is employed as the key criterion to generate hypotheses for the design and synthesis of focused compound libraries. In particular, the underlying scaffolds of natural product classes provide inspiration for BIOS because they define the areas of chemical space explored by nature, and therefore, they can be regarded as “privileged”. The scaffolds of natural products are frequently complex and rich in stereocenters, which necessitates the development of efficient enantioselective methodologies. This Account

  3. Catalytic enantioselective 1,3-dipolar cycloadditions of azomethine ylides for biology-oriented synthesis.

    PubMed

    Narayan, Rishikesh; Potowski, Marco; Jia, Zhi-Jun; Antonchick, Andrey P; Waldmann, Herbert

    2014-04-15

    Cycloaddition reactions are among the most powerful methods for the synthesis of complex compounds. In particular, the development and application of the 1,3-dipolar cycloaddition, an important member of this reaction class, has grown immensely due to its powerful ability to efficiently build various five-membered heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of the pyrrolidine scaffold, which is an important motif in natural products, pharmaceuticals, and biological probes. The reaction between azomethine ylides and cyclic dipolarophiles allows access to polycyclic products with considerable complexity. The extensive application of the 1,3-dipolar cycloaddition is based on the fact that the desired products can be obtained with high yield in a regio- and stereocontrolled manner. The most attractive feature of the 1,3-dipolar cycloaddition of azomethine ylides is the possibility to generate pyrrolidines with multiple stereocenters in a single step. The development of enantioselective cycloadditions became a subject of intensive and impressive studies in recent years. Among many modes of stereoinduction, the application of chiral metal-ligand complexes has emerged as the most viable option for control of enantioselectivity. In chemical biology research based on the principle of biology-oriented synthesis (BIOS), compound collections are prepared inspired by natural product scaffolds. In BIOS, biological relevance is employed as the key criterion to generate hypotheses for the design and synthesis of focused compound libraries. In particular, the underlying scaffolds of natural product classes provide inspiration for BIOS because they define the areas of chemical space explored by nature, and therefore, they can be regarded as "privileged". The scaffolds of natural products are frequently complex and rich in stereocenters, which necessitates the development of efficient enantioselective methodologies. This Account highlights examples

  4. Positional effects of click cyclization on β-hairpin structure, stability, and function†

    PubMed Central

    Park, Jessica H.; Waters, Marcey L.

    2014-01-01

    The use of the copper (I)-assisted azide-alkyne cycloaddition (CuAAC, or “click” reaction) as a method of β-hairpin stabilization was investigated at several different positions to determine the impact on hairpin structure and function, including hydrogen bonded sites, non-hydrogen bonded sites, and at the peptide termini. The role of the turn sequence in the peptide and the chain length of the azied were also investigated. It was determined that the CuAAC reaction was a suitable method for locking in β-hairpin structure in peptides possessing either the type I’ turn, VNGO and the type II’ turn, VpGO. Moreover, all cyclic variants exhibited improved thermal stability and resistance to proteolysis as compared to the non-cyclic peptides, regardless of the position in the strand. Additionally, the function of the CuAAC cyclized peptides was not altered as exhibited by similar binding affinities for ATP as the WKWK peptide. These studies provided a comprehensive method for CuAAC cyclization of β-hairpin peptides, which could further be utilized in the inhibition of protein-protein and protein-nucleic acid interactions. PMID:23064223

  5. A facile copper(I)-catalyzed homocoupling of terminal alkynes to 1,3-diynes with diaziridinone under mild conditions

    PubMed Central

    Zhu, Yingguang; Shi, Yian

    2013-01-01

    A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes with diaziridinone as oxidant is described. Various terminal alkynes can be transformed into the corresponding 1,3-diynes in good yields. The reaction process is base-free, operationally simple, and amenable to gram scale. PMID:24089251

  6. Scope and limitations of the dual-gold-catalysed hydrophenoxylation of alkynes

    PubMed Central

    Gómez-Suárez, Adrián; Oonishi, Yoshihiro; Martin, Anthony R

    2016-01-01

    Summary Due to the synthetic advantages presented by the dual-gold-catalysed hydrophenoxylation of alkynes, a thorough study of this reaction was carried out in order to fully define the scope and limitations of the methodology. The protocol tolerates a wide range of functional groups, such as nitriles, ketones, esters, aldehydes, ketals, naphthyls, allyls or polyphenols, in a milder and more efficient manner than the previously reported methodologies. We have also identified that while we are able to use highly steric hindered phenols, small changes on the steric bulk of the alkynes have a dramatic effect on the reactivity. More importantly, we have observed that the use of substrates that facilitate the formation of diaurated species such as gem-diaurated or σ,π-digold–acetylide species, hinder the catalytic activity. Moreover, we have identified that the use of directing groups in unsymmetrical alkynes can help to achieve high regioselectivity in the hydrophenoxylation. PMID:26977176

  7. A genetically encoded alkyne directs palladium-mediated protein labeling on live mammalian cell surface.

    PubMed

    Li, Nan; Ramil, Carlo P; Lim, Reyna K V; Lin, Qing

    2015-02-20

    The merging of site-specific incorporation of small bioorthogonal functional groups into proteins via amber codon suppression with bioorthogonal chemistry has created exciting opportunities to extend the power of organic reactions to living systems. Here we show that a new alkyne amino acid can be site-selectively incorporated into mammalian proteins via a known orthogonal pyrrolysyl-tRNA synthetase/tRNACUA pair and directs an unprecedented, palladium-mediated cross-coupling reaction-driven protein labeling on live mammalian cell surface. A comparison study with the alkyne-encoded proteins in vitro indicated that this terminal alkyne is better suited for the palladium-mediated cross-coupling reaction than the copper-catalyzed click chemistry. PMID:25347611

  8. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    PubMed Central

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  9. Scope and limitations of the dual-gold-catalysed hydrophenoxylation of alkynes.

    PubMed

    Gómez-Suárez, Adrián; Oonishi, Yoshihiro; Martin, Anthony R; Nolan, Steven P

    2016-01-01

    Due to the synthetic advantages presented by the dual-gold-catalysed hydrophenoxylation of alkynes, a thorough study of this reaction was carried out in order to fully define the scope and limitations of the methodology. The protocol tolerates a wide range of functional groups, such as nitriles, ketones, esters, aldehydes, ketals, naphthyls, allyls or polyphenols, in a milder and more efficient manner than the previously reported methodologies. We have also identified that while we are able to use highly steric hindered phenols, small changes on the steric bulk of the alkynes have a dramatic effect on the reactivity. More importantly, we have observed that the use of substrates that facilitate the formation of diaurated species such as gem-diaurated or σ,π-digold-acetylide species, hinder the catalytic activity. Moreover, we have identified that the use of directing groups in unsymmetrical alkynes can help to achieve high regioselectivity in the hydrophenoxylation. PMID:26977176

  10. Pyrrolidine synthesis via palladium-catalyzed trimethylenemethane cycloaddition and related studies

    SciTech Connect

    Marrs, C.M.

    1992-01-01

    The palladium catalyzed trimethylenemethane cycloaddition has been extended to the synthesis of pyrrolidines and azepines. In contrast to previous attempts with N-alkyl and N-aryl imine, successful cycloadditions were recorded with several aromatic and aliphatic electron-deficient imines. Sulfonimines were found to be excellent acceptors, yielding pyrrolidine cycloadducts in excellent yields. Aromatic sulfonimines were observed to undergo cycloaddition very rapidly at or below room temperature. Some aliphatic nitrimine and N-phenyl, C-carbalkoxy imines were also found to be useful acceptors. Azepines were obtained from the cycloaddition of cisoid lockeed [alpha],[beta] unsaturated sulfonimines. In order to support the cycloaddition studies, a novel synthetic method was developed for the synthesis of sulfonimines. bis(Toluene-sulfonylimido)tellurium, Te(=N-Ts)[sub 2], generated from tellurium metal and anhydrous chloramine-t, was found to convert both aromatic and aliphatic aldehydes into the corresponding sulfonimines. Chiral ligands were examined in this cyclization and an enantiomeric excess of 35% was achieved with Hayashi's bidentate ferrocenyl ligand (BPFA). In support of this effort, the total synthesis of [+-] nicotine was accomplished in seven steps starting from pyridine 3-carboxaldehyde using these methodologies in order to verify the enantiomeric excess. Finally, the trimethylenemethane cycloaddition was examined with tropone irontricarbonyl complex. A novel [5+3] cycloaddition was observed to proceed in good yield, which upon decomplexation from the iron tricarbonyl moiety yielded the tricyclo[3.2.0] system. The scope and generality were briefly examined. Extended Huekel calculations were performed in order to help rationalize the unexpected regiochemistry.

  11. Regioselectivity and Enantioselectivity in Nickel-Catalysed Reductive Coupling Reactions of Alkynes

    PubMed Central

    Moslin, Ryan M.; Miller-Moslin, Karen; Jamison, Timothy F.

    2011-01-01

    Nickel-catalysed reductive coupling reactions of alkynes have emerged as powerful synthetic tools for the selective preparation of functionalized alkenes. One of the greatest challenges associated with these transformations is control of regioselectivity. Recent work from our laboratory has provided an improved understanding of several of the factors governing regioselectivity in these reactions, and related studies have revealed that the reaction mechanism can differ substantially depending on the ligand employed. A discussion of stereoselective transformations and novel applications of nickel catalysis in coupling reactions of alkynes is also included. PMID:17971951

  12. Supported gold nanoparticles catalyzed cis-selective semihydrogenation of alkynes using ammonium formate as the reductant.

    PubMed

    Liang, Shengzong; Hammond, Gerald B; Xu, Bo

    2016-05-21

    TiO2 supported gold nanoparticles with low loading (0.5 mol%) are able to semihydrogenate non-fluorinated and gem-difluorinated alkynes to cis-alkenes with high selectivity, using cost-effective and easy-to-handle ammonium formate as the reductant. No over-reduction was observed. The good recyclability of Au/TiO2 allows for "green" semireduction of alkynes. A difluorinated pyran and α,β-unsaturated δ-lactone were easily prepared from the obtained gem-difluoro alkene building blocks. PMID:27063707

  13. Development of Zn-ProPhenol-Catalyzed Asymmetric Alkyne Addition: Synthesis of Chiral Propargylic Alcohols

    PubMed Central

    Trost, Barry M.; Bartlett, Mark J.; Weiss, Andrew H.; von Wangelin, Axel Jacobi; Chan, Vincent S.

    2013-01-01

    The development of a general and practical zinc-catalyzed enantioselective alkyne addition methodology is reported. Commercially available ProPhenol ligand (1) has facilitated the addition of a wide range of zinc alkynylides to aryl, aliphatic and α,β-unsaturated aldehydes in high yield and enantioselectivity. New insights into the mechanism of this reaction have resulted in a significant reduction in reagent stoichiometry, enabling the use of precious alkynes and avoiding the use of excess dimethylzinc. The enantioenriched propargylic alcohols from this reaction serve as versatile synthetic intermediates and have enabled efficient syntheses of several complex natural products. PMID:23097281

  14. Recent Developments in Metal-Catalyzed Additions of Oxygen Nucleophiles to Alkenes and Alkynes

    NASA Astrophysics Data System (ADS)

    Hintermann, Lukas

    Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonactivated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes.

  15. Clickable enzyme-linked immunosorbent assay.

    PubMed

    Canalle, Luiz A; Vong, TuHa; Adams, P Hans H M; van Delft, Floris L; Raats, Jos M H; Chirivi, Renato G S; van Hest, Jan C M

    2011-10-10

    Click chemistry is explored as a potential cost-effective and selective immobilization method for the production of an enzyme-linked immunosorbent assay (ELISA). Coatings were formulated containing either a terminal alkyne or a bicyclo[6.1.0]non-4-yne (BCN) chemical handle, and a diagnostic peptide was subsequently immobilized onto these coatings by the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) or copper-free strain-promoted azide-alkyne 1,3-dipolar cycloaddition (SPAAC), respectively. The terminal alkyne-containing coating showed high background levels in subsequent ELISA's due to the copper catalyst used in the immobilization step. The BCN-containing coating, however, was successfully employed and presents a cost-effective alternative to existing (strept)avidin-biotin immobilization methods. This technology was illustrated with an ELISA used for the diagnosis of rheumatoid arthritis (RA) but could be easily applied to a wide range of diagnostic tests. PMID:21866934

  16. Unprecedented Intramolecular [4 + 2]-Cycloaddition between a 1,3-Diene and a Diazo Ester.

    PubMed

    Qiu, Huang; Srinivas, Harathi D; Zavalij, Peter Y; Doyle, Michael P

    2016-02-17

    Diazo compounds that are well-known to undergo [3 + 2]-cycloaddition provide the first examples of the previously unknown [4 + 2]-cycloaddition with dienes that occur thermally under mild conditions and in high yields. Reactions are initiated from reactants prepared from propargyl aryldiazoacetates that undergo gold(I)-catalyzed rearrangement to activated 1,3-dienyl aryldiazoacetates. These reactions proceed to mixtures of both [4 + 2]-cycloaddition and the 1,3-dienyl aryldiazoacetate after long reaction times. At short reaction times, however, both E- and Z-1,3-dienyl aryldiazoacetates are formed and, after isolation, thermal reactions with the E-isomers form the products from [4 + 2]-cycloaddition with ΔH(‡)298 = 15.6 kcal/mol and ΔS(‡)298 = -27.3 cal/(mol·°C). The Z-isomer is inert to [4 + 2]-cycloaddition under these conditions. The Hammett relationships from aryl-substituted diazo esters (ρ = +0.89) and aryl-substituted dienes (ρ = -1.65) are consistent with the dipolar nature of this transformation. PMID:26794409

  17. Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin.

    PubMed

    Ó Proinsias, Keith; Ociepa, Michał; Pluta, Katarzyna; Chromiński, Mikołaj; Nexo, Ebba; Gryko, Dorota

    2016-06-01

    The binding of vitamin B12 derivatives to human B12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized and its limitations examined. The resulting derivatives, particularly those bearing terminal alkyne and azide groups, were isolated and used in copper-catalyzed alkyne-azide cycloaddition reactions (CuAAC). Their sensitivity towards light revealed their potential as photocleavable molecules. The binding abilities of selected derivatives were examined and compared with cyanocobalamin. The interaction of the alkylated derivatives with haptocorrin was less affected than the interaction with intrinsic factor. Furthermore, the configuration of the phosphate moiety was irrelevant to the binding process. PMID:27120016

  18. Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide.

    PubMed

    Rubio, Noelia; Mei, Kuo-Ching; Klippstein, Rebecca; Costa, Pedro M; Hodgins, Naomi; Wang, Julie Tzu-Wen; Festy, Frederic; Abbate, Vincenzo; Hider, Robert C; Chan, Ka Lung Andrew; Al-Jamal, Khuloud T

    2015-09-01

    Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol-ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID:26278410

  19. Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide

    PubMed Central

    2015-01-01

    Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol–ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID:26278410

  20. Synthesis of double-clickable functionalised graphene oxide for biological applications† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc05412e Click here for additional data file.

    PubMed Central

    Mei, Kuo-Ching; Rubio, Noelia; Costa, Pedro M.; Kafa, Houmam; Abbate, Vincenzo; Festy, Frederic; Bansal, Sukhvinder S.; Hider, Robert C.

    2015-01-01

    Azide- and alkyne-double functionalised graphene oxide (Click2 GO) was synthesised and characterised with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and Raman spectroscopy. Fourteen-percentage increase in azide content was found, after pre-treatment of GO with meta-chloroperoxybenzoic acid (mCPBA), determined with elemental analysis. No effect on A549 cell viability was found, up to 100 μg mL–1 and 72 h of incubation, determined with the modified lactate dehydrogenase (mLDH) assay. Two sequential copper(i) catalysed azide–alkyne cycloaddition (CuAAC) reactions were performed to conjugate the propargyl-modified blood–brain barrier targeting peptide Angiopep-2, and a bis-azide polyethylene glycol (M W = 3500), to the Click2 GO. The final conjugate was characterised with ATR-FTIR and TGA. PMID:26295072

  1. Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

    PubMed

    Pyta, Krystian; Blecha, Marietta; Janas, Anna; Klich, Katarzyna; Pecyna, Paulina; Gajecka, Marzena; Przybylski, Piotr

    2016-09-01

    Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds. PMID:27469129

  2. Storable N-Phenylcarbamate Palladacycles for Rapid Functionalization of An Alkyne-Encoded Protein

    PubMed Central

    Cheng, Gang; Lim, Reyna K. V.; Ramil, Carlo P.

    2014-01-01

    Here we report the synthesis of storable N-phenyl-carbamate palladacycles that showed robust reactivity in the cross-coupling reaction with an alkyne-encoded protein with second-order rate constantapproaching 19 770 ± 930 M−1 s−1. PMID:25140915

  3. Copper(I)-Catalyzed Radical Addition of Acetophenones to Alkynes in Furan Synthesis.

    PubMed

    Manna, Srimanta; Antonchick, Andrey P

    2015-09-01

    A synthesis of multisubstituted furans from readily available acetophenones and electron-deficient alkynes via direct C(sp(3))-H bond functionalization under radical reaction conditions is described. The developed transformation is catalyzed by copper(I) salts using di-tert-butyl peroxide as an external oxidant. This method offers an efficient access to biologically important scaffolds from simple compounds. PMID:26277912

  4. Magnetically Recoverable Supported Ruthenium Catalyst for Hydrogenation of Alkynes and Transfer Hydrogenation of Carbonyl Compounds

    EPA Science Inventory

    A ruthenium (Ru) catalyst supported on magnetic nanoparticles (NiFe2O4) has been successfully synthesized and used for hydrogenation of alkynes at room temperature as well as transfer hydrogenation of a number of carbonyl compounds under microwave irradiation conditions. The cata...

  5. Cobalt-Catalyzed Alkyne Hydrosilylation and Sequential Vinylsilane Hydroboration with Markovnikov Selectivity.

    PubMed

    Zuo, Ziqing; Yang, Ji; Huang, Zheng

    2016-08-26

    A pyridinebis(oxazoline) cobalt complex is a very efficient precatalyst for the hydrosilylation of terminal alkynes with Ph2 SiH2 , providing α-vinylsilanes with high (Markovnikov) regioselectivity and broad functional-group tolerance. The vinylsilane products can be further converted into geminal borosilanes through Markovnikov hydroboration with pinacolborane and a bis(imino)pyridine cobalt catalyst. PMID:27479796

  6. Cu(I)-catalyzed direct addition and asymmetric addition of terminal alkynes to imines

    PubMed Central

    Wei, Chunmei; Mague, Joel T.; Li, Chao-Jun

    2004-01-01

    A Cu(I)-catalyzed direct addition of alkynes to imines was developed. The process is simple and provides a diverse range of propargylamines in high enantiomeric excess and good yield both in water and in toluene. The absolute configuration of such addition products has been determined by x-ray crystallography. PMID:15067132

  7. Ancillary ligand-free copper catalysed hydrohydrazination of terminal alkynes with NH2NH2.

    PubMed

    Peltier, Jesse L; Jazzar, Rodolphe; Melaimi, Mohand; Bertrand, Guy

    2016-02-14

    An efficient and selective Cu-catalysed hydrohydrazination of terminal alkynes with parent hydrazine is reported. The methodology tolerates a broad range of functional groups, allows for the synthesis of symmetrical and unsymmetrical azines, and can be extended to hydrazine derivatives and amines. PMID:26757745

  8. Vapor Phase Alkyne Coating of Pharmaceutical Excipients: Discrimination Enhancement of Raman Chemical Imaging for Tablets.

    PubMed

    Yamashita, Mayumi; Sasaki, Hiroaki; Moriyama, Kei

    2015-12-01

    Raman chemical imaging has become a powerful analytical tool to investigate the crystallographic characteristics of pharmaceutical ingredients in tablet. However, it is often difficult to discriminate some pharmaceutical excipients from each other by Raman spectrum because of broad and overlapping signals, limiting their detailed assessments. To overcome this difficulty, we developed a vapor phase coating method of excipients by an alkyne, which exhibits a distinctive Raman signal in the range of 2100-2300 cm(-1) . We found that the combination of two volatile reagents, propargyl bromide and triethylamine, formed a thin and nonvolatile coating on the excipient and observed the Raman signal of the alkyne at the surface. We prepared alkyne-coated cellulose by this method and formed a tablet. The Raman chemical imaging of the tablet cross-section using the alkyne peak area intensity of 2120 cm(-1) as the index showed a much clearer particle image of cellulose than using the peak area intensity of 1370 cm(-1) , which originated from the cellulose itself. Our method provides an innovative technique to analyze the solid-state characteristics of pharmaceutical excipients in tablets. PMID:26343262

  9. Ruthenium-Catalyzed C-H Alkynylation of Aromatic Amides with Hypervalent Iodine-Alkyne Reagents.

    PubMed

    Boobalan, Ramadoss; Gandeepan, Parthasarathy; Cheng, Chien-Hong

    2016-07-15

    An efficient C-H activation method for the ortho alkynylation of aromatic N-methoxyamides with hypervalent iodine-alkyne reagent using a ruthenium catalyst is described. The reaction proceeds under mild reaction conditions with broad substrate scope. A possible catalytic cycle involving a ruthenium carboxylate assisted C-H bond cleavage is proposed from the preliminary mechanistic evidence. PMID:27357724

  10. A HIGHLY STEREOSELECTIVE, NOVEL COUPLING REACTION BETWEEN ALKYNES WITH ALDEHYDES. (R828129)

    EPA Science Inventory

    In the presence of indium triflate or gallium chloride, a novel coupling between internal alkynes and aldehydes occurred to give unsaturated ketones and [4+1] annulation products.


    Graphical Abstrac...

  11. Electrocatalytic activities of alkyne-functionalized copper nanoparticles in oxygen reduction in alkaline media

    NASA Astrophysics Data System (ADS)

    Liu, Ke; Song, Yang; Chen, Shaowei

    2014-12-01

    Stable alkyne-capped copper nanoparticles were prepared by chemical reduction of copper acetate with sodium borohydride in the presence of alkyne ligands. Transmission electron microscopic measurements showed that nanoparticles were well dispersed with a diameter in the range of 4-6 nm. FTIR and photoluminescence spectroscopic measurements confirmed the successful attachment of the alkyne ligands onto the nanoparticle surface most likely forming Cu-Ctbnd interfacial bonds. XPS measurements indicated the formation of a small amount of CuO in the nanoparticles with a satellite peak where the binding energy red-shifted with increasing Cu(II) concentration. Cu2O was also detected in the nanoparticles. Similar results were observed with commercial CuO nanoparticles. Electrochemical studies showed that the as-prepared alkyne-capped copper nanoparticles exhibited apparent electrocatalytic activity in oxygen reduction in alkaline media, a performance that was markedly better than those reported earlier with poly- or single-crystalline copper electrodes; and the fraction of peroxides in the final products decreased with decreasing concentration of oxide components in the nanoparticles.

  12. Aerobic Oxidation in Nanomicelles of Aryl Alkynes, in Water at Room Temperature**

    PubMed Central

    Handa, Sachin; Fennewald, James C.; Rainey, Shane

    2014-01-01

    On the basis of the far higher solubility of oxygen gas inside the hydrocarbon core of nanomicelles, metal and peroxide free aerobic oxidation of aryl alkynes has been achieved in water at room temperature. Many examples are offered that illustrate broad functional group tolerance. The overall process is environmentally friendly, documented by the associated low E Factors. PMID:24616243

  13. Conversion of unsaturated alcohols into functionalized tetrahydrofurans and tetrahydropyrans via nitrile oxide dipolar cycloadditions

    SciTech Connect

    Hassner, A.; Murthy, K.S.K. ); Padwa, A.; Dean, D.C.; Schoffstall, A.M. ); Chiacchio, U. )

    1989-10-27

    The intramolecular nitrile oxide cycloaddition (INOC) of a series of unsaturated oximino ethers has been investigated. The synthesis of the olefinic nitrile oxides involves treating an unsaturated alcohol with a {alpha}-bromoalkanal O-(trimethylsilyl)oxime in the presence of fluoride ion followed by subsequent sodium hypochlorite oxidation. The nitrile oxides were not isolated but spontaneously underwent intramolecular cycloaddition to give fused five- and six-membered ring ethers. The preferred stereoisomer in the formation of the five-membered ring ethers is trans, whereas in the six-membered ring ethers the cis isomer predominates. MM2 calculations help rationalize the observed stereoselectivity. The ratio of diastereomeric products from the INOC reaction appears to correlate with product stabilities. Simple heating of some of the oximino ethers led to intramolecular cycloaddition. The ring closure apparently proceeds subsequent to a tautomeric equilibration of the oxime with a transient nitrone which is trapped by the neighboring {pi}-bond.

  14. Intramolecular nitrone dipolar cycloadditions: control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids.

    PubMed

    Hodges, Alastair J; Adams, Joseph P; Bond, Andrew D; Holmes, Andrew B; Press, Neil J; Roughley, Stephen D; Ryan, John H; Saubern, Simon; Smith, Catherine J; Turnbull, Michael D; Newton, Annabella F

    2012-12-01

    The intramolecular nitrone dipolar cycloaddition of in situ-generated nitrones such as compound 26 has been used for the synthesis of cyclic isoxazolidines 27 and 29. The regioselectivity of the intramolecular cycloaddition depends on the nature of the terminal substituent on the dipolarophile. The influence of the substituent on the regioselectivity of the cycloaddition has been examined using several model systems and two methods of nitrone formation. These studies demonstrated that the cyano-substituent plays a special role in favouring the formation of the 6,6,5-ring fused adduct 27 under thermodynamically controlled conditions. The utility of the cyclo-adduct 57 (see Scheme 12) as a precursor for the naturally occurring histrionicotoxins is illustrated by the synthesis of three "unsymmetrical" (i.e. with each side chain bearing different functional groups) members of the histrionicotoxin family HTX-259A, HTX-285C and HTX-285E (2, 3 and 4 respectively). PMID:23051904

  15. Covalently crosslinked diels-alder polymer networks.

    SciTech Connect

    Bowman, Christopher; Adzima, Brian J.; Anderson, Benjamin John

    2011-09-01

    This project examines the utility of cycloaddition reactions for the synthesis of polymer networks. Cycloaddition reactions are desirable because they produce no unwanted side reactions or small molecules, allowing for the formation of high molecular weight species and glassy crosslinked networks. Both the Diels-Alder reaction and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) were studied. Accomplishments include externally triggered healing of a thermoreversible covalent network via self-limited hysteresis heating, the creation of Diels-Alder based photoresists, and the successful photochemical catalysis of CuAAC as an alternative to the use of ascorbic acid for the generation of Cu(I) in click reactions. An analysis of the results reveals that these new methods offer the promise of efficiently creating robust, high molecular weight species and delicate three dimensional structures that incorporate chemical functionality in the patterned material. This work was performed under a Strategic Partnerships LDRD during FY10 and FY11 as part of a Sandia National Laboratories/University of Colorado-Boulder Excellence in Science and Engineering Fellowship awarded to Brian J. Adzima, a graduate student at UC-Boulder. Benjamin J. Anderson (Org. 1833) was the Sandia National Laboratories point-of-contact for this fellowship.

  16. Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and heterocycles.

    PubMed

    Thakur, Ashish; Louie, Janis

    2015-08-18

    Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles. PMID:26200651

  17. Mechanism and selectivity of N-triflylphosphoramide catalyzed (3(+) + 2) cycloaddition between hydrazones and alkenes.

    PubMed

    Hong, Xin; Küçük, Hatice Başpınar; Maji, Modhu Sudan; Yang, Yun-Fang; Rueping, Magnus; Houk, K N

    2014-10-01

    Brønsted acid catalyzed (3(+) + 2) cycloadditions between hydrazones and alkenes provide a general approach to pyrazolidines. The acidity of the Brønsted acid is crucial for the catalytic efficiency: the less acidic phosphoric acids are ineffective, while highly acidic chiral N-triflylphosphoramides are very efficient and can promote highly enantioselective cycloadditions. The mechanism and origins of catalytic efficiencies and selectivities of these reactions have been explored with density functional theory (M06-2X) calculations. Protonation of hydrazones by N-triflylphosphoramide produces hydrazonium-phosphoramide anion complexes. These ion-pair complexes are very reactive in (3(+) + 2) cycloadditions with alkenes, producing pyrazolidine products. Alternative 1,3-dipolar (3 + 2) cycloadditions with the analogous azomethine imines are much less favorable due to the endergonic isomerization of hydrazone to azomethine imine. With N-triflylphosphoramide catalyst, only a small distortion of the ion-pair complex is required to achieve its geometry in the (3(+) + 2) cycloaddition transition state. In contrast, the weak phosphoric acid does not protonate the hydrazone, and only a hydrogen-bonded complex is formed. Larger distortion energy is required for the hydrogen-bonded complex to achieve the "ion-pair" geometry in the cycloaddition transition state, and a significant barrier is found. On the basis of this mechanism, we have explained the origins of enantioselectivities when a chiral N-triflylphosphoramide catalyst is employed. We also report the experimental studies that extend the substrate scope of alkenes to ethyl vinyl ethers and thioethers. PMID:25226575

  18. Ion radical cycloadditions and the synthesis of novel, electron-rich polymer structures

    NASA Astrophysics Data System (ADS)

    Roh, Yeonsuk

    The aminium salt initiated cation radical chain cycloaddition polymerization of various oxygenated difunctional monomers is investigated in order to minimize a limiting factor, a competing carbocation pathway, by applying a dichloromethane/water binary solvent mixture. Polymerizations have also been initiated by electrochemical oxidation and photosensitized electron transfer. The synthesis of cation radical cycloaddition polymers of difunctional carbazole monomers which contain reactive trans-1-propenyl groups for polymerization in the N-, 3- or 6-positions of carbazole, is presented. All polymers containing carbazole units in the polymer main chain show good solubility in halogenated organic solvents, high molecular weights, and high thermal stabilities. The reaction appears to proceed via a highly efficient cation radical chain mechanism which circumvents the usual hole transfer step of the propagation cycle. This polymerization represents the first observation of direct cation radical Diels-Alder cycloaddition polymerization and affords a novel polymer structure. The cation radical Diels-Alder cycloadditions of monofunctional, highly electron-rich substrates such as N-(trans-1-propenyl)carbazoles and N-phenyl-3-(trans-1-propenyl)carbazole to generate monomers of interest in connection with ring-opening metathesis polymerization are also presented. The cycloadditions of various electron-rich monomers to 1,3-cyclopentadiene efficiently generate norbornene monomers, which readily undergo ring-opening metathesis polymerization to yield electron rich polymers. Both ring-opened homopolymers and copolymers containing carbazole groups are synthesized. In addition, investigations of photorefractive effects resulting from a combination of photoconductive and electro-optic effects (change in refractive index in response to an electric field) in composites which utilize new carbazole-containing polymers as charge transport components are carried out, and their

  19. Base-controlled [3+3] cycloaddition of isoquinoline N-oxides with azaoxyallyl cations.

    PubMed

    An, Yuanyuan; Xia, Hongguang; Wu, Jie

    2016-08-16

    A base-controlled [3+3] cycloaddition reaction of isoquinoline N-oxides with azaoxyallyl cations is developed. 1,11b-dihydro-[1,2,4]oxadiazino[3,2-a]isoquinolin-2(3H)-ones are obtained when isoquinoline N-oxides are treated with α-halohydroxamates in the presence of sodium carbonate, while 2-(isoquinolin-1-yloxy)acetamides are unexpectedly produced when the base is changed to cesium carbonate. This transformation proceeds through an azaoxyallyl cation generated in situ from α-bromohydroxamate, and the [3+3] cycloaddition reaction is the key step for the final outcome. PMID:27484327

  20. N-heterocyclic phosphenium cations: syntheses and cycloaddition reactions.

    PubMed

    Caputo, Christine A; Price, Jacquelyn T; Jennings, Michael C; McDonald, Robert; Jones, Nathan D

    2008-07-14

    A series of trifluoromethanesulfonate (OTf) salts of N-heterocyclic phospheniums (NHP) bearing phenyl (1a), para-methoxyphenyl (1b), 2,6-diisopropylphenyl (1c) and mesityl (1d) substituents is reported. The compounds are made by a modification to a literature procedure that improves the overall yields for and by 15 and 23%, respectively. Two unwanted side-products in the synthesis of , the diammonium salt, [(2,6-iPr-C6H3)N(H)2CH2CH2N(H)2(2,6-iPr-C6H3)]Cl2 (4) and the bisphosphine (2,6-iPr-C6H3)N(PCl2)CH2CH2N(PCl2)(2,6-iPr-C6H3) (5), are crystallographically characterized, as is the intermediate cyclic chlorophosphine, C1PN(4-OMe-C6H4)CH2CH2N(4-OMe-C6H4) (3b). The phenyl-substituted NHP is fully characterized, including by X-ray crystallography, for the first time; this compound contains a short P-O contact of 2.1850(14) A. Cycloaddition reactions of with 2,3-dimethyl-1,3-butadiene give the expected spirocyclic phospholeniums, 7,8-dimethyl-1,4-diaryl-1,4-diaza-5-phopshoniaspiro[4.4]non-7-ene, as their OTf salts (6a-d), while reactions with N,N'-dimesityl-1,4-diaza-1,3-butadiene give, except in the case of , which is too bulky to react, the aza analogues, 1,4-dimesityl-6,9-diaryl-1,4,6,9-tetraaza-5-phosphoniaspiro[4.4]non-2-ene (7a, 7b and 7d). The sterically congested is in thermal equilibrium with and free diazadiene, and undergoes a substitution reaction with 2,3-dimethyl-1,3-butadiene to give . PMID:18580983

  1. Annulation of thioimidates and vinyl carbodiimides to prepare 2-aminopyrimidines, competent nucleophiles for intramolecular alkyne hydroamination. Synthesis of (-)-crambidine.

    PubMed

    Perl, Nicholas R; Ide, Nathan D; Prajapati, Sudeep; Perfect, Hahdi H; Durón, Sergio G; Gin, David Y

    2010-02-17

    A convergent synthesis of (-)-crambidine is reported. The sequence capitalizes on two novel key transformations, including a [4+2] annulation of thioimidates with vinyl carbodiimides and an alkyne hydroamination employing 2-aminopyrimidine nucleophiles. PMID:20095555

  2. Cu-Catalyzed Alkynylation of Unactivated C(sp(3))-X Bonds with Terminal Alkynes through Directing Strategy.

    PubMed

    Luo, Fei-Xian; Xu, Xing; Wang, Ding; Cao, Zhi-Chao; Zhang, Yun-Fei; Shi, Zhang-Jie

    2016-05-01

    In this letter, we report an efficient and concise protocol for Cu-catalyzed cross-coupling of unactivated alkyl halides/peusudohalides with terminal alkynes to afford internal alkynes with the assistance of various amides as directing groups. Different alkyl halides/pseudohalides exhibited excellent reactivities, and the inactivated alkyl chlorides and sulfonates showed better reactivity than bromides/iodides. This is the first successful example to apply alkyl chlorides and sulfonates directly in cross-coupling with terminal alkynes in the absence of any additives. A Cu catalyst was found to be more effective than other transition metal catalysts. This reaction also exhibited a broad substrate scope with respect to terminal alkynes. PMID:27074521

  3. Ligand-Enabled, Copper-Catalyzed Regio- and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes.

    PubMed

    Itoh, Taisuke; Shimizu, Yohei; Kanai, Motomu

    2016-06-22

    We report the first copper-catalyzed regio- and stereoselective borylalkylation of dialkylsubstituted internal alkynes with bis(pinacolato)diboron and alkyl halides. A catalytically generated borylcopper species containing a novel π-accepting N-heterocyclic carbene ligand chemoselectively reacted with unactivated internal alkynes over alkyl halides. The intermediate alkenylcopper species subsequently reacted with alkyl halides, affording the desired products. The copper catalyst differentiated steric demands between the two aliphatic substituents on the C≡C triple bond of the alkyne substrates to exhibit high regioselectivity from a wide range of alkyne/alkyl halide combinations. This method is useful for the straightforward synthesis of trialkylsubstituted alkenylboronates, i.e., versatile precursors for tetrasubstituted alkenes containing three or four different alkylsubstituents, which are difficult to synthesize by other methods. PMID:27269988

  4. Double hydrophosphination of alkynes promoted by rhodium: the key role of an N-heterocyclic carbene ligand.

    PubMed

    Di Giuseppe, Andrea; De Luca, Roberto; Castarlenas, Ricardo; Pérez-Torrente, Jesús J; Crucianelli, Marcello; Oro, Luis A

    2016-04-25

    The regioselective double hydrophosphination of alkynes mediated by rhodium catalysts is presented. The distinctive stereoelectronic properties of the NHC ligand prevent the catalyst deactivation by diphosphine coordination thereby allowing for the closing of a productive catalytic cycle. PMID:27022648

  5. Assembly of the Isoindolinone Core of Muironolide A by Asymmetric Intramolecular Diels-Alder Cycloaddition

    PubMed Central

    Flores, Beatris; Molinski, Tadeusz F.

    2011-01-01

    The hexahydro-1H-isoindolin-1-one core of muironolide A was prepared by asymmetric intramolecular Diels Alder cycloaddition using a variant of the MacMillan organocatalyst which sets the C4,C5 and C11 stereocenters. PMID:21751773

  6. Nickel-catalyzed [3+1+1] cycloaddition reactions of alkenyl Fischer carbene complexes with methylenecyclopropanes.

    PubMed

    Kamikawa, Ken; Shimizu, Yasunori; Takemoto, Shin; Matsuzaka, Hiroyuki

    2006-08-31

    Methylenecyclopentanones were synthesized by the nickel-catalyzed [3+1+1] cycloaddition reactions of alkenyl Fischer carbene complexes with methylenecyclopropanes. The methylenecyclopropane was transformed into the C(2)-symmetric bis-cyclopentapyridazine derivative by reacting with p-toluenesulfonyl hydrazine. PMID:16928061

  7. 3+2-Dipolar cycloaddition of dianhydrohexitol azidoderivatives with N-arylmaleimides

    NASA Astrophysics Data System (ADS)

    Gella, I. M.; Babak, N. L.; Drushlyak, T. G.; Shishkina, S. V.; Musatov, V. I.; Lipson, V. V.

    2015-11-01

    Dianhydrohexitol azides dipolar 3+2 cycloaddition with N-arylmaleimides has been studied with NMR (1H and 13C, COSY, NOESY and HSQC) and X-ray analysis. In spite of low asymmetrical induction in this reaction, diastereomerically pure products have been obtained. These products are interesting over their structural similarity to griseolic acid derivatives and dihydropyrrolotriazoles, significant for pharmaceutics.

  8. Computational Study of a Model System of Enzyme-Mediated [4+2] Cycloaddition Reaction

    PubMed Central

    2015-01-01

    A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reac-tion was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation. PMID:25853669

  9. A Palladium-Catalyzed Vinylcyclopropane (3 + 2) Cycloaddition Approach to the Melodinus Alkaloids

    PubMed Central

    Goldberg, Alexander F. G.; Stoltz, Brian M.

    2011-01-01

    A palladium-catalyzed (3 + 2) cycloaddition of a vinylcyclopropane and a β-nitrostyrene are employed to rapidly assemble the cyclopentane core of the Melodinus alkaloids. The ABCD ring system of the natural product family is prepared in six steps from commercially available materials. PMID:21786746

  10. Cycloaddition-Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones.

    PubMed

    Padwa, Albert; Brodney, Michael A.; Satake, Kyosuke; Straub, Christopher S.

    1999-06-25

    A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The reaction rate and product yield were found to be markedly dependent upon the electronic properties of the alkenyl pi-bond. 2-[2-(tert-Butoxycarbonylfuran-2-yl-amino)ethyl]acrylic acid methyl ester was synthesized from 3-chlorocarbonyl-but-3-enoic acid methyl ester. Thermolysis of the carbomethoxy activated furanamide occurred at 80 degrees C to produce a rearranged hexahydroindolinone. When Me(3)Al or (MeO)(3)Al was used as a Lewis acid to promote the cycloaddition, a rearranged alcohol was obtained. The initially formed [4 + 2] cycloadduct undergoes ring opening in the presence of the Lewis acid, and the resulting aluminum intermediate delivers the substituent group from the same face as the neighboring oxygen to ultimately furnish a rearranged cis-alcohol. In contrast to this result, a mixture of diastereomeric methoxy alcohols was isolated when the IMDAF cycloaddition was carried out in methanol. The major isomer corresponds to the trans-diastereomer that results from trapping of the iminium ion from the less crowded face of the pi-bond. PMID:11674531

  11. Facile Synthesis of Naphthoquinone Spiroketals by Diastereoselective Oxidative [3 + 2] Cycloaddition

    PubMed Central

    Wu, Kun-Liang; Wilkinson, Stephanie; Reich, Norbert O.; Pettus, Thomas R. R.

    2008-01-01

    A highly selective oxidative [3 + 2] cycloaddition of chiral enol ethers and hydroxynaphthoquinone is described. This convergent strategy is amenable to an enantioselective synthesis of β-rubromycin and related naphthoquinone spiroketals. Several compounds were found to inhibit DNA-polymerase and telomerase in a manner resembling α-rubromycin and β-rubromycin. PMID:18044909

  12. Rhodium-Catalyzed Regio- and Stereoselective [2 + 2] Cycloaddition of Allenamides.

    PubMed

    Zheng, Wei-Feng; Bora, Pranjal Protim; Sun, Gui-Jun; Kang, Qiang

    2016-08-01

    A highly regio- and stereoselective Rh-catalyzed intermolecular head-to-head [2 + 2] cycloaddition of allenamides was developed. The intermolecular cycloadducts, trans-dimethylenecyclobutane-1,2-diamine derivatives, were achieved in good yields with high regioselectivity and stereoselectivity. PMID:27403894

  13. Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions.

    PubMed

    Yamashita, Yasuhiro; Yoshimoto, Susumu; Dutton, Mark J; Kobayashi, Shū

    2016-01-01

    Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID:27559396

  14. Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

    PubMed Central

    Yamashita, Yasuhiro; Yoshimoto, Susumu; Dutton, Mark J

    2016-01-01

    Summary Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID:27559396

  15. Extensions of a Basic Laboratory Experiment: [4+2] and [2+2] Cycloadditions

    ERIC Educational Resources Information Center

    Amarne, Hazem Y.; Bain, Alex D.; Neumann, Karen; Zelisko, Paul M.

    2008-01-01

    We describe an extended third-year undergraduate chemistry laboratory exercise in which a number of techniques and concepts are applied to the same set of chemical reactions. The reactions are the photochemical and thermal cycloadditions of [beta]-nitrostyrene and 2,3-dimethylbutadiene. This can be viewed as a single long lab or a series of…

  16. Regio- and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines through Azomethine Ylide Cycloaddition Reaction.

    PubMed

    Haddad, Saoussen; Boudriga, Sarra; Porzio, François; Soldera, Armand; Askri, Moheddine; Knorr, Michael; Rousselin, Yoann; Kubicki, Marek M; Golz, Christopher; Strohmann, Carsten

    2015-09-18

    A series of original spiropyrrolizidine derivatives has been prepared by a one-pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione (isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose an unprecedented isomerization of some spiroadducts leading to a new family of spirooxindolepyrrolizidines. Furthermore, these cycloadducts underwent retro-1,3-dipolar cycloaddition yielding unexpected regioisomers. Upon treatment of the dipolarophiles with in situ generated azomethine ylides from l-proline or acenaphthenequinone, formation of spiroadducts and unusual polycyclic fused piperazines through a stepwise [3 + 3] cycloaddition pathway is observed. The stereochemistry of these N-heterocycles has been confirmed by several X-ray diffraction studies. Some of these compounds exhibit extensive hydrogen bonding in the crystalline state. To enlighten the observed regio- and stereoselectivity of the [3 + 2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction is under kinetic control. PMID:26291879

  17. Asymmetric 1,3-Dipolar Cycloaddition Reactions Catalyzed by Heterocycle-Based Metal Complexes

    NASA Astrophysics Data System (ADS)

    Suga, Hiroyuki

    Highly enantioselective 1,3-dipolar cycloaddition reactions of several 1,3-dipoles, such as nitrones, nitrile oxides, nitrile imines, diazoalkanes, azomethine imines and carbonyl ylides, catalyzed by heterocyclic supramolecular type of metal complexes consisting of chiral heterocyclic compounds and metal salts were described in terms of their ability of asymmetric induction and enantioface differentiation. The scope and limitations of each cycloaddition reactions were also briefly described. Of the chiral hererocycle-based ligands, chiral bisoxazoline, 2,6-bis(oxazolinyl)pyridine, and related oxazoline ligands are shown to be quite effective in obtaining high levels of asymmtric induction. The combination of the bisoxazoline ligand derived from (1S,2R)-cis-1-amino-2-indanol and metal salts was especially efficient for asymmetric cycloaddition reactions of a number of 1,3-dipoles, such as nitrones, nitrile oxide, nitrile imines, diazoacetates and azomethine imines. The metals utilized for the heterocycle-based complexes show a crucial role for degree of asymmetric induction depending upon the 1,3-dipole used. High levels of enantioselectivity were achieved in 1,3-dipolar cycloaddition reactions of unstable carbonyl ylides with benzyloxyacetaldehyde derivatives, α-keto esters, 3-(2-alkenoyl)-2-oxazolidinones, and even vinyl ethers, which were catalyzed by Pybox-lanthanoid metal complexes.

  18. Catalytic asymmetric exo-selective [6+3] cycloaddition of iminoesters with fulvenes.

    PubMed

    Potowski, Marco; Antonchick, Andrey P; Waldmann, Herbert

    2013-09-14

    A novel exo-selective [6+3] cycloaddition approach for the highly enantioselective synthesis of polysubstituted piperidines was developed. The developed methodology was applied in a one-pot [6+3]-[4+2] dicycloaddition, allowing the construction of structurally and stereochemically rich polycyclic compounds from simple building blocks. PMID:23884088

  19. Synthesis of (+/-)-3H-epivincamine via a Rh(II)-triggered cyclization/cycloaddition cascade.

    PubMed

    England, Dylan B; Padwa, Albert

    2007-08-16

    A synthesis of (+/-)-3H-epivincamine is reported. Important steps include (1) a Rh(II)-catalyzed intramolecular [3+2]-cycloaddition of an alpha-diazo indolo amide, (2) a reductive ring opening of the cycloadduct, (3) a decarboethoxylation reaction, and (4) a base-induced keto-amide ring contraction. PMID:17658832

  20. [4+2] and [4+3] catalytic cycloadditions of allenes.

    PubMed

    López, Fernando; Mascareñas, José L

    2014-05-01

    This feature review describes the development of catalytic [4+2] and [4+3] cycloadditions of allenes, as efficient and practical methodologies for assembling six and seven-membered cyclic systems. The different methodologies have been classified depending on the type of key reactive intermediate that was proposed in the catalytic cycle. PMID:24643377

  1. Thermal [2 + 2]-Cycloaddition of Ketenes with Chiral Enol Ethers: Route to Densely Substituted Cyclobutanones.

    PubMed

    Rullière, Pauline; Grisel, Julien; Poittevin, Clément; Cividino, Pascale; Carret, Sébastien; Poisson, Jean-François

    2016-06-17

    Access to chiral polysubstituted cyclobutanones by [2 + 2]-cycloaddition of ketenes with chiral acyclic enol ethers is reported. A wide variety of easily accessible di- and monosubstituted ketenes were found to react with a very high degree of stereoselectivity with chiral, Stericol derived, acyclic enol ethers. This combination of simple reagents provides straightforward entry to highly substituted enantioenriched cyclobutanones. PMID:27232587

  2. Insertion of N-Tosylacetimidates/Acetimidamides onto Arynes via [2 + 2] Cycloaddition.

    PubMed

    Kranthikumar, Ramagonolla; Chegondi, Rambabu; Chandrasekhar, Srivari

    2016-03-18

    A novel insertion reaction of N-tosylacetimidates and N-tosylacetimidamides onto arynes via a benzocyclobutene intermediate followed by ring cleavage is developed to afford o-benzylbenzoic acid derivatives in good yields. Interestingly, the use of cyclic 2-sulfonyliminoindolines provided two distinct products such as azepanimines via [2 + 2] cycloaddition and indolamines via protonation based on solvent medium. PMID:26930224

  3. Iridium-Catalyzed Synthesis of Acylpyridines by [2 + 2 + 2] Cycloaddition of Diynes with Acyl Cyanides.

    PubMed

    Hashimoto, Toru; Kato, Kaoru; Yano, Reiko; Natori, Tomoki; Miura, Hiroki; Takeuchi, Ryo

    2016-07-01

    2-Acylpyridines were prepared by iridium-catalyzed [2 + 2 + 2] cycloaddition of α,ω-diynes with acyl cyanides. [Ir(cod)Cl]2/rac-BINAP or F-DPPE is an efficient catalyst for this reaction. The scope and limitations of this reaction have been disclosed. PMID:27275734

  4. Lewis Acid-Promoted [2+2] Cycloadditions of Alkenes with Arylketenes

    PubMed Central

    Rigsbee, E. M.; Zhou, C.; Rasik, C. M.; Sptiz, A. Z.; Nichols, A. J.; Brown, M. K.

    2015-01-01

    A method for the [2+2] cycloaddition of arylketenes and alkenes is presented. The process involves the in situ generation of a ketene in the presence of a Lewis acid. The utility of products is demonstrated towards the synthesis of a common scaffold found in several natural product families. PMID:26419921

  5. Self‐Assembly of Disorazole C1 through a One‐Pot Alkyne Metathesis Homodimerization Strategy†

    PubMed Central

    Ralston, Kevin J.; Ramstadius, H. Clinton; Brewster, Richard C.; Niblock, Helen S.

    2015-01-01

    Abstract Alkyne metathesis is increasingly explored as a reliable method to close macrocyclic rings, but there are no prior examples of an alkyne‐metathesis‐based homodimerization approach to natural products. In this approach to the cytotoxic C2‐symmetric marine‐derived bis(lactone) disorazole C1, a highly convergent, modular strategy is employed featuring cyclization through an ambitious one‐pot alkyne cross‐metathesis/ring‐closing metathesis self‐assembly process. PMID:27346897

  6. Palladium-Catalyzed Synthesis of Alkynes via a Tandem Decarboxylation/Elimination of (E)-Enol Triflates.

    PubMed

    Munteanu, Charissa; Frantz, Doug E

    2016-08-19

    A mild catalytic synthesis of alkynes via a tandem Pd-catalyzed decarboxylation/elimination of enol triflates is described. Key attributes of the method include readily available starting materials, broad functional group tolerance, and the ability to access terminal, internal, and halogenated alkynes. The preliminary scope of the reaction is demonstrated on 25 different examples with yields ranging from 63% to 96%. PMID:27456435

  7. The different roles of a cationic gold(i) complex in catalysing hydroarylation of alkynes and alkenes with a heterocycle.

    PubMed

    Mehrabi, Tahmineh; Ariafard, Alireza

    2016-08-01

    The mechanism of twofold hydroarylation of terminal alkynes with pyrrole catalyzed by a cationic gold(i) complex was investigated using DFT. It was found that while both the hydroarylation reactions proceed via a Friedel-Crafts-type mechanism, the first hydroarylation is directly promoted by gold(i) but the second hydroarylation by a proton released through interaction of the alkene product with gold-bound acidic organic species such as acetic acid and terminal alkynes. PMID:27377712

  8. Rh-catalysed [5 + 1] cycloaddition of allenylcyclopropanes and CO: reaction development and application to the formal synthesis of (-)-galanthamine.

    PubMed

    Liu, Cheng-Hang; Yu, Zhi-Xiang

    2016-07-01

    A Rh-catalysed [5 + 1] cycloaddition of allenylcyclopropanes and CO has been developed to synthesize functionalized 2-methylidene-3,4-cyclohexenones. The scope of this methodology has been investigated, showing that various functional groups can be tolerated. Both di- and tri-substituted allenylcyclopropanes can be applied to this cycloaddition and the [5 + 1] cycloadducts with the E configuration were obtained as the major products. In addition, the present [5 + 1] cycloaddition reaction has been utilized as a key step in the formal synthesis of the natural product (-)-galanthamine. PMID:27253492

  9. Quantum Chemistry Study of Cycloaddition Pathways for the Reaction of o-Benzyne with Fullerenes and Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard; Han, Jie; Langhoff, Stephen R. (Technical Monitor)

    1997-01-01

    Functionalization of fullerenes via the [2+2] cycloaddition reaction with o-benzyne has been demonstrated in the laboratory. In contrast, [2+4) cycloaddition products are formed when benzyne reacts with planar polycyclic aromatic hydrocarbons. Using density functional theory (DFT) calculations with Becke's hybrid functional and small contracted gaussian basis sets, we are able to reproduce these product preferences. The objective of this work is to explore the functionalization of carbon nanotubes. We have studied o-benzyne cycloaddition products with a [14,0] single-walled nanotube. We find both the [2+2] and [2+4] adducts to be stable, with the latter product being somewhat favored.

  10. Non-Precious Metals Catalyze Formal [4 + 2] Cycloaddition Reactions of 1,2-Diazines and Siloxyalkynes under Ambient Conditions

    PubMed Central

    2015-01-01

    Copper(I) and nickel(0) complexes catalyze the formal [4 + 2] cycloaddition reactions of 1,2-diazines and siloxyalkynes, a reaction hitherto best catalyzed by silver salts. These catalysts based on earth abundant metals are not only competent, but the copper catalyst, in particular, promotes cycloadditions of pyrido[2,3-d]pyridazine and pyrido[3,4-d]pyridazine, enabling a new synthesis of quinoline and isoquinoline derivatives, as well as the formal [2 + 2] cycloaddition reaction of cyclohexenone with a siloxyalkyne. PMID:24911346

  11. Cellular consequences of copper complexes used to catalyze bioorthogonal click reactions.

    PubMed

    Kennedy, David C; McKay, Craig S; Legault, Marc C B; Danielson, Dana C; Blake, Jessie A; Pegoraro, Adrian F; Stolow, Albert; Mester, Zoltan; Pezacki, John Paul

    2011-11-01

    Copper toxicity is a critical issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metabolism, and can be rapidly taken up by cells, all of which can affect their ability to function as catalysts for CuAAC in living systems. Herein, we have evaluated the effects of a number of copper complexes that are typically used to catalyze CuAAC reactions on four human cell lines by measuring mitochondrial activity based on the metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti-Stokes Raman scattering (CARS) microscopy to study effects on lipid metabolism. We find that ligand environment around copper influences all three parameters. Interestingly, for the Cu(II)-bis-L-histidine complex (Cu(his)(2)), cellular uptake and metabolic changes are observed with no toxicity after 72 h at micromolar concentrations. Furthermore, we show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L-histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac(4)ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)(2) or derivatives thereof have potential for in vivo applications where toxicity as well as catalytic activity are critical factors for successful bioconjugation reactions. PMID:21970470

  12. Regioselective C-H Hydroarylation of Internal Alkynes with Arenecarboxylates: Carboxylates as Deciduous Directing Groups.

    PubMed

    Huang, Liangbin; Biafora, Agostino; Zhang, Guodong; Bragoni, Valentina; Gooßen, Lukas J

    2016-06-01

    In the presence of catalytic [Ru(p-cym)I2 ]2 and the base guanidine carbonate, benzoic acids react with internal alkynes to give the corresponding 2-vinylbenzoic acids. This alkyne hydroarylation is generally applicable to diversely substituted electron-rich and electron-poor benzoic and acrylic acids. Aryl(alkyl)acetylenes react regioselectively with formation of the alkyl-branched hydroarylation products, and propargylic alcohols are converted into γ-alkylidene-δ-lactones. The hydroarylation can also be conducted decarboxylatively with a different choice of catalyst and reaction conditions. This reaction variant, which does not proceed via intermediate formation of 2-vinylbenzoic acids, opens up a regioselective, waste-minimized synthetic entry to vinylarenes. PMID:27112925

  13. Dimer Involvement and Origin of Crossover in Nickel-Catalyzed Aldehyde–Alkyne Reductive Couplings

    PubMed Central

    2015-01-01

    The mechanism of nickel(0)-catalyzed reductive coupling of aldehydes and alkynes has been studied. Extensive double-labeling crossover studies have been conducted. While previous studies illustrated that phosphine- and N-heterocyclic carbene-derived catalysts exhibited differing behavior, the origin of these effects has now been evaluated in detail. Many variables, including ligand class, sterics of the ligand and alkyne, temperature, and ring size being formed in intramolecular versions, all influence the extent of crossover observed. A computational evaluation of these effects suggests that dimerization of a key metallacyclic intermediate provides the origin of crossover. Protocols that proceed with crossover are typically less efficient than those without crossover given the thermodynamic stability and low reactivity of the dimeric metallacycles involved in crossover pathways. PMID:25401337

  14. Further studies on hydration of alkynes by the PtCl4-CO catalyst

    SciTech Connect

    Israelsohn, Osnat; Vollhardt, K. Peter C.; Blum, Jochanan

    2002-01-18

    Under CO atmosphere, between 80 and 120 C, a glyme solution of PtCl{sub 4} forms a carbonyl compound that promotes hydration of internal as well as terminal alkynes to give aldehyde-free ketones. The catalytic process depends strongly on the electronic and steric nature of the substrates. Part of the carbonyl functions of the catalyst can be replaced by phosphine ligands. Chiral DIOP reacts with the PtCl{sub 4}-CO compound to give a catalyst that promotes partial kinetic resolution of a racemic alkyne. Replacement of part of the CO by polystyrene-bound diphenylphosphine enables to attach the catalyst to the polymeric support. Upon entrapment of the platinum compound in a silica sol-gel matrix, it reacts as a partially recyclable catalyst. A reformulated mechanism for the PdCl{sub 4}-CO catalyzed hydration is suggested on the basis of the present study.

  15. Validating the alkene and alkyne hydrophosphonylation as an entry to organophosphonates.

    PubMed

    Dondoni, Alessandro; Marra, Alberto

    2015-02-28

    The first paper on the hydrophosphonylation of terminal alkenes was published in 1958 by Stiles and coworkers. Afterwards various papers described organometal-catalyzed and free-radical reactions leading to linear anti-Markovnikov adducts and/or branched Markovnikov products. In 1996 Han and Tanaka reported the first example of alkyne hydrophosphonylation catalyzed by a palladium complex. Further studies using other metal catalysts registered poor selectivity as mixtures of adducts were obtained in most of the cases examined. The first example of alkyne hydrophosphonylation by H-phosphonates under free-radical conditions leading to Z- and E-vinylphosphonates in a 1 : 1 ratio was reported by our group. Nevertheless, Z- to E-isomerization took place upon irradiation in the presence of a thiol. PMID:25609561

  16. Lattice-Directed Formation of Covalent and Organometallic Molecular Wires by Terminal Alkynes on Ag Surfaces.

    PubMed

    Liu, Jing; Chen, Qiwei; Xiao, Lianghong; Shang, Jian; Zhou, Xiong; Zhang, Yajie; Wang, Yongfeng; Shao, Xiang; Li, Jianlong; Chen, Wei; Xu, Guo Qin; Tang, Hao; Zhao, Dahui; Wu, Kai

    2015-06-23

    Surface reactions of 2,5-diethynyl-1,4-bis(phenylethynyl)benzene on Ag(111), Ag(110), and Ag(100) were systematically explored and scrutinized by scanning tunneling microscopy, molecular mechanics simulations, and density functional theory calculations. On Ag(111), Glaser coupling reaction became dominant, yielding one-dimensional molecular wires formed by covalent bonds. On Ag(110) and Ag(100), however, the terminal alkynes reacted with surface metal atoms, leading to one-dimensional organometallic nanostructures. Detailed experimental and theoretical analyses revealed that such a lattice dependence of the terminal alkyne reaction at surfaces originated from the matching degree between the periodicities of the produced molecular wires and the substrate lattice structures. PMID:25990647

  17. Tunable Cascade Reactions of Alkynols with Alkynes under Combined Sc(OTf)3 and Rhodium Catalysis.

    PubMed

    Li, Deng Yuan; Chen, Hao Jie; Liu, Pei Nian

    2016-01-01

    Two tunable cascade reactions of alkynols and alkynes have been developed by combining Sc(OTf)3 and rhodium catalysis. In the absence of H2O, an endo-cycloisomerization/C-H activation cascade reaction provided 2,3-dihydronaphtho[1,2-b]furans in good to high yields. In the presence of H2O, the product of alkynol hydration underwent an addition/C-H activation cascade reaction with an alkyne, which led to the formation of 4,5-dihydro-3H-spiro[furan-2,1'-isochromene] derivatives in good yields under mild reaction conditions. Mechanistic studies of the cascade reactions indicated that the rate-determining step involves C-H bond cleavage and that the hydration of the alkynol plays a key role in switching between the two reaction pathways. PMID:26531133

  18. C-84 Selective Porphyrin Macrocycle with an Adaptable Cavity Constructed Through Alkyne Metathesis

    SciTech Connect

    Zhang, C. X.; Long, H.; Zhang, W.

    2012-06-21

    A bisporphyrin macrocycle was constructed from a porphyrin-based diyne monomer in one step through alkyne metathesis. The fullerene binding studies (C{sub 60}, C{sub 70} and C{sub 84}) showed the highest binding affinity of the macrocycle for C{sub 84}, which is in great contrast to its bisporphyrin four-armed cage analogue that showed the strongest binding with C{sub 70}.

  19. Synthesis of 2-Alkynoates by Palladium(II)-Catalyzed Oxidative Carbonylation of Terminal Alkynes and Alcohols.

    PubMed

    Cao, Qun; Hughes, N Louise; Muldoon, Mark J

    2016-08-16

    A homogeneous Pd(II) catalyst, utilizing a simple and inexpensive amine ligand (TMEDA), allows 2-alkynoates to be prepared in high yields by an oxidative carbonylation of terminal alkynes and alcohols. The catalyst system overcomes many of the limitations of previous palladium carbonylation catalysts. It has an increased substrate scope, avoids large excesses of alcohol substrate and uses a desirable solvent. The catalyst employs oxygen as the terminal oxidant and can be operated under safer gas mixtures. PMID:27305489

  20. Copper-catalyzed 1,2-addition of α-carbonyl iodides to alkynes.

    PubMed

    Xu, Tao; Hu, Xile

    2015-01-19

    β,γ-Unsaturated ketones are an important class of organic molecules. Herein, copper catalysis has been developed for the synthesis of β-γ-unsaturated ketones through 1,2-addition of α-carbonyl iodides to alkynes. The reactions exhibit wide substrate scope and high functional group tolerance. The reaction products are versatile synthetic intermediates to complex small molecules. The method was applied for the formal synthesis of (±)-trichostatin A, a histone deacetylase inhibitor. PMID:25470461

  1. Cyclization of Alkyne-Azide with Isonitrile/CO via Self-Relay Rhodium Catalysis.

    PubMed

    Zhang, Zhen; Xiao, Fan; Huang, Baoliang; Hu, Jincheng; Fu, Bin; Zhang, Zhenhua

    2016-03-01

    A self-relay rhodium(I)-catalyzed cyclization of alkyne-azides with two σ-donor/π-acceptor ligands (isonitriles and CO) to form sequentially multiple-fused heterocycle systems via tandem nitrene transformation and aza-Pauson-Khand cyclization has been developed. In this approach, an intriguing chemoselective insertion process of isonitriles superior to CO was observed. This reaction provides an alternative strategy to synthesize functionalized pyrrolo[2,3-b]indole scaffolds. PMID:26907671

  2. Copper mediated stereoselective synthesis of C-glycosides from unactivated alkynes.

    PubMed

    Kusunuru, Anil Kumar; Tatina, Madhubabu; Yousuf, Syed Khalid; Mukherjee, Debaraj

    2013-10-01

    A highly stereoselective rapid C-glycosylation reaction has been developed between glycal and unactivated alkynes in the presence of coppertriflate and ascorbic acid at low catalyst loading and at room temperature. A wide variety of glycals and aryl acetylenes participate in the reaction smoothly. TfOH generated during the reduction of Cu(OTf)2 by ascorbic acid may be the active catalyst for the glycosylation. PMID:24049771

  3. Disorder-to-order transition of diblock copolymers induced by alkyne/azide click chemistry

    NASA Astrophysics Data System (ADS)

    Wei, Xinyu; Chen, Wei; Chen, Xiangji; Emrick, Todd; Russell, Thomas

    2010-03-01

    Alkyne/azide click chemistry is shown as a novel approach to induce the disorder-to-order transition (DOT) of diblock copolymers. A series of poly(ethylene oxide)-b-poly(n-butyl methacrylate-r-propargyl methacrylate) (PEO-b-P(nBMA-r-PgMA)) diblock copolymers were prepared and it is shown that the neat diblock copolymers are in the phase mixed state over the temperature range invetigated. Microphase separation was observed when the diblock copolymers were mixed with rhodamine B azide and annealed at elevated temperature. The azide molecule reacted with the terminal alkyne groups in P(nBMA-r-PgMA) block and attached to polymer backbone, resulting in a significant increase in the nonfavorable interaction between the two blocks. The DOT of these blends was observed both in the bulk and in thin films. The evolution of the morphology during the transition is determined by the mole ratio between alkyne and azide groups, annealing time and temperature, and interfacial energy.

  4. Development of Alkyne-Containing Pyrazolopyrimidines To Overcome Drug Resistance of Bcr-Abl Kinase.

    PubMed

    Liu, Xu; Kung, Alvin; Malinoski, Brock; Prakash, G K Surya; Zhang, Chao

    2015-12-10

    Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-Abl(T315I) by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only Abl(T315I) in vitro but also Bcr-Abl(T315I) in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML. PMID:26562217

  5. Ru Catalyzed Alkene-Alkyne Coupling. Total Synthesis of Amphidinolide P

    PubMed Central

    Trost, Barry M.; Papillon, Julien P. N.; Nussbaumer, Thomas

    2008-01-01

    A coordinatively unsaturated ruthenium complex catalyzed the formation of a carbon-carbon bond between two judiciously chosen alkene and alkyne partners in good yield, and in a chemo- and regioselective fashion, in spite of the significant degree of unsaturation of the substrates. The resulting 1,4-diene forms the backbone of the cytotoxic marine natural product amphidinolide P. The alkene partner was rapidly assembled from (R)-glycidyl tosylate, which served as a linchpin in a one-flask, sequential three-components coupling process using vinyllithium and a vinyl cyanocuprate. The synthesis of the alkyne partner made use of an unusual anti-selective addition under chelation control conditions of an allyltin reagent derived from tiglic acid. In addition, a remarkably E-selective E2 process using the azodicarboxylate-triphenylphosphine system is featured. Also featured is the first example of the use of a β-lactone as a thermodynamic spring to effect macrolactonization. The oxetanone ring was thus used as a productive protecting group that increased the overall efficiency of this total synthesis. This work was also an opportunity to further probe the scope of the ruthenium-catalyzed alkene-alkyne coupling, in particular using enynes, and studies using various functionalized substrates are described. PMID:16351124

  6. The Role of Ate Complexes in the Copper-Mediated Trifluoromethylation of Alkynes.

    PubMed

    Weske, Sebastian; Schoop, Ramona; Koszinowski, Konrad

    2016-08-01

    Trifluoromethylation reactions have recently received increased attention because of the beneficial effect of the trifluoromethyl group on the pharmacological properties of numerous substances. A common method to introduce the trifluoromethyl group employs the Ruppert-Prakash reagent, that is, Si(CH3 )3 CF3 , together with a copper(I) halide. We have applied this method to the trifluoromethylation of aromatic alkynes and used electrospray-ionization mass spectrometry to investigate the mechanism of these reactions in tetrahydrofuran, dichloromethane, and acetonitrile as well as with and without added 1,10-phenanthroline. In the absence of the alkyne component, the homoleptic ate complexes [Cu(CF3 )2 ](-) and [Cu(CF3 )4 ](-) were observed. In the presence of the alkynes RH, the heteroleptic complexes [Cu(CF3 )3 R](-) were detected as well. Upon gas-phase fragmentation, these key intermediates released the cross-coupling products R-CF3 with perfect selectivity. Apparently, the [Cu(CF3 )3 R](-) complexes did not originate from homoleptic cuprate anions, but from unobservable neutral precursors. The present results moreover point to the involvement of oxygen as the oxidizing agent. PMID:27385188

  7. A novel alkyne cholesterol to trace cellular cholesterol metabolism and localization.

    PubMed

    Hofmann, Kristina; Thiele, Christoph; Schött, Hans-Frieder; Gaebler, Anne; Schoene, Mario; Kiver, Yuriy; Friedrichs, Silvia; Lütjohann, Dieter; Kuerschner, Lars

    2014-03-01

    Cholesterol is an important lipid of mammalian cells and plays a fundamental role in many biological processes. Its concentration in the various cellular membranes differs and is tightly regulated. Here, we present a novel alkyne cholesterol analog suitable for tracing both cholesterol metabolism and localization. This probe can be detected by click chemistry employing various reporter azides. Alkyne cholesterol is accepted by cellular enzymes from different biological species (Brevibacterium, yeast, rat, human) and these enzymes include cholesterol oxidases, hydroxylases, and acyl transferases that generate the expected metabolites in in vitro and in vivo assays. Using fluorescence microscopy, we studied the distribution of cholesterol at subcellular resolution, detecting the lipid in the Golgi and at the plasma membrane, but also in the endoplasmic reticulum and mitochondria. In summary, alkyne cholesterol represents a versatile, sensitive, and easy-to-use tool for tracking cellular cholesterol metabolism and localization as it allows for manifold detection methods including mass spectrometry, thin-layer chromatography/fluorography, and fluorescence microscopy. PMID:24334219

  8. Evaluation of alkyne-modified isoprenoids as chemical reporters of protein prenylation

    PubMed Central

    DeGraw, Amanda J.; Palsuledesai, Charuta; Ochocki, Joshua D.; Dozier, Jonathan K.; Lenevich, Stepan; Rashidian, Mohammad; Distefano, Mark D.

    2010-01-01

    Protein prenyltransferases catalyze the attachment of C15 (farnesyl) and C20 (geranylgeranyl) groups to proteins at specific sequences localized at or near the C-termini of specific proteins. Determination of the specific protein prenyltransferase substrates affected by the inhibition of these enzymes is critical for enhancing knowledge of the mechanism of such potential drugs. Here we investigate the utility of alkyne-containing isoprenoid analogues for chemical proteomics experiments by showing that these compounds readily penetrate mammalian cells in culture and become incorporated into proteins that are normally prenylated. Derivatization via Cu(I) catalyzed Click reaction with a fluorescent azide reagent allows the proteins to be visualized and their relative levels to be analyzed. Simultaneous treatment of cells with these probes and inhibitors of prenylation reveals decreases in the levels of some but not all of the labeled proteins. Two-dimensional electrophoretic separation of these labeled proteins followed by mass spectrometric analysis allowed several labeled proteins to be unambiguously identified. Docking experiments and DFT calculations suggest that the substrate specificity of PFTase may vary depending on whether azide- or alkyne-based isoprenoid analogues are employed. These results demonstrate the utility of alkyne-containing analogues for chemical proteomic applications. PMID:21040496

  9. 'Click' chemistry synthesis and capillary electrophoresis study of 1,4-linked 1,2,3-triazole AZT-systemin conjugate.

    PubMed

    Dobkowski, Michał; Szychowska, Aleksandra; Pieszko, Małgorzata; Miszka, Anna; Wojciechowska, Monika; Alenowicz, Magdalena; Ruczyński, Jarosław; Rekowski, Piotr; Celewicz, Lech; Barciszewski, Jan; Mucha, Piotr

    2014-09-01

    The Cu(I) catalyzed Huisgen 1,3-dipolar azide-alkyne cycloaddition (CuAAC) was applied for a nucleoside-peptide bioconjugation. Systemin (Sys), an 18-aa plant signaling peptide naturally produced in response to wounding or pathogen attack, was chemically synthesized as its N-propynoic acid functionalized analog (Prp-Sys) using the SPPS. Next, CuAAC was applied to conjugate Prp-Sys with 3'-azido-2',3'-dideoxythymidine (AZT), a model cargo molecule. 1,4-Linked 1,2,3-triazole AZT-Sys conjugate was designed to characterize the spreading properties and ability to translocate of cargo molecules of systemin. CuAAC allowed the synthesis of the conjugate in a chemoselective and regioselective manner, with high purity and yield. The presence of Cu(I) ions generated in situ drove the CuAAC reaction to completion within a few minutes without any by-products. Under typical separation conditions of phosphate 'buffer' at low pH and uncoated fused bare-silica capillary, an increasing peak intensity assigned to triazole-linked AZT-Sys conjugate was observed using capillary electrophoresis (CE) during CuAAC. CE analysis showed that systemin peptides are stable in tomato leaf extract for up to a few hours. CE-ESI-MS revealed that the native Sys and its conjugate with AZT are translocated through the tomato stem and can be directly detected in stem exudates. The results show potential application of systemin as a transporter of low molecular weight cargo molecules in tomato plant and of CE method to characterize a behavior of plant peptides and its analogs. PMID:24889517

  10. Cross-Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3+2]-Cyclization of 1,4-Diazabutatriene.

    PubMed

    Hu, Zhongyan; Yuan, Haiyan; Men, Yang; Liu, Qun; Zhang, Jingping; Xu, Xianxiu

    2016-06-13

    A new cross-cycloaddition reaction between a wide range of isocyanides and 2-isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo[3,4-b]indoles under thermal conditions. On the basis of the experimental results and DFT calculations, a mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates, followed by an intramolecular [3+2]-cycloaddition and 1,3-proton shift. PMID:27135199

  11. Cascade Reaction of Donor-Acceptor Cyclopropanes: Mechanistic Studies on Cycloadditions with Nitrosoarenes and cis-Diazenes.

    PubMed

    Chidley, Tristan; Vemula, Naresh; Carson, Cheryl A; Kerr, Michael A; Pagenkopf, Brian L

    2016-06-17

    Tandem ring opening, elimination, and cycloaddition of donor-acceptor cyclopropanes were observed in Yb(OTf)3-catalyzed cycloaddition with nitrosoarenes. The reaction results in formation of tetrahydro-1,2-oxazine instead of the normal cycloadduct isoxazolidine via in situ nitrone formation. A similar cascade sequence was observed with cis-diazines. Mechanistic studies on this unique transformation offer an entirely new approach for reaction design with donor-acceptor cyclopropanes. PMID:27267360

  12. Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A.

    PubMed

    Patel, Ashay; Chen, Zhuo; Yang, Zhongyue; Gutiérrez, Osvaldo; Liu, Hung-Wen; Houk, K N; Singleton, Daniel A

    2016-03-23

    SpnF, an enzyme involved in the biosynthesis of spinosyn A, catalyzes a transannular Diels-Alder reaction. Quantum mechanical computations and dynamic simulations now show that this cycloaddition is not well described as either a concerted or stepwise process, and dynamical effects influence the identity and timing of bond formation. The transition state for the reaction is ambimodal and leads directly to both the observed Diels-Alder and an unobserved [6+4] cycloadduct. The potential energy surface bifurcates and the cycloadditions occur by dynamically stepwise modes featuring an "entropic intermediate". A rapid Cope rearrangement converts the [6+4] adduct into the observed [4+2] adduct. Control of nonstatistical dynamical effects may serve as another way by which enzymes control reactions. PMID:26909570

  13. Menthols as Chiral Auxiliaries for Asymmetric Cycloadditive Oligomerization: Syntheses and Studies of β-Proline Hexamers.

    PubMed

    Kudryavtsev, Konstantin V; Ivantcova, Polina M; Muhle-Goll, Claudia; Churakov, Andrei V; Sokolov, Mikhail N; Dyuba, Artem V; Arutyunyan, Alexander M; Howard, Judith A K; Yu, Chia-Chun; Guh, Jih-Hwa; Zefirov, Nikolay S; Bräse, Stefan

    2015-12-18

    To produce a novel class of structurally ordered poly-β-prolines, an emergent method for synthesizing chiral β-peptide molecular frameworks was developed based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Functionalized short β-peptides with up to six monomeric residues were efficiently synthesized in homochiral forms using a cycloadditive oligomerization approach. X-ray, NMR, and CD structural analyses of the novel β-peptides revealed secondary structure features that were generated primarily by Z/E-β-peptide bond isomerism. Anticancer in cellulo activity of the new β-peptides toward hormone-refractory prostate cancer cells was observed and was dependent on the absolute configuration of the stereogenic centers and the chain length of the β-proline oligomers. PMID:26624275

  14. An efficient, overall [4+1] cycloaddition of 1,3-dienes and nitrene precursors.

    PubMed

    Wu, Qiong; Hu, Jian; Ren, Xinfeng; Zhou, Jianrong

    2011-10-01

    Intermolecular cycloadditions of conjugated dienes and nitrene precursors usually produce aziridines. A generally useful method was lacking to directly provide the [4+1] cycloadducts, 3-pyrrolines. We have realized this transformation by using an uniquely active catalyst, copper(II) 1,1,1,5,5,5-hexafluoroacetylacetonate ([Cu(hfacac)(2)]). The method is applicable to a wide array of dienes with good yields. When 1,4-disubstituted dienes are used as substrates, good-to-excellent cis or trans selectivity can be obtained. Interestingly, the cis or trans preference depends on the nature of the substituents, rather than diene geometry. Mechanistic studies reveal that the [4+1] cycloaddition proceeds through diene aziridination and subsequent ring expansion. Among common copper catalysts, only [Cu(hfacac)(2)] can efficiently catalyze both steps, which explains the unique efficiency of the catalyst. PMID:21887836

  15. Theoretical study on cycloaddition of singlet dichlorocarbene with formaldehyde, acetaldehyde and benzaldehyde and subsequent rearrangement reactions

    NASA Astrophysics Data System (ADS)

    Peng, L.; Li, Q. S.; Fang, W. H.; Fu, C. J.; Zhang, J.

    2003-11-01

    Cycloaddition reactions of the singlet CCl 2 carbene with H 2CO, CH 3CHO and C 6H 5CHO and the subsequent rearrangement processes have been investigated with density functional theory. It was found that the interaction between the σ orbital of CCl 2 and the CO π* orbital plays an important role in the cycloaddition reactions. The addition reaction of CCl 2 with H 2CO proceeds very easily, which is slightly influenced by the methyl and phenyl substitutions. However, the substitutions significantly reduce the barrier to the rearrangement reactions. The interaction between solvent and solute has a little influence on the structures of the stationary points, but has a noticeable influence on the barrier heights of the rearrangement reactions.

  16. Mechanism and Dynamic Correlation Effects in Cycloaddition Reactions of Singlet Difluorocarbene to Alkenes and Disilene

    NASA Astrophysics Data System (ADS)

    Gao, Xingfa; Ohtsuka, Yuhki; Ishimura, Kazuya; Nagase, Shigeru

    2009-08-01

    Mechanisms of the cycloaddition reactions of singlet difluorocarbene (CF2) to alkenes and disilene were studied using CASSCF, MR-MP2, CR-CC(2,3), and UB3LYP methods in combination with basis sets up to 6-311++G(3d,p). The CASSCF(4,4) energies suggest that the cycloadditions all follow the stepwise mechanism. However, energies calculated using the MR-MP2(4,4) and CR-CC(2,3) methods in combination with the 6-311G(d) or larger basis sets consistently show that the reactions follow a concerted mechanism. The stepwise mechanisms predicted at the CASSCF level are "artificial" because of their neglect of dynamic electron correlation effects. The importance of dynamic electron correlation in determining the mechanistic nature of the reactions is explained through knowledge of the reacting system's geometries and charges along the reaction path.

  17. Trimethylenemethane diyl mediated tandem cycloaddition reactions: mechanism based design of synthetic strategies.

    PubMed

    Lee, Hee-Yoon

    2015-08-18

    Several criteria for the measure of synthetic strategies toward "ideal synthesis" are available to guide the design and evaluation of the synthetic strategies toward the target molecules. One strategy toward "ideal synthesis" is developing a multistep reaction that involves dramatic change in complexity. Biogenesis of natural products and mechanistic investigation of complicated organic transformation provide good inspiration for design of new synthetic strategies. Trimethylenemethane diradical (TMM diyl), first introduced only as a theoretically interesting structure 60 years ago, gained interests of physical organic chemistry when it was first detected by Dowd. Study of characteristics and properties of TMM diyl was accelerated in a great deal when Koebrich observed dimeric hydrocarbon products from the reaction of 1,1-dibromo-2-methylhexa-1,5-diene with MeLi. Berson followed the mechanistic investigation of the reaction that involved 2-methylenecyclopentane-1,3-diyl, and thoroughly studied physical and chemical properties of the TMM diyl. This lead to the development of intramolecular [2 + 3] TMM diyl cycloaddition reaction for the construction of linearly fused triquinanes by Little. We envisioned that the generation of a TMM diyl through cycloaddition reaction discovered by Koebrich and [2 + 3] cycloaddition reaction of the TMM diyl could be combined together to form polyquinane structures. A cycloaddition reaction sequence of generating a TMM diyl from a alkylidene carbene of 2-methylhexa-1,5-diene structure in the presence of another olefin was designed and executed to produce linearly fused and angularly fused triquinanes depending on the connectivity of the second double bond. The successful transformation also inspired design of a tandem cycloaddition reaction strategy of using unprecedented tetrahydrocyclopentapyrazole to TMM diyl transformation. The new design involves two [2 + 3] cycloaddition reactions of 6-diazohexa-1,2-diene with an olefin attached

  18. Rhodium(II)-Catalyzed Cycloaddition Reactions of Non-classical 1,5-Dipoles for the Formation of Eight-Membered Heterocycles.

    PubMed

    Lee, Dong Jin; Ko, Donguk; Yoo, Eun Jeong

    2015-11-01

    A new type of intermolecular rhodium(II)-catalyzed [5+3] cycloaddition has been developed. This higher-order cycloaddition between pyridinium zwitterion 1,5-dipole equivalents and enol diazoacetates enables the formation of eight-membered heterocyclic skeletons, which are otherwise difficult to construct. The optimized cycloaddition occurs efficiently under mild conditions with a wide range of pyridinium zwitterions and with high functional-group tolerance. PMID:26376924

  19. Metal-free intermolecular formal cycloadditions enable an orthogonal access to nitrogen heterocycles

    PubMed Central

    Xie, Lan-Gui; Niyomchon, Supaporn; Mota, Antonio J.; González, Leticia; Maulide, Nuno

    2016-01-01

    Nitrogen-containing heteroaromatic cores are ubiquitous building blocks in organic chemistry. Herein, we present a family of metal-free intermolecular formal cycloaddition reactions that enable highly selective and orthogonal access to isoquinolines and pyrimidines at will. Applications of the products are complemented by a density functional theory mechanistic analysis that pinpoints the crucial factors responsible for the selectivity observed, including stoichiometry and the nature of the heteroalkyne. PMID:26975182

  20. Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl Enol Ethers.

    PubMed

    Yang, Bo; Lu, Zhan

    2016-08-19

    Visible-light-promoted oxidative [4 + 2] cycloadditions of ε,3-unsaturated silyl enol ethers have been developed to efficiently and diastereoselectively construct polycyclic skeletons under mild conditions. The diastereoselectivities were dependent on the stereoconfiguration of silyl enol ether, substitutions on the link, as well as electric properties of substitutions on aryl rings. The intermediates could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron oxidation of the silyl enol ether. PMID:27391768

  1. Catalyst free visible light induced cycloaddition as an avenue for polymer ligation.

    PubMed

    Lederhose, Paul; Wüst, Kilian N R; Barner-Kowollik, Christopher; Blinco, James P

    2016-05-21

    The current study introduces a tetrazole species able to perform a rapid, visible light induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC). Full conversion of the tetrazole species under mild, catalyst free conditions is reported. Importantly, the visible light ligation technology is applied as a method for the modification and ligation of polymers featuring the rapid, clean and exclusive formation of the desired cycloadduct. PMID:27004740

  2. Highly diastereoselective and enantioselective formal [4 + 3] cycloaddition of donor-acceptor cyclobutanes with nitrones.

    PubMed

    Hu, Jiang-Lin; Wang, Lijia; Xu, Hao; Xie, Zuowei; Tang, Yong

    2015-06-01

    The first highly diastereoselective and enantioselective catalytic formal [4 + 3] cycloaddition of 1,1-cyclobutane diester with nitrone has been developed. Sterically hindered chiral SaBOX/Cu(II) complex promotes the reaction efficiently with a broad substrate scope, producing a range of multifunctionalized optically active 1,2-oxazepanes with excellent stereocontrol (up to >99/1 dr and 97% ee). PMID:25974724

  3. Photocatalytic synthesis of dihydrobenzofurans by oxidative [3+2] cycloaddition of phenols.

    PubMed

    Blum, Travis R; Zhu, Ye; Nordeen, Sarah A; Yoon, Tehshik P

    2014-10-01

    We report a protocol for oxidative [3+2] cycloadditions of phenols and alkenes applicable to the modular synthesis of a large family of dihydrobenzofuran natural products. Visible-light-activated transition metal photocatalysis enables the use of ammonium persulfate as an easily handled, benign terminal oxidant. The broad range of organic substrates that are readily oxidized by photoredox catalysis suggests that this strategy may be applicable to a variety of useful oxidative transformations. PMID:25155300

  4. Synthesis of 2H-Indazoles by the [3 + 2] Dipolar Cycloaddition of Sydnones with Arynes

    PubMed Central

    Fang, Yuesi; Wu, Chunrui; Larock, Richard C.; Shi, Feng

    2011-01-01

    A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles. PMID:21970468

  5. Chiral Phosphoric Acid-Catalyzed Enantioselective Formal [3+2] Cycloaddition of Azomethine Imines with Enecarbamates.

    PubMed

    Wang, Yang; Wang, Qian; Zhu, Jieping

    2016-06-01

    The first catalytic asymmetric inverse electron demand 1,3-dipolar cycloaddition of azomethine imines with enecarbamates has been developed. Isoquinoline-fused pyrazolidines containing two or three contiguous stereogenic centers were obtained in high yields with excellent regio-, diastereo-, and enantioselectivities. The pyrazolidine ring can be opened to install an aminal, α-amino nitrile, or homoallylamine function with an excellent control of the newly generated stereogenic center. Access to aminobenzo[a]quinolizidine is also documented. PMID:27135440

  6. Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

    PubMed Central

    Yamada, Mizuki; Matsumura, Mio; Uchida, Yuki; Kawahata, Masatoshi; Murata, Yuki; Kakusawa, Naoki; Yamaguchi, Kentaro

    2016-01-01

    Summary Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. PMID:27559379

  7. Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition.

    PubMed

    Xu, Hao; Golz, Christopher; Strohmann, Carsten; Antonchick, Andrey P; Waldmann, Herbert

    2016-06-27

    An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst. PMID:27193834

  8. Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides.

    PubMed

    Yamada, Mizuki; Matsumura, Mio; Uchida, Yuki; Kawahata, Masatoshi; Murata, Yuki; Kakusawa, Naoki; Yamaguchi, Kentaro; Yasuike, Shuji

    2016-01-01

    Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. PMID:27559379

  9. Stereocontrolled cyclic nitrone cycloaddition strategy for the synthesis of pyrrolizidine and indolizidine alkaloids.

    PubMed

    Brandi, Alberto; Cardona, Francesca; Cicchi, Stefano; Cordero, Franca M; Goti, Andrea

    2009-08-10

    The synthesis of polyhydroxylated indolizidines and pyrrolizidines belonging to the class of iminosugars, endowed with a vast and assorted biological activity, can be achieved in a straightforward manner by a general strategy consisting of a highly stereoselective 1,3-dipolar cycloaddition of polyhydroxylated pyrroline-N-oxides followed by simple transformations of the isoxazolidine adducts. The strategy allows the complete control of the relative and absolute stereochemistry of the numerous stereogenic centers decorating these compounds. PMID:19585642

  10. Gold carbenes, gold-stabilized carbocations, and cationic intermediates relevant to gold-catalysed enyne cycloaddition.

    PubMed

    Harris, R J; Widenhoefer, R A

    2016-08-21

    Cationic gold complexes in which gold is bound to a formally divalent carbon atom, typically formulated as gold carbenes or α-metallocarbenium ions, have been widely invoked in a range of gold-catalyzed transformations, most notably in the gold-catalyzed cycloisomerization of 1,n-enynes. Although the existence of gold carbene complexes as intermediates in gold-catalyzed transformations is supported by a wealth of indirect experimental data and by computation, until recently no examples of cationic gold carbenes/α-metallocarbenium ions had been synthesized nor had any cationic intermediates generated via gold-catalyzed enyne cycloaddition been directly observed. Largely for this reason, there has been considerable debate regarding the electronic structure of these cationic complexes, in particular the relative contributions of the carbene (LAu(+)[double bond, length as m-dash]CR2) and α-metallocarbenium (LAu-CR2(+)) forms, which is intimately related to the extent of d → p backbonding from gold to the C1 carbon atom. However, over the past ∼ seven years, a number of cationic gold carbene complexes have been synthesized in solution and generated in the gas phase and cationic intermediates have been directly observed in the gold-catalyzed cycloaddition of enynes. Together, these advances provide insight into the nature and electronic structure of gold carbene/α-metallocarbenium complexes and the cationic intermediates generated via gold-catalyzed enyne cycloaddition. Herein we review recent advances in this area. PMID:27146712

  11. New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition

    PubMed Central

    Payne, Karl A.P.; White, Mark D.; Fisher, Karl; Khara, Basile; Bailey, Samuel S.; Parker, David; Rattray, Nicholas J.W.; Trivedi, Drupad K.; Goodacre, Royston; Beveridge, Rebecca; Barran, Perdita; Rigby, Stephen E.J.; Scrutton, Nigel S.; Hay, Sam; Leys, David

    2016-01-01

    The ubiD/ubiX or the homologous fdc/pad genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone biosynthesis1–3 or microbial biodegradation of aromatic compounds4–6 respectively. Despite biochemical studies on individual gene products, the composition and co-factor requirement of the enzyme responsible for in vivo decarboxylase activity remained unclear7–9. We show Fdc is solely responsible for (de)carboxylase activity, and that it requires a new type of cofactor: a prenylated flavin synthesised by the associated UbiX/Pad10. Atomic resolution crystal structures reveal two distinct isomers of the oxidized cofactor can be observed: an isoalloxazine N5-iminium adduct and a N5 secondary ketimine species with drastically altered ring structure, both having azomethine ylide character. Substrate binding positions the dipolarophile enoic acid group directly above the azomethine ylide group. The structure of a covalent inhibitor-cofactor adduct suggests 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. While 1,3-dipolar cycloaddition is commonly used in organic chemistry11–12, we propose this presents the first example of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for Fdc/UbiD catalysis offers new routes in alkene hydrocarbon production or aryl (de)carboxylation. PMID:26083754

  12. Direct visualization of a cycloaddition reaction on frozen asymmetric Si dimers at room temperature

    NASA Astrophysics Data System (ADS)

    Baik, Jaeyoon; Ihm, Kyuwook; Ha, Taekyun; An, Ki-Seok; Ahn, Joung Real; Park, Chong-Yun

    2016-07-01

    We firstly report an experimental visualization of a cycloaddition reaction on RT frozen asymmetric Si dimers. The frozen Si dimers with a local c(4 × 2) order were prepared by pinning flip-flopping Si dimers by using molecules. This RT pristine c(4 × 2) structure was used to determine what Si atom of an asymmetric Si dimer bonds to a molecule at the initial stage of the RT cycloaddition reaction, which has been a long-standing puzzling issue. This made it possible to compare directly experimental cycloaddition reactions with theoretical ones. As a prototype for the experiment, a 1,3-butadiene molecule adsorbed between Si dimer rows was used. The 1,3-butadiene molecule was found to prefer a symmetric Si pair on the frozen Si dimers, i.e., two electrophilic lower atoms of asymmetric Si dimers. This result is consistent with the theoretical prediction that a 1,3-diene molecule prefers a symmetric Si pair on the Si(001)c(4 × 2) surface. This experimental approach can also be applied to other studies for the adsorption of a molecule on a Si(001) surface at room temperature.

  13. An experimental and computational assessment of acid-catalyzed azide-nitrile cycloadditions.

    PubMed

    Cantillo, David; Gutmann, Bernhard; Kappe, C Oliver

    2012-12-01

    The mechanism of the azide-nitrile cycloaddition mediated by different Brønsted and Lewis acids has been addressed through DFT calculations. In all cases activation of the nitrile substrate by the Brønsted or Lewis acid catalyst was found to be responsible for the rate enhancement. According to DFT calculations the cycloaddition proceeds in a stepwise fashion involving the initial formation of an open-chain imidoyl azide intermediate. Kinetic experiments performed using N-methyl-2-pyrrolidone as solvent and sodium azide as azide source demonstrate that all evaluated Brønsted acids have the same efficiency toward cycloaddition with benzonitrile, suggesting that hydrazoic acid is the actual dominant catalytic species in these tetrazole syntheses. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus. The most efficient catalyst evaluated was 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, which can readily be generated in situ from aluminum chloride, sodium azide in N-methyl-2-pyrrolidone. The efficiency of this catalyst has been examined by preparation of a series of 5-substituted-1H-tetrazoles. The desired tetrazole structures were obtained in high yields within 3-10 min employing controlled microwave heating. PMID:23126486

  14. Enantiodivergent Synthesis of Bis-Spiropyrrolidines via Sequential Interrupted and Completed (3 + 2) Cycloadditions.

    PubMed

    Conde, Egoitz; Rivilla, Iván; Larumbe, Amaia; Cossío, Fernando P

    2015-12-01

    Both (5R)- and (5S)-1,7-diazaspiro[4.4]nonan-6-ones are obtained via a sequence of interrupted and completed stepwise (3 + 2) cycloadditions between azomethine ylides and π-deficient alkenes. The only source of chirality along the whole process is an enantiopure ferrocenyl pyrrolidine catalytic ligand. When the starting imine incorporates two aryl groups or one aryl group with one electron-releasing substituent, the reaction between the azomethine ylide and the alkene stops at the first step, leading to the corresponding Michael adduct. When imines derived from p-methoxybenzaldehyde are used, the corresponding syn-α-amino-γ-nitro ester is obtained with almost complete enantiocontrol. In contrast, imines derived from benzophenone lead to the corresponding anti analogue. From this interrupted (3 + 2) cycloaddition, cis- and trans-α-amino-γ-lactams can be obtained via hydrogenation of the nitro group followed by in situ cyclization. Imines derived from these latter compounds are the precursors of N-metalated azomethine ylides from which up to four new chiral centers can be generated via completed (3 + 2) cycloaddition reactions with full regio- and diastereocontrol. Cis- and trans-γ-lactams lead to opposite bis-spiropyrrolidine enantiomers. Therefore, both enantiomeric series of spiro compounds can be obtained by means of the same catalytic system. The potential of these rigid, densely substituted homochiral compounds in medicinal chemistry is briefly described. PMID:26439974

  15. Theory of the formation and decomposition of N-heterocyclic aminooxycarbenes through metal-assisted [2+3]-dipolar cycloaddition/retro-cycloaddition.

    PubMed

    Novikov, Alexander S; Kuznetsov, Maxim L; Pombeiro, Armando J L

    2013-02-18

    The theoretical background of the formation of N-heterocyclic oxadiazoline carbenes through a metal-assisted [2+3]-dipolar cycloaddition (CA) reaction of nitrones R(1)CH=N(R(2))O to isocyanides C≡NR and the decomposition of these carbenes to imines R(1)CH=NR(2) and isocyanates O=C=NR is discussed. Furthermore, the reaction mechanisms and factors that govern these processes are analyzed in detail. In the absence of a metal, oxadiazoline carbenes should not be accessible due to the high activation energy of their formation and their low thermodynamic stability. The most efficient promotors that could assist the synthesis of these species should be "carbenophilic" metals that form a strong bond with the oxadiazoline heterocycle, but without significant involvement of π-back donation, namely, Au(I), Au(III), Pt(II), Pt(IV), Re(V), and Pd(II) metal centers. These metals, on the one hand, significantly facilitate the coupling of nitrones with isocyanides and, on the other hand, stabilize the derived carbene heterocycles toward decomposition. The energy of the LUMO(CNR) and the charge on the N atom of the C≡N group are principal factors that control the cycloaddition of nitrones to isocyanides. The alkyl-substituted nitrones and isocyanides are predicted to be more active in the CA reaction than the aryl-substituted species, and the N,N,C-alkyloxadiazolines are more stable toward decomposition relative to the aryl derivatives. PMID:23296691

  16. Enantioselective Ruthenium Catalyzed Carbonyl Allylation via Alkyne-Alcohol C-C Bond Forming Transfer Hydrogenation: Allene Hydrometallation vs. Oxidative Coupling

    PubMed Central

    Liang, Tao; Nguyen, Khoa D.; Zhang, Wandi; Krische, Michael J.

    2015-01-01

    Chiral ruthenium(II) complexes modified by Josiphos ligands catalyze the reaction of alkynes with primary alcohols to form homoallylic alcohols with excellent control of regio-, diastereo- and enantioselectivity. These processes represent the first examples of enantioselective carbonyl allylation using alkynes as allylmetal equivalents. PMID:25734220

  17. Pyridine synthesis by reactions of allyl amines and alkynes proceeding through a Cu(OAc)2 oxidation and Rh(III)-catalyzed N-annulation sequence.

    PubMed

    Kim, Dong-Su; Park, Jung-Woo; Jun, Chul-Ho

    2012-11-28

    A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne. PMID:23069867

  18. Synthesis of 1,3-Amino Alcohols, 1,3-Diols, Amines, and Carboxylic Acids from Terminal Alkynes.

    PubMed

    Zeng, Mingshuo; Herzon, Seth B

    2015-09-01

    The half-sandwich ruthenium complexes 1-3 activate terminal alkynes toward anti-Markovnikov hydration and reductive hydration under mild conditions. These reactions are believed to proceed via addition of water to metal vinylidene intermediates (4). The functionalization of propargylic alcohols by metal vinylidene pathways is challenging owing to decomposition of the starting material and catalytic intermediates. Here we show that catalyst 2 can be employed to convert propargylic alcohols to 1,3-diols in high yield and with retention of stereochemistry at the propargylic position. The method is also amenable to propargylic amine derivatives, thereby establishing a route to enantioenriched 1,3-amino alcohol products. We also report the development of formal anti-Markovnikov reductive amination and oxidative hydration reactions to access linear amines and carboxylic acids, respectively, from terminal alkynes. This chemistry expands the scope of products that can be prepared from terminal alkynes by practical and high-yielding metal-catalyzed methods. PMID:26203776

  19. Preparation of reactive fibre interfaces using multifunctional cellulose derivatives.

    PubMed

    Vega, Beatriz; Wondraczek, Holger; Bretschneider, Leonore; Näreoja, Tuomas; Fardim, Pedro; Heinze, Thomas

    2015-11-01

    Cellulose fibres have poor reactivity and limited potential for surface engineering with advanced chemical functionalization in water. In this work, cellulose fibres were decorated with azide functions by charge-directed self-assembly of a novel water-soluble multifunctional cellulose derivative yielding reactive fibres. Propargylamine and 1-ethynylpyrene were utilized as a proof of concept that alkyne molecules may react with the azide functions of the reactive fibres via copper(I)-catalyzed azide-alkyne Huisgen cycloaddition (CuAAc) reaction in mild conditions. Chemical characterization of the fibres was carried out using classical techniques such as Raman-, fluorescence-, and UV-vis spectroscopy. Among other techniques, time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray spectroscopy (XPS), two-photon microscopy (TPM), and inductively coupled plasma mass spectrometry (ICP-MS) were useful tools for additional characterization of the fibres decorated with amino- or photoactive groups. The information gathered in this work might contribute to the basis for the preparation of reactive cellulose-based interfaces with potential application in CuAAc reactions. PMID:26256349

  20. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies.

    PubMed

    Ta, Duy Tien; Guedens, Wanda; Vranken, Tom; Vanschoenbeek, Katrijn; Steen Redeker, Erik; Michiels, Luc; Adriaensens, Peter

    2016-01-01

    Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets-a must for the development of advanced miniaturized, multi-biomarker biosensor platforms. PMID:27399790

  1. Carboxylation of terminal alkynes with CO2 using novel silver N-heterocyclic carbene complexes.

    PubMed

    Li, Shanshan; Sun, Jing; Zhang, Zhizhi; Xie, Ruixia; Fang, Xiangchen; Zhou, Mingdong

    2016-06-28

    Four novel N-heterocyclic carbene (NHC) silver complexes, , have been synthesized and characterized. The single X-ray crystal diffraction data indicate a dinuclear solid-state structure for and and a mononuclear structure for and . These complexes have been successfully used as efficient catalysts for the C-H activating carboxylation of terminal alkynes with CO2. A wide range of substrates with various functional groups afforded the corresponding aryl or alkyl substituted propiolic acids in good yields under mild conditions. Moreover, the role of bases and the reaction mechanism is thoroughly discussed. PMID:27263977

  2. Luminescent Alkyne-Bearing Terbium(III) Complexes and Their Application to Bioorthogonal Protein Labeling.

    PubMed

    O'Malley, William I; Abdelkader, Elwy H; Aulsebrook, Margaret L; Rubbiani, Riccardo; Loh, Choy-Theng; Grace, Michael R; Spiccia, Leone; Gasser, Gilles; Otting, Gottfried; Tuck, Kellie L; Graham, Bim

    2016-02-15

    Two new bifunctional macrocyclic chelate ligands that form luminescent terbium(III) complexes featuring an alkyne group for conjugation to (bio)molecules via the Cu(I)-catalyzed "click" reaction were synthesized. Upon ligation, the complexes exhibit a significant luminescent enhancement when excited at the λ(max) of the "clicked" products. To demonstrate the utility of the complexes for luminescent labeling, they were conjugated in vitro to E. coli aspartate/glutamate-binding protein incorporating a genetically encoded p-azido-L-phenylalanine or p-(azidomethyl)-L-phenylalanine residue. The complexes may prove useful for time-gated assay applications. PMID:26821062

  3. Synthesis of Cyclic Porphyrin Trimers through Alkyne Metathesis Cyclooligomerization and Their Host-Guest Binding Study.

    PubMed

    Yu, Chao; Long, Hai; Jin, Yinghua; Zhang, Wei

    2016-06-17

    Cyclic porphyrin trimers were synthesized through one-step cyclooligomerization via alkyne metathesis from diyne monomers. These macrocycles show interesting host-guest binding interactions with fullerenes, selectively binding C70 (6 × 10(3) M(-1)) over C60 and C84 (no binding observed). The fullerene-encapsulated host-guest complex can undergo guest or host exchange in the presence of another guest (2,4,6-tri(4-pyridyl)-1,3,5-triazine) or host (cage COP5) molecule with higher binding affinity. PMID:27267936

  4. Selective oxygenation of alkynes: a direct approach to diketones and vinyl acetate.

    PubMed

    Xia, Xiao-Feng; Gu, Zhen; Liu, Wentao; Wang, Ningning; Wang, Haijun; Xia, Yongmei; Gao, Haiyan; Liu, Xiang

    2014-12-28

    Arylalkynes can be converted into α-diketones with the use of a copper catalyst, and also be transformed into vinyl acetates under metal-free conditions, both in the presence of PhI(OAc)2 as an oxidant at room temperature. A series of substituted α-diketones were prepared in moderate to good yields. A variety of vinyl halides could be regio- and stereo-selectively synthesized under mild conditions, and I, Br and Cl could be all easily embedded into the alkynes. PMID:25356631

  5. An Alkyne Hydrosilylation-Oxidation Strategy for the Selective Installation of Oxygen Functionality

    PubMed Central

    Trost, Barry M.; Ball, Zachary T.; Laemmerhold, Kai M.

    2008-01-01

    Alkynes bearing propargylic, homopropargylic, and bis-homopropargylic hydroxyl groups are shown to serve as precursors for ketone or α-hydroxy ketone functionality. The approach hinges on the intermediacy of vinylsilanes created through regioselective hydrosilylation catalyzed by the complex [Cp*Ru(MeCN)3]PF6. Several oxidative pathways of linear and cyclic vinylsilanes are studied, and the possibility of diastereoselective epoxidation of cyclic vinylsilanes is demonstrated. The sequences constitute the equivalent of stereoselective aldol, homo-aldol, and bishomo-aldol type processes. The method is applied to a short synthesis of the piperidine alkaloid, spectaline. PMID:16011365

  6. Palladium-Catalyzed Annulation of Internal Alkynes: Direct Access to π-Conjugated Ullazines.

    PubMed

    Wan, Danyang; Li, Xiaoyu; Jiang, Ruyong; Feng, Boya; Lan, Jingbo; Wang, Ruilin; You, Jingsong

    2016-06-17

    A palladium-catalyzed cyclization reaction of 1-(2,6-dibromophenyl)-1H-pyrroles with alkynes has been developed to construct various π-conjugated indolizino[6,5,4,3-ija]quinolones (ullazines) with a reactive functional group tolerance. As illustrative examples, three new ullazine-based sensitizers are synthesized, and the performance of these dyes is examined in DSSC devices, which demonstrates the potential of direct C-H functionalization in the construction of organic optoelectronic materials. PMID:27227659

  7. The stereoselective synthesis of α-amino aldols starting from terminal alkynes.

    PubMed

    Miura, Tomoya; Nakamuro, Takayuki; Hiraga, Kentaro; Murakami, Masahiro

    2014-09-18

    A new procedure for the stereoselective synthesis of syn α-amino β-oxy ketones is reported. It consists of two steps; in the first step, α-amino silyl enol ethers having a (Z) geometry are prepared from 1-alkynes via 1-sulfonyl-1,2,3-triazoles. In the second step, the silyl enol ethers undergo the TiCl4-mediated Mukaiyama aldol reaction with aldehydes to produce α-amino β-oxy ketones with excellent syn-selectivity. PMID:25068433

  8. Amide-Directed Formation of Five-Coordinate Osmium Alkylidenes from Alkynes

    PubMed Central

    2015-01-01

    The amide-directed synthesis of five-coordinate osmium alkylidene derivatives from alkynes is reported. These types of complexes, which have been elusive until now because of the tendency of osmium to give hydride alkylidyne species, are prepared by reaction of the dihydride OsH2Cl2(PiPr3)2 (1) with terminal alkynes containing a distal amide group. Complex 1 reacts with N-phenylhex-5-ynamide and N-phenylhepta-6-ynamide to give OsCl2{=C(CH3)(CH2)nNH(CO)Ph}(PiPr3)2 (n = 3 (2), 4 (3)). The relative position of carbonyl and NH groups in the organic substrates has no influence on the reaction. Thus, treatment of 1 with N-(pent-4-yn-1-yl)benzamide leads to OsCl2{=C(CH3)(CH2)3NHC(O)Ph}(PiPr3)2 (4). The new compounds are intermediate species in the cleavage of the C–C triple bond of the alkynes. Under mild conditions, they undergo the rupture of the Cα–CH3 bond of the alkylidene, which comes from the alkyne triple bond, to afford six-coordinate hydride–alkylidyne derivatives. In dichloromethane, complex 2 gives a 10:7 mixture of OsHCl2{≡C(CH2)3C(O)NHPh}(PiPr3)2 (5) and OsHCl2{≡CCH(CH3)(CH2)2C(O)NHPh}(PiPr3)2 (6). The first complex contains a linear separation between the alkylidyne Cα atom and the amide group, whereas the spacer is branched in the second complex. In contrast to the case for 2, complex 4 selectively affords OsHCl2{≡C(CH2)3NHC(O)Ph}(PiPr3)2 (7). In spite of their instability, these compounds give the alkylidene–allene metathesis, being a useful entry to five-coordinate vinylidene complexes, including the dicarbon-disubstituted OsCl2(=C=CMe2)(PiPr3)2 (8) and the monosubstituted OsCl2(=C=CHCy)(PiPr3)2 (9). PMID:26877575

  9. General Method for the Preparation of Alkyne-Functionalized Oligopyridine Building Blocks.

    PubMed

    Ziessel, Raymond; Suffert, Jean; Youinou, Marie-Thérèse

    1996-09-20

    A large series of alkyne-substituted oligopyridines based on 2,2'-bipyridine, 1,10-phenanthroline, 2,2':6',2"-terpyridine, or 1,8-naphthyridine substrates has been synthesized and fully characterized. The palladium(0)-catalyzed coupling of bromo- or chloro-substituted derivatives with (trimethylsilyl)acetylene proceeds readily in diisopropylamine under ambient conditions giving good yields of the corresponding alkyne-substituted substrates oligoPy(C&tbd1;C)SiMe(3). The terminal monoynes oligoPyC&tbd1;CH become available upon treatment with K(2)CO(3) in methanol. Stepwise homologation of the acetylene function by Cadiot-Chodkiewicz coupling of oligoPyC&tbd1;CH with (bromoethynyl)triethylsilane (BrC&tbd1;CSiEt(3)) affords, in good yield, the silylated diynes oligoPy(C&tbd1;C)(2)SiEt(3), from which the terminal diynes oligoPy(C&tbd1;C)(2)H are formed by treatment with aqueous methanolic alkali. Reaction of oligoPy(C&tbd1;C)(2)H with BrC&tbd1;CSiEt(3) yields the silylated triynes oligoPy(C&tbd1;C)(3)SiEt(3) in modest yield. Further homologation is limited by nucleophilic attack of n-propylamine at the C-2 carbon of the alkyne chain, giving rise to a mixture of cis/cis (48%), cis/trans (33%), and trans/trans (19%) enaminediyne compounds 21a-c. Glaser oxidative self-coupling of the terminal diynes provides access to ditopic bipyridine or terpyridine ligands oligoPy(C&tbd1;C)(4)oligoPy comprising a tetrayne spacer. Quantitative formation of air-stable copper(I) complexes is described for the 6,6'-substituted ligands. A single crystal X-ray structure of complex 22a shows that the two ligands are interlocked around the copper(I) center in a pseudotetrahedral arrangement, similar to the structure deduced from NMR and FAB(+) data. The synthetic methods reported herein represent a valuable approach to the large-scale preparation of alkyne-functionalized oligopyridines. PMID:11667517

  10. Ni(II) salts and 2-propanol effect catalytic reductive coupling of epoxides and alkynes.

    PubMed

    Beaver, Matthew G; Jamison, Timothy F

    2011-08-01

    A Ni-catalyzed reductive coupling of alkynes and epoxides using Ni(II) salts and simple alcohol reducing agents is described. Whereas previously reported conditions relied on Ni(cod)(2) and Et(3)B, this system has several advantages including the use of air-stable and inexpensive Ni(II) precatalysts (e.g., NiBr(2)·3H(2)O) as the source of Ni(0) and simple alcohols (e.g., 2-propanol) as the reducing agent. Deuterium-labeling experiments are consistent with oxidative addition of an epoxide C-O bond that occurs with inversion of configuration. PMID:21718038

  11. Silver-Mediated anti-Markovnikov and Markovnikov-Selective Hydrotrifluoromethylthiolation of Terminal Alkynes.

    PubMed

    Wu, Wei; Dai, Wenpeng; Ji, Xinfei; Cao, Song

    2016-06-17

    The first example of direct hydrotrifluoromethylthiolation of terminal alkynes in the presence of AgSCF3 and K2S2O8 was established for the synthesis of a variety of vinyl trifluoromethyl thioethers. The anti-Markovnikov and Markovnikov adducts were obtained in moderate to good yields via two different reaction systems. Studies to probe the mechanism of the anti-Markovnikov addition reactions including the radical trapping experiments, kinetic isotope effect experiments, and deuterated experiments for determination of H-sources were conducted. PMID:27227878

  12. Inhibitory Effects of C2 to C10 1-Alkynes on Ammonia Oxidation in Two Nitrososphaera Species

    PubMed Central

    Taylor, K.; Tennigkeit, B.; Palatinszky, M.; Stieglmeier, M.; Myrold, D. D.; Schleper, C.; Wagner, M.; Bottomley, P. J.

    2015-01-01

    A previous study showed that ammonia oxidation by the Thaumarchaeota Nitrosopumilus maritimus (group 1.1a) was resistant to concentrations of the C8 1-alkyne, octyne, which completely inhibits activity by ammonia-oxidizing bacteria. In this study, the inhibitory effects of octyne and other C2 to C10 1-alkynes were evaluated on the nitrite production activity of two pure culture isolates from Thaumarchaeota group 1.1b, Nitrososphaera viennensis strain EN76 and Nitrososphaera gargensis. Both N. viennensis and N. gargensis were insensitive to concentrations of octyne that cause complete and irreversible inactivation of nitrite production by ammonia-oxidizing bacteria. However, octyne concentrations (≥20 μM) that did not inhibit N. maritimus partially inhibited nitrite production in N. viennensis and N. gargensis in a manner that did not show the characteristics of irreversible inactivation. In contrast to previous studies with an ammonia-oxidizing bacterium, Nitrosomonas europaea, octyne inhibition of N. viennensis was: (i) fully and immediately reversible, (ii) not competitive with NH4+, and (iii) without effect on the competitive interaction between NH4+ and acetylene. Both N. viennensis and N. gargensis demonstrated the same overall trend in regard to 1-alkyne inhibition as previously observed for N. maritimus, being highly sensitive to ≤C5 alkynes and more resistant to longer-chain length alkynes. Reproducible differences were observed among N. maritimus, N. viennensis, and N. gargensis in regard to the extent of their resistance/sensitivity to C6 and C7 1-alkynes, which may indicate differences in the ammonia monooxygenase binding and catalytic site(s) among the Thaumarchaeota. PMID:25576608

  13. Synthesis and cytotoxicity evaluation of aryl triazolic derivatives and their hydroxymethine homologues against B16 melanoma cell line.

    PubMed

    Kalhor-Monfared, Shiva; Beauvineau, Claire; Scherman, Daniel; Girard, Christian

    2016-10-21

    In this manuscript we describe synthesis and cytotoxicity evaluation of some triazolic derivatives against B16 melanoma cell line. For this purpose, we transformed a set of aromatic aldehydes into terminal alkynes, using Besthmann-Ohira reagent, and we made the corresponding hydroxymethyl homologated alkynes by an acetylene Grignard reagent. These generated two sets of alkynes were then subjected to a copper(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) using a solid-supported catalyst (Amberlyst A-21 CuI), with a third set composed of organic azides. Synthesized triazoles were then tested in vitro against B16 melanoma cell line. Amongst them, compounds a1b1 (R(1) = p-nitrophenyl, R(2) = benzyl), a4b1 (R(1) = naphthyl, R(2) = benzyl) and a4b5 (R(1) = naphthyl, R(2) = (R/S)- dioxolane) showed the best activity against B16 melanoma cells, with IC50 of 5.12, 3.89 and 6.60 μM respectively. PMID:27404558

  14. Regio- and Stereoselective Hydrosilylation of Unsymmetrical Alkynes Catalyzed by a Well-Defined, Low-Valent Cobalt Catalyst.

    PubMed

    Rivera-Hernández, Alejandro; Fallon, Brendan J; Ventre, Sandrine; Simon, Cédric; Tremblay, Marie-Hélène; Gontard, Geoffrey; Derat, Etienne; Amatore, Muriel; Aubert, Corinne; Petit, Marc

    2016-09-01

    Herein, the use of a well-defined low-valent cobalt(I) catalyst [HCo(PMe3)4] capable of performing the highly regio- and stereoselective hydrosilylation of internal alkynes is reported. The reaction can be applied to a variety of hydrosilanes, symmetrical and unsymmetrical alkynes, giving in many cases a single hydrosilylation isomer. Experimental and theoretical studies suggest the key step to be a hydro-cobaltation and that the reaction proceeds through a classical Chalk-Harrod mechanism. PMID:27552360

  15. Regioconvergent and Enantioselective Rhodium-Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles.

    PubMed

    Haydl, Alexander M; Hilpert, Lukas J; Breit, Bernhard

    2016-05-01

    The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes. PMID:26990445

  16. Transition metal-catalyzed couplings of alkynes to 1,3-enynes: modern methods and synthetic applications.

    PubMed

    Trost, Barry M; Masters, James T

    2016-04-21

    The metal-catalyzed coupling of alkynes is a powerful method for the preparation of 1,3-enynes, compounds that are of broad interest in organic synthesis. Numerous strategies have been developed for the homo- and cross coupling of alkynes to enynes via transition metal catalysis. In such reactions, a major issue is the control of regio-, stereo-, and, where applicable, chemoselectivity. Herein, we highlight prominent methods for the selective synthesis of these valuable compounds. Further, we illustrate the utility of these processes through specific examples of their application in carbocycle, heterocycle, and natural product syntheses. PMID:27086769

  17. Base-Free Direct Synthesis of Alkynylphosphonates from Alkynes and H-Phosphonates Catalyzed by Cu2O.

    PubMed

    Moglie, Yanina; Mascaró, Evangelina; Gutierrez, Victoria; Alonso, Francisco; Radivoy, Gabriel

    2016-03-01

    A simple and mild methodology for the direct synthesis of alkynylphosphonates is presented. The reaction of a variety of terminal alkynes with dialkyl phosphites in the presence Cu2O (14 mol %) led to the formation of the corresponding alkynylphosphonates in good to excellent yields. Reactions are performed under air, in acetonitrile as solvent, and in the absence of base or ligand additives. This new methodology is compatible with the presence of a wide variety of functional groups on the starting alkynes and can be scaled up to a gram scale. PMID:26839204

  18. Magnetic Hydrogels from Alkyne/Cobalt Carbonyl-Functionalized ABA Triblock Copolymers.

    PubMed

    Jiang, Bingyin; Hom, Wendy L; Chen, Xianyin; Yu, Pengqing; Pavelka, Laura C; Kisslinger, Kim; Parise, John B; Bhatia, Surita R; Grubbs, Robert B

    2016-04-01

    A series of alkyne-functionalized poly(4-(phenylethynyl)styrene)-block-poly(ethylene oxide)-block-poly(4-(phenylethynyl)styrene) (PPES-b-PEO-b-PPES) ABA triblock copolymers was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. PESn[Co2(CO)6]x-EO800-PESn[Co2(CO)6]x ABA triblock copolymer/cobalt adducts (10-67 wt % PEO) were subsequently prepared by reaction of the alkyne-functionalized PPES block with Co2(CO)8 and their phase behavior was studied by TEM. Heating triblock copolymer/cobalt carbonyl adducts at 120 °C led to cross-linking of the PPES/Co domains and the formation of magnetic cobalt nanoparticles within the PPES/Co domains. Magnetic hydrogels could be prepared by swelling the PEO domains of the cross-linked materials with water. Swelling tests, rheological studies and actuation tests demonstrated that the water capacity and modulus of the hydrogels were dependent upon the composition of the block copolymer precursors. PMID:26958699

  19. Initiator Control of Conjugated Polymer Topology in Ring-Opening Alkyne Metathesis Polymerization.

    PubMed

    von Kugelgen, Stephen; Bellone, Donatela E; Cloke, Ryan R; Perkins, Wade S; Fischer, Felix R

    2016-05-18

    Molybdenum carbyne complexes [RC≡Mo(OC(CH3)(CF3)2)3] featuring a mesityl (R = Mes) or an ethyl (R = Et) substituent initiate the living ring-opening alkyne metathesis polymerization of the strained cyclic alkyne, 5,6,11,12-tetradehydrobenzo[a,e][8]annulene, to yield fully conjugated poly(o-phenylene ethynylene). The difference in the steric demand of the polymer end-group (Mes vs Et) transferred during the initiation step determines the topology of the resulting polymer chain. While [MesC≡Mo(OC(CH3)(CF3)2)3] exclusively yields linear poly(o-phenylene ethynylene), polymerization initiated by [EtC≡Mo(OC(CH3)(CF3)2)3] results in cyclic polymers ranging in size from n = 5 to 20 monomer units. Kinetic studies reveal that the propagating species emerging from [EtC≡Mo(OC(CH3)(CF3)2)3] undergoes a highly selective intramolecular backbiting into the butynyl end-group. PMID:27120088

  20. Metal and carbene organocatalytic relay activation of alkynes for stereoselective reactions.

    PubMed

    Namitharan, Kayambu; Zhu, Tingshun; Cheng, Jiajia; Zheng, Pengcheng; Li, Xiangyang; Yang, Song; Song, Bao-An; Chi, Yonggui Robin

    2014-01-01

    Transition metal and organic catalysts have established their own domains of excellence. It has been expected that merging the two unique domains should provide complimentary or unprecedented opportunities in converting simple raw materials to functional products. N-heterocyclic carbenes alone are excellent organocatalysts. When used with transition metals such as copper, N-heterocyclic carbenes are routinely practiced as strong-coordinating ligands. Combination of an N-heterocyclic carbene and copper therefore typically leads to deactivation of either or both of the two catalysts. Here we disclose the direct merge of copper as a metal catalyst and N-heterocyclic carbenes as an organocatalyst for relay activation of alkynes. The reaction involves copper-catalysed activation of alkynes to generate ketenimine intermediates that are subsequently activated by an N-heterocyclic carbene organocatalyst for stereoselective reactions. Each of the two catalysts (copper metal catalyst and N-heterocyclic carbene organocatalyst) accomplishes its own missions in the activation steps without quenching each other. PMID:24865392

  1. Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities.

    PubMed

    Wang, Changhao; Carter-Cooper, Brandon; Du, Yixuan; Zhou, Jie; Saeed, Musabbir A; Liu, Jinbing; Guo, Min; Roembke, Benjamin; Mikek, Clinton; Lewis, Edwin A; Lapidus, Rena G; Sintim, Herman O

    2016-08-01

    G-quadruplex ligands have been touted as potential anticancer agents, however, none of the reported G-quadruplex-interactive small molecules have gone past phase II clinical trials. Recently it was revealed that diminazene (berenil, DMZ) actually binds to G-quadruplexes 1000 times better than DNA duplexes, with dissociation constants approaching 1 nM. DMZ however does not have strong anticancer activities. In this paper, using a panel of biophysical tools, including NMR, FRET melting assay and FRET competition assay, we discovered that monoamidine analogues of DMZ bearing alkyne substitutes selectively bind to G-quadruplexes. The lead DMZ analogues were shown to be able to target c-MYC G-quadruplex both in vitro and in vivo. Alkyne DMZ analogues display respectable anticancer activities (single digit micromolar GI50) against ovarian (OVCAR-3), prostate (PC-3) and triple negative breast (MDA-MB-231) cancer cell lines and represent interesting new leads to develop anticancer agents. PMID:27132164

  2. Hetero [6+3] cycloaddition of fulvenes with N-alkylidene glycine esters: a facile synthesis of the delavayine and incarvillateine framework.

    PubMed

    Hong, Bor-Cherng; Gupta, Arun Kumar; Wu, Ming-Fun; Liao, Ju-Hsiou; Lee, Gene-Hsiang

    2003-05-15

    [reaction: see text] In contrast to the [3+2] or [4+3] cycloaddition of N-metalated azomethine ylides and various alkenes, N-benzylidene glycine ethyl ester reacts with fulvenes to give the hetero [6+3] cycloaddition adducts with high stereoselectivity, constituting an efficient and novel route to [2]pyrindines. PMID:12735753

  3. Asymmetric synthesis of bicyclo[4.3.1]decadienes and bicyclo[3.3.2]decadienes via [6 + 3] trimethylenemethane cycloaddition with tropones.

    PubMed

    Trost, Barry M; McDougall, Patrick J; Hartmann, Olaf; Wathen, Peter T

    2008-11-12

    The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield. PMID:18937462

  4. Design of Redox/Radical Sensing Molecules via Nitrile Imine-Mediated Tetrazole-ene Cycloaddition (NITEC).

    PubMed

    Lederhose, Paul; Haworth, Naomi L; Thomas, Komba; Bottle, Steven E; Coote, Michelle L; Barner-Kowollik, Christopher; Blinco, James P

    2015-08-21

    The current study introduces a novel synthetic avenue for the preparation of profluorescent nitroxides via nitrile imine-mediated tetrazole-ene cycloaddition (NITEC). The photoinduced cycloaddition was performed under metal-free, mild conditions allowing the preparation of a library of the nitroxide functionalized pyrazolines and corresponding methoxyamines. High reaction rates and full conversion were observed, with the presence of the nitroxide having no significant impact on the cycloaddition performance. The formed products were investigated with respect to their photophysical properties in order to quantify their "switch on/off" behavior. The fluorescence quenching performance is strongly dependent on the distance between the chromophore and the free radical spin as demonstrated theoretically and experimentally. Highest levels of fluorescence quenching were achieved for pyrazolines with the nitroxide directly fused to the chromophore. Importantly, the pyrazoline profluorescent nitroxides were shown to efficiently act as sensors for redox/radical processes. PMID:26168007

  5. Theoretical studies of mechanisms of cycloaddition reaction between difluoromethylene carbene and acetone

    NASA Astrophysics Data System (ADS)

    Lu, Xiu Hui; Yu, Hai Bin; Wu, Wei Rong; Xu, Yue Hua

    Mechanisms of the cycloaddition reaction between singlet difluoromethylene carbene and acetone have been investigated with the second-order Møller-Plesset (MP2)/6-31G* method, including geometry optimization and vibrational analysis. Energies for the involved stationary points on the potential energy surface (PES) are corrected by zero-point energy (ZPE) and CCSD(T)/6-31G* single-point calculations. From the PES obtained with the CCSD(T)//MP2/6-31G* method for the cycloaddition reaction between singlet difluoromethylene carbene and acetone, it can be predicted that path B of reactions 2 and 3 should be two competitive leading channels of the cycloaddition reaction between difluoromethylene carbene and acetone. The former consists of two steps: (i) the two reactants first form a four-membered ring intermediate, INT2, which is a barrier-free exothermic reaction of 97.8 kJ/mol; (ii) the intermediate INT2 isomerizes to a four-membered product P2b via a transition state TS2b with an energy barrier of 24.9 kJ/mol, which results from the methyl group transfer. The latter proceeds in three steps: (i) the two reactants first form an intermediate, INT1c, through a barrier-free exothermic reaction of 199.4 kJ/mol; (ii) the intermediate INT1c further reacts with acetone to form a polycyclic intermediate, INT3, which is also a barrier-free exothermic reaction of 27.4 kJ/mol; and (iii) INT3 isomerizes to a polycyclic product P3 via a transition state TS3 with an energy barrier of 25.8 kJ/mol.

  6. Catalytic asymmetric reductive coupling of alkynes and aldehydes: enantioselective synthesis of allylic alcohols and alpha-hydroxy ketones.

    PubMed

    Miller, Karen M; Huang, Wei-Sheng; Jamison, Timothy F

    2003-03-26

    A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes is described. Allylic alcohols are afforded with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process is complementary to existing methods of enantioselective alpha-hydroxy ketone synthesis. PMID:12643701

  7. Direct and Base-Catalyzed Diboration of Alkynes Using the Unsymmetrical Diborane(4), pinB-BMes2.

    PubMed

    Kojima, Chiemi; Lee, Ka-Ho; Lin, Zhenyang; Yamashita, Makoto

    2016-05-25

    In the absence of transition metal catalysts, the unsymmetrical diborane(4), pinB-BMes2, reacted with alkynes to afford diborylalkenes. The isomer ratio of the products could be controlled via temperature, solvent, and additive(s). A reaction mechanism was proposed on the basis of two isolated intermediates, and this reaction could furthermore be applied to synthesize a luminescent molecule. PMID:27139814

  8. Magnetic Fe@g-C3N4: A Photoactive Catalyst for the Hydrogenation of Alkenes and Alkynes

    EPA Science Inventory

    A photoactive catalyst, Fe@g-C3N4, has been developed for the hydrogenation of alkenes and alkynes using hydrazine hydrate as a source of hydrogen. The magnetically separable Fe@g-C3N4 eliminates the use of high pressure hydrogenation and the reaction can be accomplished using vi...

  9. Alkyne-Modulated Surface-Enhanced Raman Scattering-Palette for Optical Interference-Free and Multiplex Cellular Imaging.

    PubMed

    Chen, Yong; Ren, Jia-Qiang; Zhang, Xia-Guang; Wu, De-Yin; Shen, Ai-Guo; Hu, Ji-Ming

    2016-06-21

    The alkyne tags possess unique interference-free Raman emissions but are still hindered for further application in the field of biochemical labels due to its extremely weak spontaneous Raman scattering. With the aid of computational chemistry, herein, an alkyne-modulated surface-enhanced Raman scattering (SERS) palette is constructed based on rationally designed 4-ethynylbenzenethiol derivatives for spectroscopic signature, Au@Ag core for optical enhancement and an encapsulating polyallylamine shell for protection and conjugation. Even for the pigment rich plant cell (e.g., pollen), the alkyne-coded SERS tag can be highly discerned on two-dimension distribution impervious to strong organic interferences originating from resonance-enhanced Raman scattering or autofluorescence. In addition, the alkynyl-containing Raman reporters contribute especially narrow emission, band shift-tunable (2100-2300 cm(-1)) and tremendously enhanced Raman signals when the alkynyl group locates at para position of mercaptobenzene ring. Depending on only single Raman band, the suggested alkyne-modulated SERS-palette potentially provides a more effective solution for multiplex cellular imaging with vibrant colors, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm(-1)) are inevitable under complex ambient conditions. PMID:27223333

  10. Ruthenium supported on magnetic nanoparticles: An efficient and recoverable catalyst for hydrogenation of alkynes and transfer hydrogenation of carbonyl compounds

    EPA Science Inventory

    Ruthenium supported on surface modified magnetic nanoparticles (NiFe2O4) has been successfully synthesized and applied for hydrogenation of alkynes at room temperature as well as transfer hydrogenation of a number of carbonyl compounds under microwave irradiation conditions. The ...

  11. Electrophilic Activation of P-Alkynes in the Synthesis of P-Substituted and P-Centered Heterocycles.

    PubMed

    Gupta, Akhil; Flynn, Bernard L

    2016-05-20

    Electrophilic activation of alkynylphosphine oxides and phosphonates provides a novel approach to the synthesis of P-substituted and P-centered heterocycles. Iodocyclization affords a heteroaryl iodide that can, among other things, be used in reiterative alkyne coupling and iodocyclization to give cyclic phosphonates and other cyclization reactions to give π-rich P-heterocycles. PMID:27088459

  12. Nano-copper catalysed highly regioselective synthesis of 2,4-disubstituted pyrroles from terminal alkynes and isocyanides.

    PubMed

    Tiwari, Dipak Kumar; Pogula, Jaya; Sridhar, B; Tiwari, Dharmendra Kumar; Likhar, Pravin R

    2015-09-14

    Nano-copper(0) stabilized on alumina prepared from Cu-Al hydrotalcite has been reported for completely regioselective synthesis of 2,4-disubstituted pyrroles from unactivated terminal aromatic/aliphatic alkynes and isocyanides. The reaction is operationally simple, involves ligand-free inexpensive nano-copper, and affords products in high yields. PMID:26226177

  13. Iron-copper cooperative catalysis in the reactions of alkyl Grignard reagents: exchange reaction with alkenes and carbometalation of alkynes.

    PubMed

    Shirakawa, Eiji; Ikeda, Daiji; Masui, Seiji; Yoshida, Masatoshi; Hayashi, Tamio

    2012-01-11

    Iron-copper cooperative catalysis is shown to be effective for an alkene-Grignard exchange reaction and alkylmagnesiation of alkynes. The Grignard exchange between terminal alkenes (RCH═CH(2)) and cyclopentylmagnesium bromide was catalyzed by FeCl(3) (2.5 mol %) and CuBr (5 mol %) in combination with PBu(3) (10 mol %) to give RCH(2)CH(2)MgBr in high yields. 1-Alkyl Grignard reagents add to alkynes in the presence of a catalyst system consisting of Fe(acac)(3), CuBr, PBu(3), and N,N,N',N'-tetramethylethylenediamine to give β-alkylvinyl Grignard reagents. The exchange reaction and carbometalation take place on iron, whereas copper assists with the exchange of organic groups between organoiron and organomagnesium species through transmetalation with these species. Sequential reactions consisting of the alkene-Grignard exchange and the alkylmagnesiation of alkynes were successfully conducted by adding an alkyne to a mixture of the first reaction. Isomerization of Grignard reagents from 2-alkyl to 1-alkyl catalyzed by Fe-Cu also is applicable as the first 1-alkyl Grignard formation step. PMID:22128888

  14. Microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne.

    PubMed

    Feng, Huangdi; Ermolat'ev, Denis S; Song, Gonghua; Van der Eycken, Erik V

    2011-09-16

    A novel and efficient microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne (OA(2)-coulpling) has been developed. This new multicomponent coupling constitutes an efficient approach for the synthesis of polysubstituted propargylamines in the presence of a catalytic amount of copper(I) catalyst. PMID:21823621

  15. Cu-catalyzed silylation of alkynes: a traceless 2-pyridylsulfonyl controller allows access to either regioisomer on demand.

    PubMed

    García-Rubia, Alfonso; Romero-Revilla, Jose A; Mauleón, Pablo; Gómez Arrayás, Ramón; Carretero, Juan C

    2015-06-01

    The Cu-catalyzed silylation of terminal and internal alkynes bearing a 2-pyridyl sulfonyl group (SO2Py) at the propargylic position affords a breadth of vinyl silanes in good yields and with excellent regio- and stereocontrol under mild conditions. The directing SO2Py group is essential in terms of reaction efficiency and chemoselectivity. Importantly, this group also provides the ability to reverse the regiochemical outcome of the reaction, opening the access to either regioisomer without modification of the starting substrate by virtue of an in situ base-promoted alkyne to allene equilibration which takes place prior to the silylcupration process. Furthermore, removal of the directing SO2Py allows for further elaboration of the silylation products. In particular, a one-pot tandem alkyne silylation/allylic substitution sequence, in which both steps are catalyzed by the same Cu species, opens up a new approach for the access to either formal hydrosilylation regioisomer of unsymmetrical aliphatic-substituted internal alkynes from propargyl sulfones. PMID:25955333

  16. Rh(iii)-catalyzed chemoselective C-H functionalizations of tertiary aniline N-oxides with alkynes.

    PubMed

    Huang, Xiaolei; Liang, Wenbo; Shi, Yang; You, Jingsong

    2016-05-01

    In this work, we report novel Rh(iii)-catalyzed chemoselective functionalizations of tertiary aniline N-oxides with alkynes, including annulation via the sequential C(sp(2))-H and C(sp(3))-N activation for the formation of N-alkylindoles and an O-atom transfer (OAT) process for the synthesis of acetophenones. PMID:27121366

  17. Tandem Copper-Catalyzed Propargylation/Alkyne Azacyclization/Isomerization Reaction under Microwave Irradiation: Synthesis of Fully Substituted Pyrroles.

    PubMed

    Zhang, Xiao-Yan; Yang, Zhi-Wei; Chen, Zhongzhu; Wang, Jun; Yang, Dong-Lin; Shen, Ze; Hu, Li-Li; Xie, Jian-Wu; Zhang, Jin; Cui, Hai-Lei

    2016-03-01

    A copper-catalyzed and microwave-assisted synthesis of fully substituted pyrroles has been developed. A series of pentasubstituted pyrroles, especially α-arylpyrroles, could be obtained in moderate to good yields (up to 93%) through a tandem propargylation/alkyne azacyclization/isomerization sequence from readily available β-enamino compounds and propargyl acetates. PMID:26872395

  18. Rhodium-Catalyzed Enantioselective Intermolecular Hydroalkoxylation of Allenes and Alkynes with Alcohols: Synthesis of Branched Allylic Ethers.

    PubMed

    Liu, Zi; Breit, Bernhard

    2016-07-11

    Regio- and enantioselective additions of alcohols to either terminal allenes or internal alkynes provides access to allylic ethers by using a Rh(I) /diphenyl phosphate catalytic system. This method provides an atom-economic way to obtain chiral aliphatic and aryl allylic ethers in moderate to good yield with good to excellent enantioselectivities. PMID:27244349

  19. The Structure of SpnF, a Standalone Enzyme that Catalyzes [4+2] Cycloaddition

    PubMed Central

    Fage, Christopher D.; Isiorho, Eta A.; Liu, Yungnan; Wagner, Drew T.; Liu, Hung-wen; Keatinge-Clay, Adrian T.

    2015-01-01

    In the biosynthetic pathway of the spinosyn insecticides, the tailoring enzyme SpnF performs a [4+2]-cycloaddition on a 22-membered macrolactone to forge an embedded cyclohexene ring. To learn more about this reaction, which could potentially proceed through a Diels-Alder mechanism, the 1.50 Å-resolution crystal structure of SpnF bound to S-adenosylhomocysteine (SAH) was determined. This sets the stage for advanced experimental and computational studies to determine the precise mechanism of SpnF-mediated cyclization. PMID:25730549

  20. The structure of SpnF, a standalone enzyme that catalyzes [4 + 2] cycloaddition.

    PubMed

    Fage, Christopher D; Isiorho, Eta A; Liu, Yungnan; Wagner, Drew T; Liu, Hung-wen; Keatinge-Clay, Adrian T

    2015-04-01

    In the biosynthetic pathway of the spinosyn insecticides, the tailoring enzyme SpnF performs a [4 + 2] cycloaddition on a 22-membered macrolactone to forge an embedded cyclohexene ring. To learn more about this reaction, which could potentially proceed through a Diels-Alder mechanism, we determined the 1.50-Å-resolution crystal structure of SpnF bound to S-adenosylhomocysteine. This sets the stage for advanced experimental and computational studies to determine the precise mechanism of SpnF-mediated cyclization. PMID:25730549

  1. Palladium-Catalyzed Diastereo- and Enantioselective Formal [3+2]-Cycloadditions of Substituted Vinylcyclopropanes

    PubMed Central

    Trost, Barry M.; Morris, Patrick J.; Sprague, Simon J.

    2012-01-01

    We describe a palladium-catalyzed diastereo- and enantioselective formal [3+2]-cycloaddition between substituted vinyl-cyclopropanes and electron deficient olefins in the form of azlactone- and Meldrum’s acid alkylidenes to give highly-substituted cyclo-pentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle. PMID:23030714

  2. Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition.

    PubMed

    Desbois, Nicolas; Pacquelet, Sandrine; Dubois, Adrien; Michelin, Clément; Gros, Claude P

    2015-01-01

    The Cu(I)-catalysed Huisgen cycloaddition, known as "click" reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one "cold" metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI. PMID:26664643

  3. Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

    PubMed Central

    Desbois, Nicolas; Pacquelet, Sandrine; Dubois, Adrien; Michelin, Clément

    2015-01-01

    Summary The Cu(I)-catalysed Huisgen cycloaddition, known as “click” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI. PMID:26664643

  4. Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

    PubMed Central

    Okkel, Andreas; Schwach, Lukas; Wagner, Laura; Selig, Anja; Prokop, Aram

    2014-01-01

    Summary An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute ‘second-generation’ functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity. PMID:25161720

  5. Silver Nanoparticle-Catalyzed Diels-Alder Cycloadditions of 2′-Hydroxychalcones

    PubMed Central

    Cong, Huan; Becker, Clinton F.; Elliott, Sean J.; Grinstaff, Mark W.; Porco, John A.

    2010-01-01

    Metal nanoparticles are currently being employed as catalysts for a number of classical chemical transformations. In contrast, identification of novel reactions of nanoparticles, especially towards the synthesis of complex natural products and derivatives, is highly underdeveloped and represents a bourgeoning area in chemical synthesis. Herein, we report silica-supported silver nanoparticles as solid, recyclable catalysts for Diels-Alder cycloadditions of 2′-hydroxychalcones and dienes in high yield and turnover number. The use of silver nanoparticle catalysts is further demonstrated by the total synthesis of the cytotoxic natural product panduratin A employing a highly electron-rich dienophile and Lewis acid-sensitive diene. PMID:20443601

  6. Allenes as three-carbon units in catalytic cycloadditions: new opportunities with transition-metal catalysts.

    PubMed

    López, Fernando; Mascareñas, José Luis

    2011-01-10

    Allenes are very versatile synthetic units that are used in many types of catalytic cycloaddition reactions. Most examples reported so far involve their use as 2C-atom components, whereas their participations as 3C-atom components have been much less frequent. In this concept article, we present an overview of this latter strategy, emphasizing on those more recent contributions involving the use of Pt(II) and Au(I) catalysts, which have uncovered new opportunities in this area. PMID:21207554

  7. Enantioselective Cycloaddition of Münchnones onto [60]Fullerene: Organocatalysis versus Metal Catalysis

    PubMed Central

    2014-01-01

    Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of münchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complementary in the synthesis of optically active pyrrolino[3,4:1,2][60]fullerenes with high levels of enantiomeric excess and moderate to good conversions. Further functionalization of the pyrrolinofullerene carboxylic acid derivatives has been carried out by esterification and amidation reactions. PMID:24483247

  8. Chiral Phosphate in Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition: Ligand, Counterion, or Both?

    PubMed

    Barbazanges, Marion; Caytan, Elsa; Lesage, Denis; Aubert, Corinne; Fensterbank, Louis; Gandon, Vincent; Ollivier, Cyril

    2016-06-13

    Investigations based on NMR spectroscopy, mass spectrometry, and DFT calculations shed light on the metallic species generated in the rhodium-catalyzed asymmetric [2+2+2] cycloaddition reaction between diynes and isocyanates with the chiral phosphate TRIP. The catalytic mixture comprising [{Rh(cod)Cl}2 ], 1,4-diphenylphosphinobutane (dppb), and Ag(S)-TRIP actually gives rise to two species, both having an effect on the stereoselectivity. One is a rhodium(I) complex in which TRIP is a weakly coordinating counterion, whereas the other is a bimetallic Rh/Ag complex in which TRIP is a strongly coordinating X-type ligand. PMID:27167983

  9. Synthesis of Cyclic Azomethine Imines by Cycloaddition Reactions of N-Isocyanates and N-Isothiocyanates.

    PubMed

    Bongers, Amanda; Ranasinghe, Indee; Lemire, Philippe; Perozzo, Alyssa; Vincent-Rocan, Jean-François; Beauchemin, André M

    2016-08-01

    Various nitrogen-substituted iso(thio)cyanates engage in [3 + 2]-cycloaddition reactions to form azomethine imines containing triazolone, triazole-thione, and pyrazole-thione cores. First, iminoisothiocyanates are shown to undergo aminothiocarbonylation reactions with strained alkenes, and a comparison with recently reported reactions of iminoisocyanates highlights their reduced reactivity. In contrast, amino(thio)carbonylation reactions of imines with iminoisocyanates and iminoisothiocyanates proved more efficient, providing access to triazolone and triazole-thione cores. The dipole products can be converted to valuable heterocyclic cores through simple derivatization reactions. PMID:27458786

  10. Sterically controlled azomethine ylide cycloaddition polymerization of phenyl-C61-butyric acid methyl ester.

    PubMed

    Stephen, Meera; Ramanitra, Hasina H; Santos Silva, Hugo; Dowland, Simon; Bégué, Didier; Genevičius, Kristijonas; Arlauskas, Kęstutis; Juška, Gytis; Morse, Graham E; Distler, Andreas; Hiorns, Roger C

    2016-05-01

    Phenyl-C61-butyric acid methyl ester (PCBM) is polymerized simply using a one-pot reaction to yield soluble, high molecular weight polymers. The sterically controlled azomethine ylide cycloaddition polymerization (SACAP) is demonstrated to be highly adaptable and yields polymers with probable Mn≈ 24 600 g mol(-1) and Mw≈ 73 800 g mol(-1). Products are metal-free and of possible benefit to organic and hybrid photovoltaics and electronics as they form thin films from solution and have raised LUMOs. The promising electronic properties of this new polymer are discussed. PMID:27066898

  11. Asymmetric Isothiourea-Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines

    PubMed Central

    Smith, Siobhan R; Fallan, Charlene; Taylor, James E; McLennan, Ross; Daniels, David S B; Morrill, Louis C; Slawin, Alexandra M Z; Smith, Andrew D

    2015-01-01

    A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high d.r., yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks. PMID:26073559

  12. Synthesis of Functionalized Organotrifluoroborates via the 1,3-Dipolar Cycloaddition of Azides

    PubMed Central

    Molander, Gary A.; Ham, Jungyeob

    2008-01-01

    We have successfully prepared potassium azidoalkyltrifluoroborates from the corresponding halogen compounds in 94–98% yields through a nucleophilic substitution reaction with NaN3. In the presence of various alkynes and CuI as a catalyst, these azidotrifluoroborates easily formed 1,4-disubstituted organo-[1,2,3]-triazol-1-yl-trifluoroborates in 85–98% yields. This method was then developed into a facile one-pot synthesis for the preparation of various organo-[1,2,3]-triazol-1-yl-trifluoroborates using haloalkyltrifluoroborates as the starting materials. PMID:16774252

  13. Microwave-Based Reaction Screening: Tandem Retro-Diels-Alder/Diels-Alder Cycloadditions of ortho-Quinol Dimers

    PubMed Central

    Dong, Suwei; Cahill, Kath arine J.; Kang, Moon -Il; Colburn, Nancy H.; Henrich, Curtis J.; Wilson, Jennifer A.; Beutler, John A.; Johnson, Richard P.; Porco, John A.

    2011-01-01

    We have accomplished a parallel screen of cycloaddition partners for ortho-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels-Alder/Diels-Alder cascades of ortho-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels-Alder cycloadditions of ortho-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor. PMID:21942286

  14. Metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides: a practical access to piperidine-fused bicyclic heterocycles.

    PubMed

    Liu, Honglei; Wu, Yang; Zhao, Yan; Li, Zhen; Zhang, Lei; Yang, Wenjun; Jiang, Hui; Jing, Chengfeng; Yu, Hao; Wang, Bo; Xiao, Yumei; Guo, Hongchao

    2014-02-12

    The first metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides has been developed. With the use of a chiral ferrocenylphosphine-copper(I) complex as the catalyst, the asymmetric variant of the [6 + 3] cycloaddition has also been successfully achieved. The reactions proceeded smoothly under mild conditions, affording piperidine-fused bicyclic heterocycles in moderate to high yields with good to excellent diastereo- and enantioselectivies. The procedures are operationally simple and the catalysts are cheap and readily accessible, thus providing a practical approach to piperidine-fused bicyclic heterocycles. PMID:24450417

  15. Synthesis of molybdenum nitrido complexes for triple-bond metathesis of alkynes and nitriles.

    SciTech Connect

    Wiedner, E. S.; Gallagher, K. J.; Johnson, M. A.; Kampf, J. W.

    2011-06-04

    Complexes of the type N {triple_bond} Mo(OR){sub 3} (R = tertiary alkyl, tertiary silyl, bulky aryl) have been synthesized in the search for molybdenum-based nitrile-alkyne cross-metathesis (NACM) catalysts. Protonolysis of known N {triple_bond} Mo(NMe{sub 2}){sub 3} led to the formation of N {triple_bond} Mo(O-2,6-{sup i}Pr{sub 2}C{sub 6}H{sub 3}){sub 3}(NHMe{sub 2}) (12), N {triple_bond} Mo(OSiPh{sub 3}){sub 3}(NHMe{sub 2}) (5-NHMe{sub 2}), and N {triple_bond} Mo(OCPh{sub 2}Me){sub 3}(NHMe{sub 2}) (17-NHMe{sub 2}). The X-ray structure of 12 revealed an NHMe{sub 2} ligand bound cis to the nitrido ligand, while 5-NHMe{sub 2} possessed an NHMe{sub 2} bound trans to the nitride ligand. Consequently, 17-NHMe{sub 2} readily lost its amine ligand to form N {triple_bond} Mo(OCPh{sub 2}Me){sub 3} (17), while 12 and 5-NHMe{sub 2} retained their amine ligands in solution. Starting from bulkier tris-anilide complexes, N {triple_bond} Mo(N[R]Ar){sub 3} (R = isopropyl, tert-butyl; Ar = 3,5-dimethylphenyl) allowed for the formation of base-free complexes N {triple_bond} Mo(OSiPh3)3 (5) and N {triple_bond} Mo(OSiPh{sub 2}tBu){sub 3} (16). Achievement of a NACM cycle requires the nitride complex to react with alkynes to form alkylidyne complexes; therefore the alkyne cross-metathesis (ACM) activity of the complexes was tested. Complex 5 was found to be an efficient catalyst for the ACM of 1-phenyl-1-butyne at room temperature. Complexes 12 and 5-NHMe{sub 2} were also active for ACM at 75 C, while 17-NHMe{sub 2} and 16 did not show ACM activity. Only 5 proved to be active for the NACM of anisonitrile, which is a reactive substrate in NACM catalyzed by tungsten. NACM with 5 required a reaction temperature of 180 C in order to initiate the requisite alkylidyne-to-nitride conversion, with slightly more than two turnovers achieved prior to catalyst deactivation. Known molybdenum nitrido complexes were screened for NACM activity under similar conditions, and only N {triple_bond} Mo

  16. Rh-Catalyzed Decarbonylation of Conjugated Ynones via Carbon–Alkyne Bond Activation: Reaction Scope and Mechanistic Exploration via DFT Calculations

    PubMed Central

    Dermenci, Alpay; Whittaker, Rachel E.; Gao, Yang; Cruz, Faben A.; Yu, Zhi-Xiang; Dong, Guangbin

    2015-01-01

    In this full article, detailed development of a catalytic decarbonylation of conjugated monoynones to synthesize disubstituted alkynes is described. The reaction scope and limitation has been thoroughly investigated, and a broad range of functional groups including heterocycles were compatible under the catalytic conditions. Mechanistic exploration via DFT calculations has also been executed. Through the computational study, a proposed catalytic mechanism has been carefully evaluated. These efforts are expected to serve as an important exploratory study for developing catalytic alkyne-transfer reactions via carbon−alkyne bond activation. PMID:26229587

  17. Synthesis of Stable Interfaces on SnO2 Surfaces for Charge-Transfer Applications

    NASA Astrophysics Data System (ADS)

    Benson, Michelle C.

    The commercial market for solar harvesting devices as an alternative energy source requires them to be both low-cost and efficient to replace or reduce the dependence on fossil fuel burning. Over the last few decades there has been promising efforts towards improving solar devices by using abundant and non-toxic metal oxide nanomaterials. One particular metal oxide of interest has been SnO2 due to its high electron mobility, wide-band gap, and aqueous stability. However SnO2 based solar cells have yet to reach efficiency values of other metal oxides, like TiO2. The advancement of SnO2 based devices is dependent on many factors, including improved methods of surface functionalization that can yield stable interfaces. This work explores the use of a versatile functionalization method through the use of the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The CuAAC reaction is capable of producing electrochemically, photochemically, and electrocatalytically active surfaces on a variety of SnO2 materials. The resulting charge-transfer characteristics were investigated as well as an emphasis on understanding the stability of the resulting molecular linkage. We determined the CuAAC reaction is able to proceed through both azide-modified and alkyne-modified surfaces. The resulting charge-transfer properties showed that the molecular tether was capable of supporting charge separation at the interface. We also investigated the enhancement of electron injection upon the introduction of an ultra-thin ZrO2 coating on SnO2. Several complexes were used to fully understand the charge-transfer capabilities, including model systems of ferrocene and a ruthenium coordination complex, a ruthenium mononuclear water oxidation catalyst, and a commercial ruthenium based dye.

  18. 1,2,3-Triazole-Functionalized Polysulfone Synthesis through Microwave-Assisted Copper-Catalyzed Click Chemistry: A Highly Proton Conducting High Temperature Membrane.

    PubMed

    Sood, Rakhi; Donnadio, Anna; Giancola, Stefano; Kreisz, Aurélien; Jones, Deborah J; Cavaliere, Sara

    2016-07-01

    Microwave heating holds all the aces regarding development of effective and environmentally friendly methods to perform chemical transformations. Coupling the benefits of microwave-enhanced chemistry with highly reliable copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry paves the way for a rapid and efficient synthesis procedure to afford high performance thermoplastic materials. We describe herein fast and high yielding synthesis of 1,2,3-triazole-functionalized polysulfone through microwave-assisted CuAAC as well as explore their potential as phosphoric acid doped polymer electrolyte membranes (PEM) for high temperature PEM fuel cells. Polymers with various degrees of substitution of the side-chain functionality of 1,4-substituted 1,2,3-triazole with alkyl and aryl pendant structures are prepared by sequential chloromethylation, azidation, and microwave-assisted CuAAC using a range of alkynes (1-pentyne, 1-nonyne, and phenylacetylene). The completeness of reaction at each step and the purity of the clicked polymers were confirmed by (1)H-(13)C NMR, DOSY-NMR and FTIR-ATR spectroscopies. The thermal and thermochemical properties of the modified polymers were characterized by differential scanning calorimetry and thermogravimetric analysis coupled with mass spectroscopy (TG-MS), respectively. TG-MS analysis demonstrated that the commencement of the thermal degradation takes place with the decomposition of the triazole ring while its substituents have critical influence on the initiation temperature. Polysulfone functionalized with 4-phenyl-1,2,3-triazole demonstrates significantly higher Tg, Td, and elastic modulus than the ones bearing 4-propyl-1,2,3-triazole and 4-heptyl-1,2,3-triazole groups. After doping with phosphoric acid, the functionalized polymers with acid doping level of 5 show promising performance with high proton conductivity in anhydrous conditions (in the range of 27-35 mS/cm) and satisfactorily high elastic modulus (in the range

  19. Electrochemical Rectification of Redox Mediators Using Porphyrin-Based Molecular Multilayered Films on ITO Electrodes.

    PubMed

    Civic, Marissa R; Dinolfo, Peter H

    2016-08-10

    Electrochemical charge transfer through multilayer thin films of zinc and nickel 5,10,15,20-tetra(4-ethynylphenyl) porphyrin constructed via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry was examined. Current rectification toward various outer-sphere redox probes is revealed with increasing numbers of layers, as these films possess insulating properties over the neutral potential range of the porphyrin, then become conductive upon reaching its oxidation potential. Interfacial electron transfer rates of mediator-dye interactions toward [Co(bpy)3](2+), [Co(dmb)3](2+), [Co(NO2-phen)3](2+), [Fe(bpy)3](2+), and ferrocene (Fc), all outer-sphere redox species, were measured by hydrodynamic methods. The ability to modify electroactive films' interfacial electron transfer rates, as well as current rectification toward redox species, has broad applicability in a number of devices, particularly photovoltaics and photogalvanics. PMID:27410765

  20. Recyclable catalytic dendrimer nanoreactor for part-per-million Cu(I) catalysis of "click" chemistry in water.

    PubMed

    Deraedt, Christophe; Pinaud, Noël; Astruc, Didier

    2014-08-27

    Upon catalyst and substrate encapsulation, an amphiphilic dendrimer containing 27 triethylene glycol termini and 9 intradendritic triazole rings serves as a catalytic nanoreactor by considerably accelerating the Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) "click" reactions of various substrates in water using the catalyst Cu(hexabenzyltren)Br (tren = triaminoethylamine). Moreover this recyclable nanoreactor with intradendritic triazole rings strongly also activates the simple Sharpless-Fokin catalyst CuSO4 + sodium ascorbate in water under ambient conditions leading to exceptional TONs up to 510,000. This fully recyclable catalytic nanoreactor allows to considerably decrease the amount of this cheap copper catalyst down to industrially tolerable residues, and some biomedical and cosmetic applications are exemplified. PMID:25093967

  1. "Janus" Calixarenes: Double-Sided Molecular Linkers for Facile, Multianchor Point, Multifunctional, Surface Modification.

    PubMed

    Buttress, James P; Day, David P; Courtney, James M; Lawrence, Elliot J; Hughes, David L; Blagg, Robin J; Crossley, Alison; Matthews, Susan E; Redshaw, Carl; Bulman Page, Philip C; Wildgoose, Gregory G

    2016-08-01

    We herein report the synthesis of novel "Janus" calix[4]arenes bearing four "molecular tethering" functional groups on either the upper or lower rims of the calixarene. These enable facile multipoint covalent attachment to electrode surfaces with monolayer coverage. The other rim of the calixarenes bear either four azide or four ethynyl functional groups, which are easily modified by the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), either pre- or postsurface modification, enabling these conical, nanocavity reactor sites to be decorated with a wide range of substrates to impart desired chemical properties. Redox active species decorating the peripheral rim are shown to be electrically connected by the calixarene to the electrode surface in either "up" or "down" orientations of the calixarene. PMID:27419844

  2. Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations.

    PubMed

    Pecchioli, Tommaso; Muthyala, Manoj Kumar; Haag, Rainer; Christmann, Mathias

    2015-01-01

    The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. PMID:26150897

  3. Carbohydrate-Specific Uptake of Fucosylated Polymeric Micelles by Different Cancer Cell Lines.

    PubMed

    Babiuch, Krzysztof; Dag, Aydan; Zhao, Jiacheng; Lu, Hongxu; Stenzel, Martina H

    2015-07-13

    Inspired by upregulated levels of fucosylated proteins on the surfaces of multiple types of cancer cells, micelles carrying β-l-fucose and β-d-glucose were prepared. A range of block copolymers were synthesized by reacting a mixture of 2-azidoethyl β-l-fucopyranoside (FucEtN3) and 2-azideoethyl β-d-glucopyranoside (GlcEtN3) with poly(propargyl methacrylate)-block-poly(n-butyl acrylate) (PPMA-b-PBA) using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Five block copolymers were obtained ranging from 100 mol % fucose to 100% glucose functionalization. The resulting micelles had hydrodynamic diameters of around 30 nm. In this work, we show that fucosylated micelles reveal an increased uptake by pancreatic, lung, and ovarian carcinoma cell lines, whereas the uptake by the healthy cell lines (CHO) is negligible. This finding suggests that these micelles can be used for targeted drug delivery toward cancer cells. PMID:26057004

  4. Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II)-Phthalocyanines.

    PubMed

    Bächle, Felix; Hanack, Michael; Ziegler, Thomas

    2015-01-01

    In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of ¹H-NMR, 13C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were synthesized through a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The 2-methoxyethoxymethyl protecting group (MEM) was used to protect the carbohydrate moieties. It resisted the harsh basic cyclotetramerization conditions and could be easily cleaved under mild acidic conditions. The glycoconjugated zinc(II) phthalocyanines described here have molar extinction coefficents εmax>10⁵ m(-1) cm(-1) and absorption maxima λ>680 nm, which make them attractive photosensitizers for photo-dynamic therapy. PMID:26473808

  5. “Janus” Calixarenes: Double-Sided Molecular Linkers for Facile, Multianchor Point, Multifunctional, Surface Modification

    PubMed Central

    2016-01-01

    We herein report the synthesis of novel “Janus” calix[4]arenes bearing four “molecular tethering” functional groups on either the upper or lower rims of the calixarene. These enable facile multipoint covalent attachment to electrode surfaces with monolayer coverage. The other rim of the calixarenes bear either four azide or four ethynyl functional groups, which are easily modified by the copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC), either pre- or postsurface modification, enabling these conical, nanocavity reactor sites to be decorated with a wide range of substrates to impart desired chemical properties. Redox active species decorating the peripheral rim are shown to be electrically connected by the calixarene to the electrode surface in either “up” or “down” orientations of the calixarene. PMID:27419844

  6. Functional Biomimetic Architectures

    NASA Astrophysics Data System (ADS)

    Levine, Paul M.

    N-substituted glycine oligomers, or 'peptoids,' are a class of sequence--specific foldamers composed of tertiary amide linkages, engendering proteolytic stability and enhanced cellular permeability. Peptoids are notable for their facile synthesis, sequence diversity, and ability to fold into distinct secondary structures. In an effort to establish new functional peptoid architectures, we utilize the copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction to generate peptidomimetic assemblies bearing bioactive ligands that specifically target and modulate Androgen Receptor (AR) activity, a major therapeutic target for prostate cancer. Additionally, we explore chemical ligation protocols to generate semi-synthetic hybrid biomacromolecules capable of exhibiting novel structures and functions not accessible to fully biosynthesized proteins.

  7. Soluble organic nanotubes for catalytic systems.

    PubMed

    Xiong, Linfeng; Yang, Kunran; Zhang, Hui; Liao, Xiaojuan; Huang, Kun

    2016-03-18

    In this paper, we report a novel method for constructing a soluble organic nanotube supported catalyst system based on single-molecule templating of core–shell bottlebrush copolymers. Various organic or metal catalysts, such as sodium prop-2-yne-1-sulfonate (SPS), 1-(2-(prop-2-yn-1-yloxy)ethyl)-1H-imidazole (PEI) and Pd(OAc)2 were anchored onto the tube walls to functionalize the organic nanotubes via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Depending on the 'confined effect' and the accessible cavity microenvironments of tubular structures, the organic nanotube catalysts showed high catalytic efficiency and site-isolation features. We believe that the soluble organic nanotubes will be very useful for the development of high performance catalyst systems due to their high stability of support, facile functionalization and attractive textural properties. PMID:27308672

  8. Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3-Triazolylbenzyl-aminophosphonates.

    PubMed

    Ouahrouch, Abdelaaziz; Taourirte, Moha; Schols, Dominique; Snoeck, Robert; Andrei, Graciela; Engels, Joachim W; Lazrek, Hassan B

    2016-01-01

    A novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the Kabachnik-Fields reaction using I2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1) H NMR, (13) C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X-ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4. PMID:26575425

  9. Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3‐Triazolylbenzyl‐aminophosphonates

    PubMed Central

    Ouahrouch, Abdelaaziz; Taourirte, Moha; Schols, Dominique; Snoeck, Robert; Andrei, Graciela; Lazrek, Hassan B.

    2015-01-01

    A novel series of ribonucleosides of 1,2,3‐triazolylbenzyl‐aminophosphonates was synthesized through the Kabachnik–Fields reaction using I2 as catalyst followed by copper‐catalyzed cycloaddition of the azide–alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by 1H NMR, 13C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X‐ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4. PMID:26575425

  10. Influence of metallocene substitution on the antibacterial activity of multivalent peptide conjugates.

    PubMed

    Hoffknecht, Barbara C; Prochnow, Pascal; Bandow, Julia E; Metzler-Nolte, Nils

    2016-07-01

    Peptide dendrimers and derivatisation of peptides with metallocenes showed promising results in the search for new antibacterial agents. The two concepts are combined in this work leading to multivalent, metallocene-containing peptide derivates. These new peptides were synthesised utilising microwave assisted, copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click" chemistry). Twelve new peptide conjugates, containing either a ferrocenoyl group or a ruthenocenoyl group on so-called ultrashort (i.e. < 5 amino acids) peptides, and ranging from monovalent to trivalent conjugates, were synthesised and their antibacterial activity was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains. The antibacterial activity was compared to the same peptide conjugates without metallocenes. The resulting MIC values showed a significant enhancement of the antibacterial activity of these peptide conjugates against Gram-positive bacteria by the metallocenoyl groups. Additionally, the compounds with two metallocenoyl groups presented the best antibacterial activities overall. PMID:26988572

  11. Synthesis of Dihydropyridines and Pyridines from Imines and Alkynes via C-H Activation

    SciTech Connect

    Ellman, Jonathan A.; Colby, Denise; Bergman, Robert

    2007-11-20

    A convenient one-pot C-H alkenylation/electrocyclization/aromatization sequence has been developed for the synthesis of highly substituted pyridine derivatives from alkynes and {alpha},{beta}-unsaturated N-benzyl aldimines and ketimines that proceeds through dihydropyridine intermediates. A new class of ligands for C-H activation was developed, providing broader scope for the alkenylation step than could be achieved with previously reported ligands. Substantial information was obtained about the mechanism of the reaction. This included the isolation of a C-H activated complex and its structure determination by X-ray analysis; in addition, kinetic simulations using the Copasi software were employed to determine rate constants for this transformation, implicating facile C-H oxidative addition and slow reductive elimination steps.

  12. An Approach to Mimicking the Sesquiterpene Cyclase Phase by Nickel-Promoted Diene/Alkyne Cooligomerization

    PubMed Central

    Holte, Dane; Götz, Daniel C. G.; Baran, Phil S.

    2012-01-01

    Artificially mimicking the cyclase phase of terpene biosynthesis inspires the invention of new methodologies, since working with carbogenic frameworks containing minimal functionality limits the chemist’s toolbox of synthetic strategies. For example, the construction of terpene skeletons from five-carbon building blocks would be an exciting pathway to mimic in the laboratory. Nature oligomerizes, cyclizes, and then oxidizes γ,γ-dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) to all of the known terpenes. Starting from isoprene, the goal of this work was to mimic Nature’s approach for rapidly building molecular complexity. In principle, the controlled oligomerization of isoprene would drastically simplify the synthesis of terpenes used in the medicine, perfumery, flavor, and materials industries. This article delineates our extensive efforts to cooligomerize isoprene or butadiene with alkynes in a controlled fashion by zero-valent nickel catalysis building off the classic studies by Günther Wilke and coworkers. PMID:22229741

  13. A recyclable and reusable supported Cu(I) catalyzed azide-alkyne click polymerization

    NASA Astrophysics Data System (ADS)

    Wu, Haiqiang; Li, Hongkun; Kwok, Ryan T. K.; Zhao, Engui; Sun, Jing Zhi; Qin, Anjun; Tang, Ben Zhong

    2014-05-01

    The azide-alkyne click polymerization (AACP) has emerged as a powerful tool for the synthesis of functional polytriazoles. While, for the Cu(I)-catalyzed AACP, the removal of the catalytic Cu(I) species from the resulting polytriazoles is difficult, and the research on the recyclability and reusability of the catalyst remains intact. Herein, we reported the first example of using recyclable and reusable supported Cu(I) catalyst of CuI@A-21 for the AACP. CuI@A-21 could not only efficiently catalyze the AACP but also be reused for at least 4 cycles. Moreover, pronounced reduction of copper residues in the products was achieved. Apart from being a green and cost-effective polymer synthesis strategy, this method will also broaden the application of AACP in material and biological sciences and provide guidelines for other polymerizations with metal catalysts.

  14. A recyclable and reusable supported Cu(I) catalyzed azide-alkyne click polymerization

    PubMed Central

    Wu, Haiqiang; Li, Hongkun; Kwok, Ryan T. K.; Zhao, Engui; Sun, Jing Zhi; Qin, Anjun; Tang, Ben Zhong

    2014-01-01

    The azide–alkyne click polymerization (AACP) has emerged as a powerful tool for the synthesis of functional polytriazoles. While, for the Cu(I)-catalyzed AACP, the removal of the catalytic Cu(I) species from the resulting polytriazoles is difficult, and the research on the recyclability and reusability of the catalyst remains intact. Herein, we reported the first example of using recyclable and reusable supported Cu(I) catalyst of CuI@A-21 for the AACP. CuI@A-21 could not only efficiently catalyze the AACP but also be reused for at least 4 cycles. Moreover, pronounced reduction of copper residues in the products was achieved. Apart from being a green and cost-effective polymer synthesis strategy, this method will also broaden the application of AACP in material and biological sciences and provide guidelines for other polymerizations with metal catalysts. PMID:24875854

  15. An approach to mimicking the sesquiterpene cyclase phase by nickel-promoted diene/alkyne cooligomerization.

    PubMed

    Holte, Dane; Götz, Daniel C G; Baran, Phil S

    2012-01-20

    Artificially mimicking the cyclase phase of terpene biosynthesis inspires the invention of new methodologies, since working with carbogenic frameworks containing minimal functionality limits the chemist's toolbox of synthetic strategies. For example, the construction of terpene skeletons from five-carbon building blocks would be an exciting pathway to mimic in the laboratory. Nature oligomerizes, cyclizes, and then oxidizes γ,γ-dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) to all of the known terpenes. Starting from isoprene, the goal of this work was to mimic Nature's approach for rapidly building molecular complexity. In principle, the controlled oligomerization of isoprene would drastically simplify the synthesis of terpenes used in the medicine, perfumery, flavor, and materials industries. This article delineates our extensive efforts to cooligomerize isoprene or butadiene with alkynes in a controlled fashion by zerovalent nickel catalysis building off the classic studies by Wilke and co-workers. PMID:22229741

  16. On the Mechanism of the Digold(I)-Hydroxide-Catalysed Hydrophenoxylation of Alkynes.

    PubMed

    Gómez-Suárez, Adrián; Oonishi, Yoshihiro; Martin, Anthony R; Vummaleti, Sai V C; Nelson, David J; Cordes, David B; Slawin, Alexandra M Z; Cavallo, Luigi; Nolan, Steven P; Poater, Albert

    2016-01-18

    Herein, we present a detailed investigation of the mechanistic aspects of the dual gold-catalysed hydrophenoxylation of alkynes by both experimental and computational methods. The dissociation of [{Au(NHC)}2 (μ-OH)][BF4 ] is essential to enter the catalytic cycle, and this step is favoured by the presence of bulky, non-coordinating counter ions. Moreover, in silico studies confirmed that phenol does not only act as a reactant, but also as a co-catalyst, lowering the energy barriers of several transition states. A gem-diaurated species might form during the reaction, but this lies deep within a potential energy well, and is likely to be an "off-cycle" rather than an "in-cycle" intermediate. PMID:26662656

  17. Gold-alkynyls in catalysis: alkyne activation, gold cumulenes and nuclearity.

    PubMed

    Halliday, Connor J V; Lynam, Jason M

    2016-08-01

    The use of cationic gold(i) species in the activation of substrates containing C[triple bond, length as m-dash]C bonds has become a valuable tool for synthetic chemists. Despite the seemingly simple label of 'alkyne activation', numerous patterns of reactivity and product structure are observed in systems employing related substrates and catalysts. The complications of mechanistic determination are compounded as the number of implicated gold(i) centres involved in catalysis increases and debate about the bonding in proposed intermediates clouds the number and importance of potential reaction pathways. This perspective aims to illustrate some of the principles underpinning gold-alkynyl interactions whilst highlighting some of the contentious areas in the field and offering some insight into other, often ignored, mechanistic possibilities based on recent findings. PMID:27415145

  18. Minimalistic Ditopic Ligands: An α-S,N-Donor-Substituted Alkyne as Effective Intermetallic Conjugation Linker.

    PubMed

    Rüger, Julia; Timmermann, Christopher; Villinger, Alexander; Hinz, Alexander; Hollmann, Dirk; Seidel, Wolfram W

    2016-08-01

    The capability of donor-substituted alkynes to link different metal ions in a side-on carbon donor-chelate coordination mode is extended from the donor centers S and P to the second period element N. The complex [Tp'W(CO)2 {η(2) -C2 (S)(NHBn)}] (Tp'=hydrido-tris(3,5-dimethylpyrazolyl)borate, Bn=benzyl) bearing a terminal sulfur atom and a secondary amine substituent is accessible by a metal-template synthesis. Subsequent deprotonation allowed the formation of remarkably stable heterobimetallic complexes with the [(η(5) -C5 H5 )Ru(PPh3 )] and the [Ir(ppy)2 ] moiety. Electrochemical and spectroscopic investigations (cyclic voltammetry, IR, UV/Vis, luminescence, EPR), as well as DFT calculations, and X-ray structure determinations of the W-Ru complex in two oxidation states reveal a strong metal-metal coupling but also a limited delocalization of excited states. PMID:27272102

  19. Temporal separation of catalytic activities allows anti-Markovnikov reductive functionalization of terminal alkynes

    NASA Astrophysics Data System (ADS)

    Li, Le; Herzon, Seth B.

    2014-01-01

    There is currently great interest in the development of multistep catalytic processes in which one or several catalysts act sequentially to rapidly build complex molecular structures. Many enzymes—often the inspiration for new synthetic transformations—are capable of processing a single substrate through a chain of discrete, mechanistically distinct catalytic steps. Here, we describe an approach to emulate the efficiency of these natural reaction cascades within a synthetic catalyst by the temporal separation of catalytic activities. In this approach, a single catalyst exhibits multiple catalytic activities sequentially, allowing for the efficient processing of a substrate through a cascade pathway. Application of this design strategy has led to the development of a method to effect the anti-Markovnikov (linear-selective) reductive functionalization of terminal alkynes. The strategy of temporal separation may facilitate the development of other efficient synthetic reaction cascades.

  20. Fabrication of carbon nanotube films from alkyne-transition metal complexes

    DOEpatents

    Iyer, Vivekanantan S.; Vollhardt, K. Peter C.

    2007-08-28

    A simple method for the production or synthesis of carbon nanotubes as free-standing films or nanotube mats by the thermal decomposition of transition metal complexed alkynes with aryl, alkyl, alkenyl, or alkynyl substituents. In particular, transition metal (e.g. Co, Ni, Fe, Mo) complexes of diarylacetylenes, e.g. diphenylacetylene, and solid mixtures of these complexes with suitable, additional carbon sources are heated in a vessel. More specifically, the heating of the transition metal complex is completed at a temperature between 400-800.degree. C. and more particularly 550-700.degree. C. for between 0.1 to 24 hours and more particularly 0.5-3 hours in a sealed vessel under a partial pressure of argon or helium.

  1. Facile net cycloaddition approach to optically active 1,5-benzothiazepines.

    PubMed

    Fukata, Yukihiro; Asano, Keisuke; Matsubara, Seijiro

    2015-04-29

    The 1,5-benzothiazepine moiety is well-known as a versatile pharmacophore, and its derivatives are expected to have antagonism against numerous diseases. Thus, it is desirable to develop a synthetic route that enables facile enantioselective preparation of a wide range of such derivatives. Although the cycloaddition approach could be considered a possible route to these compounds, to date, there has been no precedent of such a protocol. We therefore present the first example of a highly enantioselective net [4 + 3] cycloaddition to afford 1,5-benzothiazepines by utilizing α,β-unsaturated acylammonium intermediates generated by chiral isothiourea catalysts, which undergo two sequential chemoselective nucleophilic attacks by 2-aminothiophenols. This protocol provided cycloadducts in extremely high regioselectivity, with a good-to-excellent stereoselectivity being achieved regardless of the steric and electronic properties of the substrates. This method therefore offers promising synthetic routes for the construction of a library of optically active 1,5-benzothiazepines for assay evaluation. PMID:25856510

  2. Acceleration of Enantioselective Cycloadditions Catalyzed by Second-Generation Chiral Oxazaborolidinium Triflimidates by Biscoordinating Lewis Acids.

    PubMed

    Thirupathi, Barla; Breitler, Simon; Mahender Reddy, Karla; Corey, E J

    2016-08-31

    The activation of second-generation fluorinated oxazaborolidines by the strong acid triflimide (Tf2NH) in CH2Cl2 solution leads to highly active chiral Lewis acids that are very effective catalysts for (4 + 2) cycloaddition. We report herein that this catalytic activity can be further enhanced by the use of Tf2NH in combination with the biscoordinating Lewis acid TiCl4 or SnCl4 as a coactivator. The effective increase in acidity of an exceedingly strong protic acid is greater for biscoordinating TiCl4 and SnCl4 than for monocoordinating salts, even the strong Lewis acids AlBr3 and BBr3 in CH2Cl2 or CH2Cl2/toluene. The increase in the effective acidity of Tf2NH can be understood in terms of a stabilized cyclic anionic complex of Tf2N(-) and TiCl4, which implies a broader utility than that described here. The utility of Tf2NH-TiCl4 activation of fluorinated oxazaborolidines is documented by examples including the first enantioselective (4 + 2) cycloaddition to α,β-unsaturated acid chlorides. PMID:27530433

  3. Mono- and multiply-functionalized fullerene derivatives through 1,3-dipolar cycloadditions: A DFT study

    NASA Astrophysics Data System (ADS)

    Anafcheh, Maryam; Ghafouri, Reza

    2014-02-01

    We have performed a computational study to investigate the electronic and chemical properties of mono- and multiply-functionalized fullerene derivatives through the [2+3] cycloaddition reactions of 1,3 dipoles such as nitriloxide (HCåN+-O-), azide (NåN+-NH-) and azomethine ylides (H2C-NH-CH2-) with C60 fullerene. The 1,3-dipolar cycloadditions (1,3 DCs) of one to six dipoles with a C60 molecule are theoretically investigated in terms of geometry, energies, electronic structures, stability and the electrophilicity index. Negative values of reaction energies Er are obtained, which indicate the exothermic character of the adsorption process. Generally, absolute values of Er for the C60/(H2C-NH-CH2-)n compounds are always larger than those of their corresponding compounds C60/(HCåN+-O-)n and C60/(NåN+-NH-)n. The results indicate that the successive 1,3-DC reactions of nitriloxides (HCåN+-O-) and azides (NåN+-NH-), n=1,2, 4 and 6 on the exterior surface of fullerene increases the electrophilicity while the reverse trend is observed for C60/(H2C-NH-CH2-)n. Furthermore, electrophilicity values for the C60/(HCåN+-O-)n and C60/(NåN+-NH-)n compounds are always greater than those of C60.

  4. Low-lying stepwise paths for ethylene 1,3-dipolar cycloadditions: A DFT study

    NASA Astrophysics Data System (ADS)

    Kavitha, K.; Venuvanalingam, P.

    Ethylene reacts with 1,3-dipoles such as diazomethane, nitrile oxide, and nitrone to give a single adduct and the potential energy surfaces of these reactions were completely surveyed with Density Functional Theory at the B3LYP/6-31G(d) level; B3LYP/6-311+G(d,p), QCISD/6-31G(d) level calculations were performed for comparison. These reactions were found to have one concerted and four stepwise paths and all of them were thoroughly examined. Calculations show that anti and syn approaches in the stepwise paths merge at one point in the potential energy surface and the stepwise processes (i.e., through syn transition states) are low-lying and concerted paths that are in close competition with them. A closer examination of the computed barriers of the reactions of ethylene with the above dipoles, cyclopentadiene, 1,3-butadiene, and allyl anion reveals that there is a mechanistic cross-over from concerted to stepwise path. While the neutral cycloaddition partners prefer a concerted path, the charged partners strongly favor a stepwise path. The dipoles have both concerted and stepwise (syn) paths in close competition. Such a mechanistic cross-over has been induced by the polar influence of the charged species and this change-over in mechanism could not be observed with allene cycloadditions with the same set of partners because allene is strongly biased towards the stepwise mechanism.

  5. Revealing Stepwise Mechanisms in Dipolar Cycloaddition Reactions: Computational Study of the Reaction between Nitrones and Isocyanates.

    PubMed

    Darù, Andrea; Roca-López, David; Tejero, Tomás; Merino, Pedro

    2016-01-15

    The mechanism of cycloaddition reactions of nitrones with isocyanates has been studied using density functional theory (DFT) methods at the M06-2X/cc-pVTZ level of theory. The exploration of the potential energy surfaces associated with two reactive channels leading to 1,2,4-oxadiazolidin-5-ones and 1,4,2-dioxazolidines revealed that the cycloaddition reaction takes place through a concerted mechanism in gas phase and in apolar solvents but a stepwise mechanism in polar solvents. In stepwise mechanisms, the first step of the reaction is a rare case in which the nitrone oxygen acts as a nucleophile by attacking the central carbon atom of the isocyanate (interacting with the π-system of the C═O bond) to give an intermediate. The corresponding transition structure is stabilized by an attractive electrostatic interaction favored in a polar medium. The second step of the reaction is the rate-limiting one in which the formation of 1,2,4-oxadiazolidin-5-ones or 1,4,2-dioxazolidines is decided. Calculations indicate that formation of 1,2,4-oxadiazolidin-5-ones is favored both kinetically and thermodynamically independently of the solvent, in agreement with experimental observations. Noncovalent interactions (NCI) and topological analysis of the gradient field of electron localization function (ELF) bonding confirmed the observed interactions. PMID:26682934

  6. Electrochemical impedance spectroscopy sensor for ascorbic acid based on copper(I) catalyzed click chemistry.

    PubMed

    Qiu, Suyan; Gao, Sen; Liu, Qida; Lin, Zhenyu; Qiu, Bin; Chen, Guonan

    2011-07-15

    Copper(I) species can be acquired from the reduction of copper(II) by ascorbic acid (AA) in situ, and which in turn quantitative catalyze the azides and alkynes cycloaddition reaction. In this study, propargyl-functionalized ferrocene (propargyl-functionalized Fc) has been modified on the electrode through reacting with azide terminal modified Au electrode via copper(I) catalyzed azides and alkynes cycloaddition (CuAAC) reaction. The electrochemical impedance spectroscopy (EIS) measurement has been applied to test the electron transfer resistance of the Au electrode before and after click reaction. The changes of the fractional surface coverage (θ) with different AA concentrations are characterized. It is found that the θ value has a linear response to the logarithm of AA concentration in the range of 5.0 pmol/L to 1.0 nmol/L with the detection limits of 2.6 pmol/L. The sensor shows a good stability and selectivity. And it has been successfully applied to the AA detection in the real samples (urine) with satisfactory results. PMID:21596552

  7. Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

    NASA Astrophysics Data System (ADS)

    Sharma, Rishi; Zhang, Issan; Shiao, Tze Chieh; Pavan, Giovanni M.; Maysinger, Dusica; Roy, René

    2016-02-01

    Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications.Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06757j

  8. Pedagogical Comparison of Five Reactions Performed under Microwave Heating in Multi-Mode versus Mono-Mode Ovens: Diels-Alder Cycloaddition, Wittig Salt Formation, E2 Dehydrohalogenation to Form an Alkyne, Williamson Ether Synthesis, and Fischer Esterification

    ERIC Educational Resources Information Center

    Baar, Marsha R.; Gammerdinger, William; Leap, Jennifer; Morales, Erin; Shikora, Jonathan; Weber, Michael H.

    2014-01-01

    Five reactions were rate-accelerated relative to the standard reflux workup in both multi-mode and mono-mode microwave ovens, and the results were compared to determine whether the sequential processing of a mono-mode unit could provide for better lab logistics and pedagogy. Conditions were optimized so that yields matched in both types of…

  9. Intramolecular 1,3-dipolar cycloaddition reactions in the synthesis of complex annelated quinolines, α-carbolines and coumarins.

    PubMed

    Majumder, Swarup; Borah, Pallabi; Bhuyan, Pulak J

    2012-05-01

    In this study, we report the synthesis of several novel dihydroisoxazole-, tetrahydroisoxazole- and dihydropyrazole-fused pyrido[2,3-b]quinolines, α-carbolines, and pyrido[2,3-c]coumarins, respectively, from simple precursors and by exploring intramolecular 1,3-dipolar cycloaddition reactions involving nitrile oxides, nitrones, and nitrile imines as 1,3-dipoles. PMID:22374452

  10. Light-driven nitrile imine-mediated tetrazole-ene cycloaddition as a versatile platform for fullerene conjugation.

    PubMed

    Sugawara, Yuuki; Jasinski, Nils; Kaupp, Michael; Welle, Alexander; Zydziak, Nicolas; Blasco, Eva; Barner-Kowollik, Christopher

    2015-08-21

    An efficient methodology for modular fullerene functionalization via the photo-induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) is introduced. The versatility and platform character of the method is illustrated by the light-driven reaction of fullerenes with small molecule, polymeric and surface-immobilized tetrazoles. The efficient fullerene conjugation is evidenced via mass spectrometric techniques. PMID:26179054

  11. Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ Cycloaddition Reaction: An Experimental Approach.

    PubMed

    Zhong, Di-Chang; Wen, Ya-Qiong; Deng, Ji-Hua; Luo, Xu-Zhong; Gong, Yun-Nan; Lu, Tong-Bu

    2015-09-28

    Using an experimental approach, the role of metal catalysis has been investigated in the in situ cycloaddition reaction of nitrile with azide to form tetrazoles. It has been shown that metal catalysis serves to activate the cyano group in the nitrile reagent by a coordinative interaction. PMID:26293313

  12. Asymmetric azidation-cycloaddition with open-chain peptide-based catalysts. A sequential enantioselective route to triazoles.

    PubMed

    Guerin, David J; Miller, Scott J

    2002-03-13

    A family of beta-substituted histidine-containing peptides has been synthesized to probe the effect of noncovalent conformational rigidification on catalyst enantioselectivity. Unambiguous enhancement of enantioselectivity in the conjugate addition of azide to alpha,beta-unsaturated carboxylate derivatives has been achieved, enabling application to a sequential asymmetric azidation/cycloaddition for the synthesis of optically enriched triazoles and triazolines. PMID:11878965

  13. Catalyst-Controlled Formal [4 + 3] Cycloaddition Applied to the Total Synthesis of (+)-Barekoxide and (−)-Barekol

    PubMed Central

    Lian, Yajing; Miller, Laura C.; Born, Stephen

    2010-01-01

    The tandem cyclopropanation/Cope rearrangement between bicyclic dienes and siloxyvinyldiazoacetate, catalyzed by the dirhodium catalyst Rh2(R-PTAD)4 effectively accomplishes enantiodivergent [4 + 3] cycloadditions. The reaction proceeds by a cyclopropanation followed by a Cope rearrangement of the resulting divinylcyclopropane. This methodology was applied to the synthesis (+)-barekoxide (1) and (−)-barekol (2). PMID:20704267

  14. Photochemical Dimerization of Dibenzylideneacetone: A Convenient Exercise in [2+2] Cycloaddition Using Chemical Ionization Mass Spectrometry

    ERIC Educational Resources Information Center

    Rao, G. Nageswara; Janardhana, Chelli; Ramanathan, V.; Rajesh, T.; Kumar, P. Harish

    2006-01-01

    Chemical reactions induced by light have been utilized for synthesizing highly strained, thermodynamically unstable compounds, which are inaccessible through non-photochemical methods. Photochemical cycloaddition reactions, especially those leading to the formation of four-membered rings, constitute a convenient route to compounds that are…

  15. Facile Synthesis of Stapled, Structurally Reinforced Peptide Helices via A Photoinduced Intramolecular 1,3-Dipolar Cycloaddition Reaction†

    PubMed Central

    Madden, Michael M.; Vera, Claudia I. Rivera; Song, Wenjiao; Lin, Qing

    2009-01-01

    We report the first use of a photoinduced 1,3-dipolar cycloaddition reaction in “stapling” peptide side chains to reinforce a model peptide helical structure with moderate to excellent yields. The resulting pyrazoline “staplers” exhibit unique fluorescence useful in a cell permeability study. PMID:19753366

  16. Microwave-Enhanced Organic Syntheses for the Undergraduate Laboratory: Diels-Alder Cycloaddition, Wittig Reaction, and Williamson Ether Synthesis

    ERIC Educational Resources Information Center

    Baar, Marsha R.; Falcone, Danielle; Gordon, Christopher

    2010-01-01

    Microwave heating enhanced the rate of three reactions typically performed in our undergraduate organic chemistry laboratory: a Diels-Alder cycloaddition, a Wittig salt formation, and a Williamson ether synthesis. Ninety-minute refluxes were shortened to 10 min using a laboratory-grade microwave oven. In addition, yields improved for the Wittig…

  17. Synthesis of (±)-3H-epivincamine via a Rh(II)-Triggered Cyclization/Cycloaddition Cascade

    PubMed Central

    England, Dylan B.

    2008-01-01

    A synthesis of (±)-3H-epivincamine is reported. Important steps include: (1) a Rh(II)-catalyzed intramolecular [3+2]-cycloaddition of an α-diazo indolo amide; (2) a reductive ring opening of the cycloadduct; (3) a decarboethoxylation reaction; and (4) a base-induced keto-amide ring contraction. PMID:17658832

  18. Application of an intramolecular dipolar cycloaddition to an asymmetric synthesis of the fully oxygenated tricyclic core of the stemofoline alkaloids

    PubMed Central

    Carra, Ryan J.; Epperson, Matthew T.; Gin, David Y.

    2008-01-01

    An intramolecular non-stabilized azomethine ylide dipolar cycloaddition was applied toward the first non-racemic synthesis of the fully-oxygenated bridged pyrrolizidine core (45) of (+)-stemofoline (1) in eleven steps from a commercially available starting material. PMID:18443655

  19. Reversal of the Regiochemistry in the Rhodium-Catalyzed [4+3] Cycloaddition Between Vinyldiazoacetates and Dienes

    PubMed Central

    Guzmán, Pablo E.; Lian, Yajing

    2015-01-01

    A regio-, diastereo- and enantioselective [4+3] cycloaddition between vinylcarbenes and dienes has been achieved using the dirhodium tetracarboxylate catalyst Rh2(S-BTPCP)4. This methodology provides facile access to 1,4-cycloheptadienes that are regioisomers of those formed from the tandem cyclopropanation/Cope rearrangement reaction of vinylcarbenes with dienes. PMID:25266984

  20. Metal-Free [2 + 2 + 2] Cycloaddition of Ynamides with Nitriles to Construct 2,4-Diaminopyridines.

    PubMed

    Zhang, Jingyi; Zhang, Qingshuang; Xia, Biao; Wu, Jie; Wang, Xiao-Na; Chang, Junbiao

    2016-07-15

    We present a metal-free [2 + 2 + 2] cycloaddition of ynamides with nitriles that enables highly efficient access to 2,4-diaminopyridines. This catalytic protocol is more environmentally friendly and allows for a concomitant construction of C-C and C-N bonds between ynamides and nitriles, exhibiting excellent chemoselectivity, regioselectivity, and wide functional groups tolerance. PMID:27366955

  1. Metal-Free [2+2+2] Cycloaddition of Ynamides and Nitriles: Mild and Regioselective Synthesis of Fully Substituted Pyridines.

    PubMed

    Wang, Yong; Song, Li-Juan; Zhang, Xinhao; Sun, Jianwei

    2016-08-01

    A metal-free trimolecular [2+2+2] cycloaddition of internal ynamides and nitriles for de novo synthesis of fully substituted pyridines is disclosed. With the versatile Brønsted acid catalyst HNTf2 , the mild intermolecular cyclotrimerization process proceeds with complementary chemoselectivity and excellent regioselectivity. PMID:27381408

  2. Synthesis of 2,3-Disubstituted Benzo[b]furans by the Palladium-Catalyzed Coupling of o-Iodoanisoles and Terminal Alkynes, Followed by Electrophilic Cyclization

    PubMed Central

    Yue, Dawei; Yao, Tuanli; Larock, Richard C.

    2008-01-01

    2,3-Disubstituted benzo[b]furans are readily prepared under very mild reaction conditions by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization using I2, PhSeCl or p-O2NC6H4SCl. Aryl- and vinylic-substituted alkynes undergo electrophilic cyclization in excellent yields. Biologically important furopyridines can be prepared by this approach in high yields. PMID:16323837

  3. Mutual Cooperation in the Formal Allyl Alcohol Nucleophilic Substitution and Hydration of Alkynes for the Construction of γ-Substituted Ketones.

    PubMed

    Huang, Kaimeng; Wang, Hongkai; Liu, Lingyan; Chang, Weixing; Li, Jing

    2016-05-01

    Mutual cooperation in the formal allyl alcohol nucleophilic substitution reaction and hydration of an alkyne has been utilized in the presence of a gold catalyst to give a series of γ-functionalized ketones with high to excellent yields. This reaction actually involved an intramolecular O-H insertion cyclization of an alkyne to form the dihydrofuran intermediate, which was followed by the nucleophilic addition ring-opening of a dihydrofuran to give the target compound. PMID:26946315

  4. Thermal and UV Hydrosilylation of Alcohol-Based Bifunctional Alkynes on Si (111) surfaces: How surface radicals influence surface bond formation

    PubMed Central

    Khung, Y. L.; Ngalim, S. H.; Scaccabarozi, A.; Narducci, D.

    2015-01-01

    Using two different hydrosilylation methods, low temperature thermal and UV initiation, silicon (111) hydrogenated surfaces were functionalized in presence of an OH-terminated alkyne, a CF3-terminated alkyne and a mixed equimolar ratio of the two alkynes. XPS studies revealed that in the absence of premeditated surface radical through low temperature hydrosilylation, the surface grafting proceeded to form a Si-O-C linkage via nucleophilic reaction through the OH group of the alkyne. This led to a small increase in surface roughness as well as an increase in hydrophobicity and this effect was attributed to the surficial etching of silicon to form nanosize pores (~1–3 nm) by residual water/oxygen as a result of changes to surface polarity from the grafting. Furthermore in the radical-free thermal environment, a mix in equimolar of these two short alkynes can achieve a high contact angle of ~102°, comparable to long alkyl chains grafting reported in literature although surface roughness was relatively mild (rms = ~1 nm). On the other hand, UV initiation on silicon totally reversed the chemical linkages to predominantly Si-C without further compromising the surface roughness, highlighting the importance of surface radicals determining the reactivity of the silicon surface to the selected alkynes. PMID:26067470

  5. Thermal and UV Hydrosilylation of Alcohol-Based Bifunctional Alkynes on Si (111) surfaces: How surface radicals influence surface bond formation

    NASA Astrophysics Data System (ADS)

    Khung, Y. L.; Ngalim, S. H.; Scaccabarozi, A.; Narducci, D.

    2015-06-01

    Using two different hydrosilylation methods, low temperature thermal and UV initiation, silicon (111) hydrogenated surfaces were functionalized in presence of an OH-terminated alkyne, a CF3-terminated alkyne and a mixed equimolar ratio of the two alkynes. XPS studies revealed that in the absence of premeditated surface radical through low temperature hydrosilylation, the surface grafting proceeded to form a Si-O-C linkage via nucleophilic reaction through the OH group of the alkyne. This led to a small increase in surface roughness as well as an increase in hydrophobicity and this effect was attributed to the surficial etching of silicon to form nanosize pores (~1-3 nm) by residual water/oxygen as a result of changes to surface polarity from the grafting. Furthermore in the radical-free thermal environment, a mix in equimolar of these two short alkynes can achieve a high contact angle of ~102°, comparable to long alkyl chains grafting reported in literature although surface roughness was relatively mild (rms = ~1 nm). On the other hand, UV initiation on silicon totally reversed the chemical linkages to predominantly Si-C without further compromising the surface roughness, highlighting the importance of surface radicals determining the reactivity of the silicon surface to the selected alkynes.

  6. Calculating the properties of C2H2-C9H16 alkynes, based on the additivity of energy contributions

    NASA Astrophysics Data System (ADS)

    Smolyakov, V. M.; Grebeshkov, V. V.

    2015-05-01

    A ten-constant additive model is obtained for calculating the physicochemical properties of a number of C n H2 n-2 alkynes, based on the group additivity method (with allowance for the initial atomic environment), two topological indices that allow for the second atomic environment, and pairwise non-valence interactions (in implicit form) between three atoms, four atoms, and so forth along the chain of a molecule. Two linear dependences are revealed. The obtained formula is used for numerical calculations of the normal heats of vaporization L NBT and normal boiling temperatures T b of C2H2-C9H16 alkynes, neither of which had been studied experimentally.

  7. Unexpected anion effect in the alkoxylation of alkynes catalyzed by N-heterocyclic carbene (NHC) cationic gold complexes.

    PubMed

    Biasiolo, Luca; Trinchillo, Marina; Belanzoni, Paola; Belpassi, Leonardo; Busico, Vincenzo; Ciancaleoni, Gianluca; D'Amora, Angela; Macchioni, Alceo; Tarantelli, Francesco; Zuccaccia, Daniele

    2014-11-01

    The intermolecular alkoxylation of alkynes is the oldest application of cationic gold(I) catalysts; however, no systematic experimental data about the role of the anion are available. In this contribution, the role of the anion in this catalytic reaction as promoted by a N-heterocyclic carbene-based gold catalyst, [(NHC)AuX] (X=BARF(-) , BF4 (-) , OTf(-) , OTs(-) , TFA(-) , or OAc(-) ) is analyzed, through a combined experimental (NMR spectroscopy) and theoretical (DFT calculation) approach. The most important factor seems to be the ability to abstract the proton from the methanol during the nucleophilic attack, and such ability is related to the anion basicity. On the other hand, too high coordination power or basicity of the anion worsens the catalytic performance by preventing alkyne coordination or by forming too much free methoxide in solution, which poisons the catalyst. The intermediate coordinating power and basicity of the OTs(-) anion provides the best compromise to achieve efficient catalysis. PMID:25263571

  8. Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides.

    PubMed

    Cromm, Philipp M; Schaubach, Sebastian; Spiegel, Jochen; Fürstner, Alois; Grossmann, Tom N; Waldmann, Herbert

    2016-01-01

    Bicyclic peptides are promising scaffolds for the development of inhibitors of biological targets that proved intractable by typical small molecules. So far, access to bioactive bicyclic peptide architectures is limited due to a lack of appropriate orthogonal ring-closing reactions. Here, we report chemically orthogonal ring-closing olefin (RCM) and alkyne metathesis (RCAM), which enable an efficient chemo- and regioselective synthesis of complex bicyclic peptide scaffolds with variable macrocycle geometries. We also demonstrate that the formed alkyne macrocycle can be functionalized subsequently. The orthogonal RCM/RCAM system was successfully used to evolve a monocyclic peptide inhibitor of the small GTPase Rab8 into a bicyclic ligand. This modified peptide shows the highest affinity for an activated Rab GTPase that has been reported so far. The RCM/RCAM-based formation of bicyclic peptides provides novel opportunities for the design of bioactive scaffolds suitable for the modulation of challenging protein targets. PMID:27075966

  9. Synthesis of phenanthrenes through copper-catalyzed cross-coupling of N-tosylhydrazones with terminal alkynes.

    PubMed

    Hossain, Mohammad Lokman; Ye, Fei; Liu, Zhenxing; Xia, Ying; Shi, Yi; Zhou, Lei; Zhang, Yan; Wang, Jianbo

    2014-09-19

    A novel protocol for the synthesis of phenanthrenes through the copper-catalyzed reaction of aromatic tosylhydrazones with terminal alkynes is explored. The reaction proceeds via the formation of an allene intermediate and subsequent six-π-electron cyclization-isomerization, affording phenanthrene derivatives in good yields. The transformation can be performed in two ways: (1) with N-tosylhydrazones derived from [1,1'-biphenyl]-2-carbaldehydes and terminal alkynes as the starting materials and (2) with N-tosylhydrazones derived from aromatic aldehydes and 2-alkynyl biphenyls as the starting materials. This new phenanthrene synthesis uses readily available starting materials and a cheap copper catalyst and has a wide range of functional group compatibility. PMID:25153826

  10. Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides

    PubMed Central

    Cromm, Philipp M.; Schaubach, Sebastian; Spiegel, Jochen; Fürstner, Alois; Grossmann, Tom N.; Waldmann, Herbert

    2016-01-01

    Bicyclic peptides are promising scaffolds for the development of inhibitors of biological targets that proved intractable by typical small molecules. So far, access to bioactive bicyclic peptide architectures is limited due to a lack of appropriate orthogonal ring-closing reactions. Here, we report chemically orthogonal ring-closing olefin (RCM) and alkyne metathesis (RCAM), which enable an efficient chemo- and regioselective synthesis of complex bicyclic peptide scaffolds with variable macrocycle geometries. We also demonstrate that the formed alkyne macrocycle can be functionalized subsequently. The orthogonal RCM/RCAM system was successfully used to evolve a monocyclic peptide inhibitor of the small GTPase Rab8 into a bicyclic ligand. This modified peptide shows the highest affinity for an activated Rab GTPase that has been reported so far. The RCM/RCAM-based formation of bicyclic peptides provides novel opportunities for the design of bioactive scaffolds suitable for the modulation of challenging protein targets. PMID:27075966

  11. Identification of a Grain Beetle Macrolide Pheromone and Its Synthesis by Ring-Closing Metathesis Using a Terminal Alkyne.

    PubMed

    Hötling, Susann; Bittner, Celine; Tamm, Matthias; Dähn, Sonja; Collatz, Jana; Steidle, Johannes L M; Schulz, Stefan

    2015-10-16

    A major C18-macrolide was found during analysis of the frass of the storage beetle Oryzaephilus surinamensis to be (9Z,12Z,15R)-octadeca-9,12-dien-15-olide (10, cucujolide XI). The synthesis used ring-closing alkyne metathesis as a key step. The highly active 2,4,6-trimethylbenzylidyne molybdenum complex [MesCMo{OC(CF3)2Me}3] (12) allowed the use of a terminal alkyne and afforded the product in excellent yield. Bioassays proved the activity of the R-enantiomer 10 in the aggregation of the beetle. Cucujolide XI is the first macrolide pheromone oxidized at the ω-4 position. PMID:26406161

  12. Catalytic Enantioselective Conjugate Alkynylation of α,β-Unsaturated 1,1,1-Trifluoromethyl Ketones with Terminal Alkynes.

    PubMed

    Sanz-Marco, Amparo; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R

    2016-07-11

    The first catalytic enantioselective conjugate alkynylation of α,β-unsaturated 1,1,1-trifluoromethyl ketones has been carried out. Terminal alkynes and 1,3-diynes were treated with trifluoromethyl ketones in the presence of a low catalytic load of a Cu(I) -MeOBIPHEP complex (2.5 mol %) and triethylamine (10 mol %) to give the corresponding trifluoromethyl ketones bearing a propargylic stereogenic center at the β position with good yields and excellent enantiomeric excesses in most of the cases. No 1,2-addition products were formed under the reaction conditions. The procedure showed broad substrate scope for alkyne, diyne, and enone. A rationale for the observed stereochemistry has been provided. Finally, the potential application of the reaction products in the synthesis of chiral tetrahydrofurans bearing a trifluoromethylated quaternary stereocenter has been devised. PMID:27334465

  13. Palladium-Catalyzed Dearomative Allylic Alkylation of Indoles with Alkynes To Synthesize Indolenines with C3-Quarternary Centers.

    PubMed

    Gao, Shang; Wu, Zijun; Fang, Xinxin; Lin, Aijun; Yao, Hequan

    2016-08-01

    A palladium-catalyzed dearomative allylic alkylation of indoles with alkynes to construct indolenines with C3-quarternary centers was reported. The in situ formed arylallene intermediate omitted the need to install leaving groups on the allylic compounds and employ extra oxidants to oxidize the allylic C-H bonds. The reaction exhibited good functional group tolerance and high atom economy. Moreover, the reaction was further expanded to synthesize pyrroloindolines and furanoindolines. PMID:27442021

  14. Enantioselective Synthesis of 3-Alkynyl-3-hydroxyindolin-2-ones by Copper-Catalyzed Asymmetric Addition of Terminal Alkynes to Isatins.

    PubMed

    Xu, Ning; Gu, Da-Wei; Zi, Jing; Wu, Xin-Yan; Guo, Xun-Xiang

    2016-05-20

    A highly efficient copper-catalyzed asymmetric addition of terminal alkynes to isatins has been developed. In the presence of a catalytic amount of copper iodide and a chiral phosphine ligand, the reaction gave the corresponding chiral 3-alkynyl-3-hydroxyindolin-2-ones in high yields with high enantioselectivity. This methodology has a broad substrate scope, and the synthetic utility of the present protocol was further demonstrated by the transformation of chiral alkynylation products. PMID:27152462

  15. Odorless, One-Pot Regio- and Stereoselective Iodothiolation of Alkynes with Sodium Arenesulfinates under Metal-Free Conditions in Water.

    PubMed

    Lin, Ya-mei; Lu, Guo-ping; Cai, Chun; Yi, Wen-bin

    2015-07-01

    A newly developed regio- and stereoselective radical addition of alkyne under metal-free conidtions has been disclosed. This chemistry, in which odorless sodium arenesulfinates in place of thiols are used as the sulfur reagent, provides an efficient, one-pot approach for the generation of β-iodoalkenyl sulfides, which can be easily further functionalized to derive various alkenes and alkynyl sulfides rendering this methodology attractive to both synthetic and medicinal chemistry. PMID:26084011

  16. Gold-catalyzed oxidative cross-coupling of terminal alkynes: selective synthesis of unsymmetrical 1,3-diynes.

    PubMed

    Peng, Haihui; Xi, Yumeng; Ronaghi, Nima; Dong, Boliang; Akhmedov, Novruz G; Shi, Xiaodong

    2014-09-24

    Gold-catalyzed oxidative cross-coupling of alkynes to unsymmetrical diynes has been achieved for the first time. A N,N-ligand (1,10-Phen) and PhI(OAc)2 were identified as crucial factors to promote this transformation, giving the desired cross-coupled conjugated diynes in excellent heteroselectivity (>10:1), in good to excellent yields, and with large substrate tolerability. PMID:25184690

  17. Modular Attachment of Appended Boron Lewis Acids to a Ruthenium Pincer Catalyst: Metal-Ligand Cooperativity Enables Selective Alkyne Hydrogenation.

    PubMed

    Tseng, Kuei-Nin T; Kampf, Jeff W; Szymczak, Nathaniel K

    2016-08-24

    A new series of bifunctional Ru complexes with pendent Lewis acidic boranes were prepared by late-stage modification of an active hydrogen-transfer catalyst. The appended boranes modulate the reactivity of a metal hydride as well as catalytic hydrogenations. After installing acidic auxiliary groups, the complexes become multifunctional and catalyze the cis-selective hydrogenation of alkynes with higher rates, conversions, and selectivities compared with the unmodified catalyst. PMID:27472301

  18. Rhodium-catalyzed annulative coupling of 3-phenylthiophenes with alkynes involving double C-H bond cleavages.

    PubMed

    Iitsuka, Tomonori; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro

    2014-01-01

    Double CH bond activation took place efficiently upon treatment of 3-phenylthiophenes with alkynes in the presence of a rhodium catalyst and a copper salt oxidant to form the corresponding naphthothiophene derivatives. Dehydrogenative coupling with alkenes was also found to occur on the phenyl moiety rather than the thiophene ring. These reactions provide straightforward synthetic methods for π-conjugated molecules involving a thiophene unit from readily available, simple building blocks. PMID:24288235

  19. Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N-Aryl Glycine Esters with Terminal Alkynes.

    PubMed

    Xie, Zhiyu; Liu, Xigong; Liu, Lei

    2016-06-17

    A copper-catalyzed enantioselective cross-coupling of a Csp3-H moiety (N-aryl glycine ester) with a Csp-H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural α-amino acids. PMID:27269737

  20. Chemical Amination via Cycloaddition of Graphene for Use in a Glucose Sensor.

    PubMed

    Qin, Hongyi; Hwang, Taehyun; Ahn, Chisung; Kim, Jang Ah; Jin, Yinhua; Cho, Yujin; Shin, Cheolmin; Kim, Taesung

    2016-05-01

    Graphene was chemically aminated via cycloaddition. Aziridine-ring linkages were formed by covalently modifying the C-C double bonds in graphene. The aminated graphene presents an enhanced hydrophilicity, the contact angle with water decreases from 80.5 degrees to 58.5 degrees. And the conductivity of aminated graphene exhibits exponential decay as the reaction time increase. If the reaction time is 90 min, the resistance of aminated graphene was increased from -32 Ω to -2744 Ω. Because the amino group has good biocompatibility, the aminated graphene is designed for use as an enzyme sensor platform, such as glucose sensor based on glucose oxidase. The aminated graphene exhibited a good detection response for glucose. The increase in device current is about 12% in 1.2 mg/mL glucose solution. PMID:27483866