Sample records for ylide cycloaddition methodology

  1. Stereocontrolled syntheses of the nemorensic acids using 6-diazoheptane-2,5-dione in carbonyl ylide cycloadditions.

    PubMed

    Hodgson, David M; Le Strat, Frédéric; Avery, Thomas D; Donohue, Andrew C; Brückl, Tobias

    2004-12-10

    Levulinic acid-derived 6-diazoheptane-2,5-dione (9) serves as a common precursor in a formal synthesis of frontalin 19, and in syntheses of cis-nemorensic acid 1, 4-hydroxy-cis-nemorensic acid 2, 3-hydroxy-cis-nemorensic acid 3, and nemorensic acid 4. The key step in these syntheses is the Rh(2)(OAc)(4)-catalyzed tandem carbonyl ylide formation-intermolecular 1,3-dipolar cycloadditions of diazodione 9 with formaldehyde, alkynes or allene, which occur with high regioselectivity. Subsequent oxidative cleavage of the ring originally derived from the cyclic carbonyl ylide intermediate provides a straightforward access to polysubstituted tetrahydrofurans, and in particular an efficient entry to the nemorensic acids. Enantioselective cycloadditions with diazodione 9, using chiral rhodium catalysts, gave cycloadducts in up to 51% ee.

  2. Intramolecular Hydrogen Bond Activation: Thiourea-Organocatalyzed Enantioselective 1,3-Dipolar Cycloaddition of Salicylaldehyde-Derived Azomethine Ylides with Nitroalkenes.

    PubMed

    Esteban, Francisco; Cieślik, Wioleta; Arpa, Enrique M; Guerrero-Corella, Andrea; Díaz-Tendero, Sergio; Perles, Josefina; Fernández-Salas, José A; Fraile, Alberto; Alemán, José

    2018-03-02

    An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o -hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceed.

  3. Influence of Endo- and Exocyclic Heteroatoms on Stabilities and 1,3-Dipolar Cycloaddition Reactivities of Mesoionic Azomethine Ylides and Imines.

    PubMed

    Champagne, Pier Alexandre; Houk, K N

    2017-10-20

    The geometries, stabilities, and 1,3-dipolar cycloaddition reactivities of 24 mesoionic azomethine ylides and imines were investigated using density functional theory calculations at the M06-2X/6-311+G-(d,p)/M06-2X/6-31G-(d) level. The computed structures highlight how the commonly used "aromatic" resonance form should be replaced by two more accurate resonance structures. Stabilities of the dipoles were assessed by various homodesmotic schemes and are consistent with these compounds being nonaromatic. The activation free energies with ethylene or acetylene range from 11.8 to 36.6 kcal/mol. Within each dipole type, the predicted cycloaddition reactivities correlate with the reaction energies and the resonance stabilization energies provided by the various substituents. Endocyclic (X) heteroatoms increase the reactivity of the 1,3-dipoles in the order of O > NH ≅ S, whereas exocyclic (Y) substituents increase it in the order of CH 2 > NH > O > S. Distortion/interaction analysis indicated that the difference in reactivity between differently substituted 1,3-dipoles is driven by distortion, whereas the difference between azomethine ylides and imines is related to lower interaction energies of imines with the dipolarophiles.

  4. A new entry to azomethine ylides from allylic amines and glyoxals: shifting the reliance on amino ester precursors.

    PubMed

    Machamer, Natalie K; Liu, Xiaoxi; Waters, Stephen P

    2014-10-03

    The first examples of azomethine ylides derived from allylic amine and glyoxal precursors are reported. The condensation of primary allylic and α-aryl amines with glyoxylates or α-aryl glyoxals affords conjugated azomethine ylides that undergo facile [3 + 2] cycloaddition, providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessed through the classical use of amino esters as ylide precursors.

  5. Stereo-, Regio-, and Chemoselective [3 + 2]-Cycloaddition of (2E,4E)-Ethyl 5-(Phenylsulfonyl)penta-2,4-dienoate with Various Azomethine Ylides, Nitrones, and Nitrile Oxides: Synthesis of Pyrrolidine, Isoxazolidine, and Isoxazoline Derivatives and a Computational Study.

    PubMed

    Sankar, Ulaganathan; Surya Kumar, Ch Venkata; Subramanian, V; Balasubramanian, K K; Mahalakshimi, S

    2016-03-18

    One-pot chemo-, regio-, and stereoselective synthesis of series of heterocyclic and spiroheterocyclic compounds was accomplished through mono- and bis[3 + 2]-cycloaddition reactions of (2E,4E)-ethyl 5-(phenylsulfonyl)penta-2,4-dienoate as a dipolarophile with azomethine ylides, nitrones, and nitrile oxides in good yields. The structures of the products were established by spectroscopic techniques as well as by single-crystal XRD study, and DFT calculations were performed to further understand the mechanism of this [3 + 2]-cycloaddition reaction.

  6. Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds.

    PubMed

    Day, Jonathan; McKeever-Abbas, Ben; Dowden, James

    2016-05-04

    Commercially available iron(III) and copper(I) complexes catalyzed multicomponent cycloaddition reactions between diazo compounds, pyridines, and electrophilic alkenes to give alkaloid-inspired tetrahydroindolizidines in high yield with high diastereoselectivity. Hitherto, the catalytic formation of versatile pyridinium ylides from metal carbenes has been poorly developed; the broad utility demonstrated herein sets the stage for the invention of further multicomponent reactions in future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Chemistry of withaferin-A: chemo, regio, and stereoselective synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A via one-pot three-component [3+2] azomethine ylide cycloaddition and their cytotoxicity evaluation.

    PubMed

    Bharitkar, Yogesh P; Kanhar, Satish; Suneel, Neradibilli; Mondal, Susanta Kumar; Hazra, Abhijit; Mondal, Nirup B

    2015-05-01

    Withaferin-A (WA) has attracted the attention of chemists as well as biologists due to its interesting structure and various bio-activities. In light of the promising biological importance of WA as well as pyrrolidine-2-spiro-3'-oxindole ring system, we became interested in the synthesis of a combined motif involving both the ring systems via the 1,3-dipolar cycloaddition of WA at Δ(2)-bond of the α,β-unsaturated carbonyl system. We now report a facile, atom-economic synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A (10 compounds) via the intermolecular cycloaddition of azomethine ylides generated in situ from proline and isatins/acenaphthoquinone. The reaction is highly chemo, regio, and stereoselective affording the cis-fused products with β-orienting hydrogen. The structures were determined by 1D/2D NMR spectroscopic data analysis and unequivocally confirmed by X-ray crystallographic analysis in some cases. Bioevaluation of the compounds against six cancer lines (e.g., CHO, HepG2, HeLa, HEK 293, MDCK-II, and Caco-2) identified 4 promising potential anticancer compounds.

  8. Aromatic C=C bonds as dipolarophiles: facile reactions of uncomplexed electron-deficient benzene derivatives and other aromatic rings with a non-stabilized azomethine ylide.

    PubMed

    Lee, Sunyoung; Diab, Sonia; Queval, Pierre; Sebban, Muriel; Chataigner, Isabelle; Piettre, Serge R

    2013-05-27

    Non-stabilized azomethine ylide 4a reacts smoothly at room temperature with a variety of uncomplexed aromatic heterocycles and carbocycles on the condition that the ring contains at least one or two electron-withdrawing substituents, respectively. Aromatic substrates, including pyridine and benzene derivatives, participate as 2π components in [3+2] cycloaddition reactions and interact with one, two, or three equivalent(s) of the ylide, depending on their structure and substitution pattern. Thus, this process affords highly functionalized polycyclic structures that contain between one and three pyrrolidinyl ring(s) in useful yields. These results indicate that the site selectivity of the cycloaddition reactions strongly depends on both the nature and the positions of the substituents. In most cases, the second 1,3-dipolar reaction occurs on the opposite face to the one that contains the first pyrrolidinyl ring. DFT calculations on model compounds indicate that a concerted mechanism features a low activation barrier. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. The Rhodium(II) Carbenoid Cyclization-Cycloaddition Cascade of α-Diazo Dihydroindolinones for the Synthesis of Novel Azapolycyclic Ring Systems‡

    PubMed Central

    England, Dylan B.; Eagan, James M.; Merey, Gokce; Anac, Olcay; Padwa, Albert

    2008-01-01

    Tandem carbonyl ylide formation-1,3-dipolar cycloaddition of α-diazo N-acetyl-tetrahydro-β-carbolin-1-one derivatives occur efficiently in the presence of a dirhodium catalyst to afford bimolecular cycloadducts in high yield. The Rh(II)-catalyzed reaction also takes place intramolecularly to give products derived from trapping of the carbonyl ylide dipole with a tethered alkene. The power of the intramolecular cascade sequence is that it rapidly assembles a pentacyclic ring system containing three new stereocenters and two adjacent quaternary centers stereospecifically in a single step and in high yield. PMID:18437248

  10. A Facile One-Pot Construction of Succinimide-Fused Spiro[Pyrrolidine-2,3'-Oxindoles] via 1,3-Dipolar Cycloaddition Involving 3-Amino Oxindoles and Maleimides.

    PubMed

    Jin, Lunqiang; Liang, Feng

    2018-03-05

    Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3'-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with maleimides has been described. The protocol provides a facile and efficient access to structurally diverse succinimide-fused spiro[pyrrolidine-2,3'-oxindole] compounds in good to high yields (up to 93%) with moderate to excellent diastereoselectivities (up to >95:5). The relative stereochemistry of cycloaddition products has been assigned by X-ray diffraction analysis.

  11. Rhodium(II)-catalyzed enantioselective synthesis of troponoids.

    PubMed

    Murarka, Sandip; Jia, Zhi-Jun; Merten, Christian; Daniliuc, Constantin-G; Antonchick, Andrey P; Waldmann, Herbert

    2015-06-22

    We report a rhodium(II)-catalyzed highly enantioselective 1,3-dipolar cycloaddition reaction between the carbonyl moiety of tropone and carbonyl ylides to afford troponoids in good to high yields with excellent enantioselectivity. We demonstrate that α-diazoketone-derived carbonyl ylides, in contrast to carbonyl ylides derived from diazodiketoesters, undergo [6+3] cycloaddition reactions with tropone to yield the corresponding bridged heterocycles with excellent stereoselectivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Bonding properties and bond activation of ylides: recent findings and outlook.

    PubMed

    Urriolabeitia, Esteban P

    2008-11-14

    The interaction of phosphorus and nitrogen ylides with metallic precursors has been examined from different points of view. The first one is related to the bonding properties of the ylides. Ylides with a unique stabilizing group bond through different atoms (the Calpha or the heteroatoms); while ylides with two stabilizing groups never coordinate through the Calpha atom. In the second section we examine the cause of the stereoselective coordination of bisylides of phosphorus, nitrogen and arsenic, and of mixed bisylides. We describe here the very interesting conformational preferences found in these systems, which have been determined and characterized. The DFT study of these bisylides has allowed for the characterization of strong intramolecular PO and AsO interactions, as well as moderate CHO[double bond, length as m-dash]C hydrogen bonds as the source of these conformational preferences. The third topic is related to the amazing reactivity of phosphorus ylides in bond activation processes. Depending on the nature of the metallic precursors, ylides can behave as sources of carbenes, of phosphine derivatives, of other ylides or of orthometallated complexes through P[double bond, length as m-dash]C, P-C or C-H bond activation reactions.

  13. 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

  14. An ylide transformation of rhodium(I) carbene: enantioselective three-component reaction through trapping of rhodium(I)-associated ammonium ylides by β-nitroacrylates.

    PubMed

    Ma, Xiaochu; Jiang, Jun; Lv, Siying; Yao, Wenfeng; Yang, Yang; Liu, Shunying; Xia, Fei; Hu, Wenhao

    2014-11-24

    The chiral Rh(I)-diene-catalyzed asymmetric three-component reaction of aryldiazoacetates, aromatic amines, and β-nitroacrylates was achieved to obtain γ-nitro-α-amino-succinates in good yields and with high diastereo- and enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of Rh(I)-associated ammonium ylides by nitroacrylates. This new transformation represents the first example of Rh(I)-carbene-induced ylide transformation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Cross-Coupling of α-Carbonyl Sulfoxonium Ylides with C-H Bonds.

    PubMed

    Barday, Manuel; Janot, Christopher; Halcovitch, Nathan R; Muir, James; Aïssa, Christophe

    2017-10-09

    The functionalization of carbon-hydrogen bonds in non-nucleophilic substrates using α-carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross-coupling reactions of sulfoxonium ylides with C(sp 2 )-H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C-H activation, migratory insertion of the ylide into the carbon-metal bond, and protodemetalation, the last step being turnover-limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium-catalyzed dehydrative cyclization. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

    PubMed Central

    Mereshchenko, Andrey S; Ivanov, Alexey V; Baranovskii, Viktor I; Rodina, Ludmila L

    2015-01-01

    Summary The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C=S ylides bearing at least one acyl group is identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes followed by their spontaneous desulfurization yielding the corresponding alkenes. Finally, carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first stage of the cycloaddition process. PMID:25977725

  17. A combined experimental and theoretical study of the thermal [3+2] cycloaddition of carbonyl ylides with activated alkenes

    NASA Astrophysics Data System (ADS)

    Hamza-Reguig, Samira; Bentabed-Ababsa, Ghenia; Domingo, Luis R.; Ríos-Gutiérrez, Mar; Philippot, Stéphanie; Fontanay, Stéphane; Duval, Raphaël E.; Ruchaud, Sandrine; Bach, Stéphane; Roisnel, Thierry; Mongin, Florence

    2018-04-01

    4-Benzoyl-3,5-diaryltetrahydrofuran-2,2-dicarbonitriles were first synthesized from 2,2-dicyano-3-aryloxiranes and chalcones at toluene reflux; the 4,5-cis products proved to be predominantly formed and were isolated. Whereas shortened reaction times were observed by using microwave irradiation or catalytic cuprous chloride, no significant stereoselectivity change was in general noticed. Reacting 2,2-dicyano-3-aryloxiranes with 2-cyclopentenone next afforded 3-aryl-4-oxohexahydro-1H-cyclopenta[c]furan-1,1-dicarbonitriles, and the endo stereoisomers were isolated. That no stereoselectivity change was noticed in the presence of cuprous chloride rather suggests an impact of the salt on the epoxide ring opening. Finally, treatment of 2,2-dicyano-3-aryloxiranes by 2-morpholinoacrylonitrile yielded 3-cyano-3-morpholino-5-phenyltetrahydrofuran-2,2-dicarbonitriles from which the preponderant trans isomers were isolated. Importantly, the molecular mechanism of the domino reaction between 2,2-dicyano-3-phenyloxirane and 2-cyclopentenone was studied. The rate-determining thermal ring opening of the oxirane is followed by a non-concerted pseudoradical-type reaction of the carbonyl ylide with 2-cyclopentenone. Using the bond evolution theory also allowed the regioselectivity of this non-polar reaction to be explained.

  18. The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

    PubMed Central

    2016-01-01

    Conspectus Redox-neutral methods for the functionalization of amine α-C–H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C–H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet–Spengler, and Kabachnik–Fields reactions, Friedel–Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C–H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic

  19. The azomethine ylide route to amine C-H functionalization: redox-versions of classic reactions and a pathway to new transformations.

    PubMed

    Seidel, Daniel

    2015-02-17

    Conspectus Redox-neutral methods for the functionalization of amine α-C-H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C-H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel-Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C-H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been

  20. Experimental and computational study of the bonding properties of mixed bis-ylides of phosphorus and sulfur.

    PubMed

    Serrano, Elena; Navarro, Rafael; Soler, Tatiana; Carbó, Jorge J; Lledós, Agustí; Urriolabeitia, Esteban P

    2009-07-20

    The reactivity of the known ylide-sulfonium salt [Ph(3)P=CHC(O)CH(2)SMe(2)]Br 1 and the new ylide-sulfide [Ph(3)P=CHC-(O)CH(2)SMe] 2 toward Pd(II) complexes has been studied. Compound 1 reacts with PdCl(2)(NCMe)(2) and NEt(3) to give cis-[PdCl(2)[Ph(3)PCHC(O)CHSMe(2)-kappa-C,C

  1. Ylide Ligands as Building Blocks for Bioactive Group 11 Metal Complexes.

    PubMed

    Gimeno, M Concepción; Johnson, Alice; Marzo, Isabel

    2018-05-22

    The reactivity of the phosphonium salt, (cyanomethyl)triphenylphosphonium chloride, and the ylide, triphenylphosphoniumcyanomethylide, towards group eleven metal complexes is described. Mononuclear neutral gold(I) and gold(III) complexes of the type [AuX{CH(CN)PPh3}] or [AuX3{CH(CN)PPh3}], and cationic derivatives such as [AuL{CH(CN)PPh3}]X have been prepared. Surprisingly the cationic gold species could only be prepared with ligands with a large steric hindrance such as bulky NHCs or the JohnPhos phosphine, in contrast with silver and copper derivatives which have dimeric structures with coordination to the cyano group of the ylide. Bis(ylide)metal complexes have been synthesised in which a different structure is observed for gold compared to copper and silver. While gold shows mononuclear species, the silver complex presents a bidimensional polymeric structure as a result of further coordination of the silver centre to the nitrogen of the cyano group. These complexes possess two chiral centres and the gold compound is obtained as a mixture of diastereoisomers, whereas the copper and silver derivatives afford only one diastereroisomer. These compounds were screened for the in vitro cytotoxic activity against the human lung carcinoma cell line (A549). The IC50 values reveal an excellent cytotoxic activity for these metal complexes compared with cisplatin. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Pressure-accelerated azide-alkyne cycloaddition: micro capillary versus autoclave reactor performance.

    PubMed

    Borukhova, Svetlana; Seeger, Andreas D; Noël, Timothy; Wang, Qi; Busch, Markus; Hessel, Volker

    2015-02-01

    Pressure effects on regioselectivity and yield of cycloaddition reactions have been shown to exist. Nevertheless, high pressure synthetic applications with subsequent benefits in the production of natural products are limited by the general availability of the equipment. In addition, the virtues and limitations of microflow equipment under standard conditions are well established. Herein, we apply novel-process-window (NPWs) principles, such as intensification of intrinsic kinetics of a reaction using high temperature, pressure, and concentration, on azide-alkyne cycloaddition towards synthesis of Rufinamide precursor. We applied three main activation methods (i.e., uncatalyzed batch, uncatalyzed flow, and catalyzed flow) on uncatalyzed and catalyzed azide-alkyne cycloaddition. We compare the performance of two reactors, a specialized autoclave batch reactor for high-pressure operation up to 1800 bar and a capillary flow reactor (up to 400 bar). A differentiated and comprehensive picture is given for the two reactors and the three methods of activation. Reaction speedup and consequent increases in space-time yields is achieved, while the process window for favorable operation to selectively produce Rufinamide precursor in good yields is widened. The best conditions thus determined are applied to several azide-alkyne cycloadditions to widen the scope of the presented methodology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Pd(II) and Pt(II) complexes of α-keto stabilized sulfur ylide: Synthesis, structural, theoretical and catalytic activity studies

    NASA Astrophysics Data System (ADS)

    Sabounchei, Seyyed Javad; Hashemi, Ali; Sedghi, Asieh; Bayat, Mehdi; Akhlaghi Bagherjeri, Fateme; Gable, Robert W.

    2017-05-01

    Reaction of dimethyl sulfide with 2, 3‧-dibromoacetophenone led to formation of sulfonium salt [Me2SCH2C(O)C6H4-m-Br]Br (1). The resulted sulfonium salt was treated with NaOH and gave the α-keto stabilized sulfur ylide Me2SC(H)C(O)C6H4-m-Br (2). This ligand was reacted with [MCl2(cod)] (M = Pd, Pt; cod = 1,5-cyclooctadiene) to form the new cis- and trans-[MCl2(ylide)2] (M = Pd (cis- and trans-3), Pt (cis- and trans-4)) complexes. Characterization of the obtained compounds was performed by elemental analysis, IR, 1H and 13C NMR. Recrystallization of dichlorobis(ylide) palladium(II) and platinum(II) complexes from DMSO solution yielded the crystalline products, which X-ray diffraction data revealed that the both compounds were crystallized as cis-[MCl2(ylide)(DMSO)] (M = Pd (5), Pt (6)) complexes. Also, a theoretical study on structure and nature of the Msbnd C bonding between the Y ligand (ylide) and [MCl2·DMSO] fragments in [YMCl2·DMSO] (M = Pd, Pt) complexes has been reported via NBO and energy-decomposition analysis (EDA). Furthermore, the palladium catalyzed Suzuki-Miyaura reaction of various aryl chlorides with arylboronic acids was performed. The results showed that the Pd(II) complexes cis- and trans-3 catalyzed efficiently coupling reactions at low catalyst loading and short reaction time.

  4. Switchable regioselectivity in amine-catalysed asymmetric cycloadditions

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi; Wang, Zhou-Xiang; Zhou, Yuan-Chun; Xiao, Wei; Ouyang, Qin; Du, Wei; Chen, Ying-Chun

    2017-06-01

    Building small-molecule libraries with structural and stereogenic diversity plays an important role in drug discovery. The development of switchable intermolecular cycloaddition reactions from identical substrates in different regioselective fashions would provide an attractive protocol. However, this also represents a challenge in organic chemistry, because it is difficult to control regioselectivity to afford the products exclusively and at the same time achieve high levels of stereoselectivity. Here, we report the diversified cycloadditions of α‧-alkylidene-2-cyclopentenones catalysed by cinchona-derived primary amines. An asymmetric γ,β‧-regioselective intermolecular [6+2] cycloaddition reaction with 3-olefinic (7-aza)oxindoles is realized through the in situ generation of formal 4-aminofulvenes, while a different β,γ-regioselective [2+2] cycloaddition reaction with maleimides to access fused cyclobutanes is disclosed. In contrast, an intriguing α,γ-regioselective [4+2] cycloaddition reaction is uncovered with the same set of substrates, by employing an unprecedented dual small-molecule catalysis of amines and thiols. All of the cycloaddition reactions exhibit excellent regio- and stereoselectivity, producing a broad spectrum of chiral architectures with high structural diversity and molecular complexity.

  5. Exceptionally Strong Electron-Donating Ability of Bora-Ylide Substituent vis-à-vis Silylene and Silylium Ion.

    PubMed

    Rosas-Sánchez, Alfredo; Alvarado-Beltran, Isabel; Baceiredo, Antoine; Saffon-Merceron, Nathalie; Massou, Stéphane; Branchadell, Vicenç; Kato, Tsuyoshi

    2017-08-21

    Electropositive boron-based substituent (phosphonium bora-ylide) with an exceptionally strong π- and σ-electron donating character dramatically increases the stability of a new type of N-heterocyclic silylene 2 featuring amino- and bora-ylide-substituents. Moreover, the related silylium ion 4 and transition-metal-silylene complexes, with trigonal-planar geometries around the silicon center, are also well stabilized. Therefore, the N,B-heterocyclic silylene 2 can be used as a strongly electron-donating innocent ligand in coordination chemistry similarly to N-heterocyclic carbenes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Solvent-free mechanochemical preparation of phosphonium salts, phosphorus ylides, and olefins

    DOEpatents

    Pecharsky, Vitalij K.; Balema, Viktor P.; Wiench, Jerzy W.; Pruski, Marek

    2004-05-04

    The present invention provides a method of preparing a phosphonium salt of the formula [R.sup.1 R.sup.2 R.sup.3 P--CR.sup.4 R.sup.5 R.sup.6 ]X, comprising ball-milling a phosphine of the formula R.sup.1 R.sup.2 R.sup.3 P with a compound of the formula XCR.sup.4 R.sup.5 R.sup.6 ; a method of preparing a phosphorus ylide of the formula R.sup.1 R.sup.2 R.sup.3 P.dbd.CR.sup.4 R.sup.5, comprising ball-milling a phosphonium salt of the formula [R.sup.1 R.sup.2 R.sup.3 P--HCR.sup.4 R.sup.5 ]X in the presence of a base; and a method of preparing an olefin of the formula R.sup.4 R.sup.5 C.dbd.CR.sup.7 H or R.sup.4 R.sup.5 C.dbd.CR.sup.7 R.sup.8, comprising ball-milling a phosphorus ylide of the formula R.sup.1 R.sup.2 R.sup.3 P.dbd.CR.sup.4 R.sup.5 with a compound of the formula R.sup.7 C(O)H or R.sup.7 C(O)R.sup.8. The inventive method produces phosphonium salts and phosphorus ylides by mechanical processing solid reagents under solvent-free conditions. The advantages of the present invention over conventional solution methods, include: (1) extremely high selectivity; (2) high yields; (3) low processing temperatures; (4) simple and scalable reactions using commercially available equipment; and (5) the complete elimination of solvents from the reaction.

  7. Brucine diol-copper-catalyzed asymmetric synthesis of endo-pyrrolidines: the mechanistic dichotomy of imino esters.

    PubMed

    Li, Jian-Yuan; Kim, Hun Young; Oh, Kyungsoo

    2015-03-06

    Enantio- and diastereodivergent approaches to pyrrolidines are described by using catalyst- and substrate-controlled reaction pathways. A concerted endo-selective [3 + 2]-cycloaddition pathway is developed for the reaction of methyl imino ester, whereas endo-pyrrolidines with an opposite absolute stereochemical outcome are prepared by using the stepwise reaction pathway of tert-butyl imino ester. The development of catalyst- and substrate-controlled stereodivergent approaches highlights the inherent substrate-catalyst interactions in the [3 + 2]-cycloaddition reactions of metalated azomethine ylides.

  8. Divergent Synthesis of Multisubstituted Tetrahydrofurans and Pyrrolidines via Intramolecular Aldol-type Trapping of Onium Ylide Intermediates.

    PubMed

    Jing, Changcheng; Xing, Dong; Gao, Lixin; Li, Jia; Hu, Wenhao

    2015-12-21

    This paper reports a divergent strategy for the synthesis of multisubstituted tetrahydrofurans and pyrrolidines, starting from easily accessible β-hydroxyketones or β-aminoketones to react with diazo compounds. Under Rh(II) catalysis, this transformation is proposed to proceed through a metal-carbene-induced oxonium ylide or ammonium ylide formation followed by an intramolecular aldol-type trapping of these active intermediates. A series of highly substituted tetrahydrofurans and pyrrolidines are synthesized in high yields with good to excellent diastereoselectivities. Preliminary biological evaluations revealed that both types of heterocycles show good PTP1B inhibitory activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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

  10. (4 + 3) Cycloadditions of Nitrogen-Stabilized Oxyallyl Cations

    PubMed Central

    Lohse, Andrew G.; Hsung, Richard P.

    2011-01-01

    The use of heteroatom-substituted oxyallyl cations in (4 + 3) cycloadditions has had a tremendous impact on the development of cycloaddition chemistry. Extensive efforts have been exerted toward investigating the effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of oxyallyl cations. Most recently, the use of nitrogen-stabilized oxyallyl cations has gained prominence in the area of (4 + 3) cycloadditions. The following article will provide an overview of this concept utilizing nitrogen-stabilized oxyallyl cations. PMID:21384451

  11. Nickel-catalyzed cycloadditions of unsaturated hydrocarbons, aldehydes, and ketones.

    PubMed

    Tekavec, Thomas N; Louie, Janis

    2008-04-04

    The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3,3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon-carbon bond is formed, prior to a competitive beta-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No beta-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C-O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon-carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr).

  12. Nickel-Catalyzed Cycloadditions of Unsaturated Hydrocarbons, Aldehydes, and Ketones

    PubMed Central

    Tekavec, Thomas N.

    2014-01-01

    The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3, 3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon–carbon bond is formed, prior to a competitive β-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No β-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C–O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon–carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr). PMID:18318544

  13. Expeditious Preparation of Open-Cage Fullerenes by Rhodium(I)-Catalyzed [2+2+2] Cycloaddition of Diynes and C60: an Experimental and Theoretical Study.

    PubMed

    Artigas, Albert; Pla-Quintana, Anna; Lledó, Agustí; Roglans, Anna; Solà, Miquel

    2018-06-04

    A novel methodology to transform C60 into a variety of open-cage fullerene derivatives employing rhodium(I) catalysis has been developed. This transformation encompasses a partially intermolecular [2+2+2] cycloaddition reaction between diynes 1 and C60 to deliver a cyclohexadiene-fused fullerene, which concomitantly undergoes a formal [4+4]/retro-[2+2+2] rearrangement to deliver open-cage fullerenes 2. Most notably, this process occurs without the need of photoexcitation. The complete mechanism of this transformation has been rationalized by DFT calculations, which indicate that, after [2+2+2] cycloaddition, the cyclohexadiene-fused intermediate evolves into the final product through a Rh-catalyzed di-π-methane rearrangement followed by a retro-[2+2+2] cycloaddition. The obtained open-cage fullerenes can be derivatized by Suzuki-Miyaura cross-coupling, or subjected to ring expansion to deliver a 12-membered ring orifice in the fullerene structure. Overall, the methodology presented constitutes a straightforward entry to functional open-cage C60-fullerene derivatives employing catalytic methods. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Diels-Alder Cycloadditions of Masked o-Benzoquinones with Alkenes.

    PubMed

    Georgopanou, Effie; Martini, Katerina-Irene; Pantazis, Panagiotis; Pelagias, Paulos; Voulgari, Penelope; Hadjiarapoglou, Lazaros P

    2015-10-02

    Diels-Alder cycloadditions of 3-oxobut-1-enyl substituted orthoquinone monoketals with olefinic dienophiles furnished functionalized ortho-endo bicyclo[2.2.2]octenone derivatives with high regio- and stereoselectivities. The competition between self-dimerization and Diels-Alder cycloaddition with an external dienophile usually exists, except in the case of 5-substituted orthoquinone monoketal.

  15. Cycloaddition Reactions of Cobalt-Complexed Macrocyclic Alkynes: The Transannular Pauson-Khand Reaction.

    PubMed

    Karabiyikoglu, Sedef; Boon, Byron A; Merlic, Craig A

    2017-08-04

    The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2 + 2 + 1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Macrocyclic enyne and dienyne complexes were readily synthesized by palladium(II)-catalyzed oxidative macrocyclizations of bis(vinyl boronate esters) or ring-closing metathesis reactions followed by complexation with dicobalt octacarbonyl. Several reaction modalities of these macrocyclic complexes were uncovered. In addition to the first successful transannular Pauson-Khand reactions, other intermolecular and transannular cycloaddition reactions included intermolecular Pauson-Khand reactions, transannular [4 + 2] cycloaddition reactions, intermolecular [2 + 2 + 2] cycloaddition reactions, and intermolecular [2 + 2 + 1 + 1] cycloaddition reactions. The structural and reaction requirements for each process are presented.

  16. Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A†

    PubMed Central

    Lozama, Anthony; Cunningham, Christopher W.; Caspers, Michael J.; Douglas, Justin T.; Dersch, Christina M.; Rothman, Richard B.; Prisinzano, Thomas E.

    2011-01-01

    As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan containing natural products. PMID:21338114

  17. Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.

    PubMed

    Lozama, Anthony; Cunningham, Christopher W; Caspers, Michael J; Douglas, Justin T; Dersch, Christina M; Rothman, Richard B; Prisinzano, Thomas E

    2011-04-25

    As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products.

  18. Brønsted acid-catalyzed decarboxylative redox amination: formation of N-alkylindoles from azomethine ylides by isomerization.

    PubMed

    Mao, Hui; Wang, Sichang; Yu, Peng; Lv, Huiqing; Xu, Runsheng; Pan, Yuanjiang

    2011-02-18

    A Brønsted acid-catalyzed decarboxylative redox amination involving aldehydes with 2-carboxyindoline for the synthesis of N-alkylindoles is described. The decarboxylative condensations of aldehydes with 2-carboxyindoline produce azomethine ylides in situ, which then transform into N-alkylindoles by isomerization. © 2011 American Chemical Society

  19. An Expedient Regio- and Diastereoselective Synthesis of Hybrid Frameworks with Embedded Spiro[9,10]dihydroanthracene [9,3']-pyrrolidine and Spiro[oxindole-3,2'-pyrrolidine] Motifs via an Ionic Liquid-Mediated Multicomponent Reaction.

    PubMed

    Arumugam, Natarajan; Almansour, Abdulrahman I; Kumar, Raju Suresh; Menéndez, J Carlos; Sultan, Mujeeb A; Karama, Usama; Ghabbour, Hazem A; Fun, Hoong-Kun

    2015-09-03

    A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields.

  20. Phosphorus and Sulfur Ylide Formation: Preparation of 1-Bensoyl-2-phenylcyclopropane and 1,4-diphenyl-1,3-butadiene by Phase Transfer Catalysis.

    ERIC Educational Resources Information Center

    Lampman, Gary M.; And Others

    1985-01-01

    Describes the use of phase transfer conditions to prepare a sulfur and phosphorus ylide. Background information and procedures are provided for the experiment (which can be completed in one three-hour laboratory period). (JN)

  1. Nitrenes, carbenes, diradicals, and ylides. Interconversions of reactive intermediates.

    PubMed

    Wentrup, Curt

    2011-06-21

    Rearrangements of aromatic and heteroaromatic nitrenes and carbenes can be initiated with either heat or light. The thermal reaction is typically induced by flash vacuum thermolysis, with isolation of the products at low temperatures. Photochemical experiments are conducted either under matrix isolation conditions or in solution at ambient temperature. These rearrangements are usually initiated by ring expansion of the nitrene or carbene to a seven-membered ring ketenimine, carbodiimide, or allene (that is, a cycloheptatetraene or an azacycloheptatetraene when a nitrogen is involved). Over the last few years, we have found that two types of ring opening take place as well. Type I is an ylidic ring opening that yields nitrile ylides or diazo compounds as transient intermediates. Type II ring opening produces either dienylnitrenes (for example, from 2-pyridylnitrenes) or 1,7-(1,5)-diradicals (such as those formed from 2-quinoxalinylnitrenes), depending on which of these species is better stabilized by resonance. In this Account, we describe our achievements in elucidating the nature of the ring-opened species and unraveling the connections between the various reactive intermediates. Both of these ring-opening reactions are found, at least in some cases, to dominate the subsequent chemistry. Examples include the formation of ring-opened ketenimines and carbodiimides, as well as the ring contraction reactions that form five-membered ring nitriles (such as 2- and 3-cyanopyrroles from pyridylnitrenes, N-cyanoimidazoles from 2-pyrazinyl and 4-pyrimidinylnitrenes, N-cyanopyrazoles from 2-pyrimidinylnitrenes and 3-pyridazinylnitrenes, and so forth). The mechanisms of formation of the open-chain and ring-contraction products were unknown at the onset of this study. In the course of our investigation, several reactions with three or more consecutive reactive intermediates have been unraveled, such as nitrene, seven-membered cyclic carbodiimide, and open-chain nitrile ylide

  2. Computational Insights into an Enzyme-Catalyzed [4+2] Cycloaddition

    PubMed Central

    2017-01-01

    The enzyme SpnF, involved in the biosynthesis of spinosyn A, catalyzes a formal [4+2] cycloaddition of a 22-membered macrolactone, which may proceed as a concerted [4+2] Diels–Alder reaction or a stepwise [6+4] cycloaddition followed by a Cope rearrangement. Quantum mechanics/molecular mechanics (QM/MM) calculations combined with free energy simulations show that the Diels–Alder pathway is favored in the enzyme environment. OM2/CHARMM free energy simulations for the SpnF-catalyzed reaction predict a free energy barrier of 22 kcal/mol for the concerted Diels–Alder process and provide no evidence of a competitive stepwise pathway. Compared with the gas phase, the enzyme lowers the Diels–Alder barrier significantly, consistent with experimental observations. Inspection of the optimized geometries indicates that the enzyme may prearrange the substrate within the active site to accelerate the [4+2] cycloaddition and impede the [6+4] cycloaddition through interactions with active-site residues. Judging from partial charge analysis, we find that the hydrogen bond between the Thr196 residue of SpnF and the substrate C15 carbonyl group contributes to the enhancement of the rate of the Diels–Alder reaction. QM/MM simulations show that the substrate can easily adopt a reactive conformation in the active site of SpnF because interconversion between the C5–C6 s-trans and s-cis conformers is facile. Our QM/MM study suggests that the enzyme SpnF does behave as a Diels-Alderase. PMID:29131960

  3. 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

  4. Exploiting [2+2] cycloaddition chemistry: achievements with allenes.

    PubMed

    Alcaide, Benito; Almendros, Pedro; Aragoncillo, Cristina

    2010-02-01

    The allene moiety represents an excellent partner for the [2+2] cycloaddition with alkenes and alkynes, affording the cyclobutane and cyclobutene skeletons in a single step. This strategy has been widely studied under thermal, photochemical and microwave induced conditions. More recently, the use of transition metal catalysis has been introduced as an alternative relying on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of polycyclic compounds in a regio- and stereoselective fashion. This critical review focuses on the most recently developed [2+2] cycloadditions on allenes along with remarkable early works accounting for the mechanism, the regio- and diastereoselectivity of the cycloadducts formed (103 references).

  5. Gold-Catalyzed Formal [4+1]/[4+3] Cycloadditions of Diazo Esters with Triazines.

    PubMed

    Zhu, Chenghao; Xu, Guangyang; Sun, Jiangtao

    2016-09-19

    Reported herein is the unprecedented gold-catalyzed formal [4+1]/[4+3] cycloadditions of diazo esters with hexahydro-1,3,4-triazines, thus providing five- and seven-membered heterocycles in moderate to high yields under mild reaction conditions. These reactions feature the use of a gold complex to accomplish the diverse annulations and the first example of the involvement of a gold metallo-enolcarbene in a cycloaddition. It is also the first utilization of stable triazines as formal dipolar adducts in the carbene-involved cycloadditions. Mechanistic investigations reveal that the triazines reacted directly, rather than as formaldimine precursors, in the reaction process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Rapid cycloaddition of a diazo group with an unstrained dipolarophile.

    PubMed

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

    2016-06-01

    The cycloaddition of a diazoacetamide with ethyl 4,4,4-trifluorocrotonate proceeds with k = 0.1 M -1 s -1 . This second-order rate constant rivals those of optimized strain-promoted azide- alkyne cycloadditions, even though the reaction does not release strain. The regioselectivity and a computational distortion/interaction analysis of the reaction energetics are consistent with the formation of an N-H…F-C hydrogen bond in the transition state and the electronic character of the trifluorocrotonate. Analogous reactions with an azidoacetamide dipole or with an acrylate or crotonate dipolarophile were much slower. These findings suggest a new strategy for the design of diazo-selective reagents for chemical biology.

  7. Isoxazolodihydropyridinones: 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines

    PubMed Central

    Coffman, Keith C.; Hartley, Timothy P.; Dallas, Jerry L.; Kurth, Mark J.

    2012-01-01

    Practical and efficient methods have been developed for the diversity-oriented synthesis of isoxazolodihydropyridinones via the 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines. A select few of these isoxazolodihydropyridinones were further elaborated with triazoles by copper catalyzed azide-alkyne cycloaddition reactions. A total of 70 compounds and intermediates were synthesized and analyzed for drug likeness. Sixty-four of these novel compounds were submitted to the NIH Molecular Libraries Small Molecule Repository for high-throughput biological screening. PMID:22352295

  8. Kinetics studies of rapid strain-promoted [3 + 2]-cycloadditions of nitrones with biaryl-aza-cyclooctynone.

    PubMed

    McKay, Craig S; Chigrinova, Mariya; Blake, Jessie A; Pezacki, John Paul

    2012-04-21

    Strain-promoted cycloadditions of cyclic nitrones with biaryl-aza-cyclooctynone (BARAC) proceed with rate constants up to 47.3 M(-1) s(-1), this corresponds to a 47-fold rate enhancement relative to reaction of BARAC with benzyl azide and a 14-fold enhancement over previously reported strain promoted alkyne-nitrone cycloadditions (SPANC). Studies of the SPANC reaction using the linear free energy relationship defined by the Hammett equation demonstrated that the cycloaddition reaction has a rho value of 0.25 ± 0.04, indicating that reaction is not sensitive to substituents and thus should have broad applicability. This journal is © The Royal Society of Chemistry 2012

  9. An intramolecular [2 + 2] cycloaddition of ketenimines via palladium-catalyzed rearrangements of N-allyl-ynamides.

    PubMed

    DeKorver, Kyle A; Hsung, Richard P; Song, Wang-Ze; Wang, Xiao-Na; Walton, Mary C

    2012-06-15

    A cascade of Pd-catalyzed N-to-C allyl transfer-intramolecular ketenimine-[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines.

  10. Iron-catalyzed intermolecular cycloaddition of diazo surrogates with hexahydro-1,3,5-triazines.

    PubMed

    Liu, Pei; Zhu, Chenghao; Xu, Guangyang; Sun, Jiangtao

    2017-09-26

    We report here an unprecedented iron-catalyzed cycloaddition reaction of diazo surrogates with hexahydro-1,3,5-triazines, providing five-membered heterocycles in moderate to high yields under mild reaction conditions. This cycloaddition features C-N and C-C bond formation using a cheap iron catalyst. Importantly, different to our former report on a gold-catalyzed system, both donor/donor and donor/acceptor diazo substrates are tolerated in this iron-catalyzed protocol.

  11. 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.

  12. An Intramolecular [2 + 2] Cycloaddition of Ketenimines via Palladium-Catalyzed Rearrangements of N-Allyl-Ynamides

    PubMed Central

    DeKorver, Kyle A.; Song, Wang-Ze; Wang, Xiao-Na; Walton, Mary C.

    2012-01-01

    A cascade of Pd-catalyzed N-to-C allyl transfer–intramolecular ketenimine–[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines. PMID:22667819

  13. Direct Enantioselective Reaction between Hemiacetals and Phosphorus Ylides: Important Role of a By-Product in the Asymmetric Transformation.

    PubMed

    Wang, Rui; Wang, Linqing; Yang, Dongxu; Li, Dan; Liu, Xihong; Wang, Pengxin; Wang, Kezhou; Zhu, Haiyong; Bai, Lutao

    2018-05-16

    By employing a simple in-situ generated magnesium catalyst, the direct asymmetric reaction between hemiacetals and P-ylides is achieved via a tandem Wittig-oxa-Michael reaction sequence. Enantioenriched chromans, isochromans and tetrahydropyrans can be obtained in good chemical yields. (-)-Erythrococcamide B can be asymmetrically synthesized through this synthetic technique. In this work, the by-product, TPO, was identified as a necessary additive in this asymmetric synthetic method. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives.

    PubMed

    Al Matarneh, Cristina M; Mangalagiu, Ionel I; Shova, Sergiu; Danac, Ramona

    2016-01-01

    A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo- and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer.

  15. Fused tetracycles with a benzene or cyclohexadiene core: [2 + 2 + 2] cycloadditions on macrocyclic systems.

    PubMed

    Brun, Sandra; Garcia, Lídia; González, Iván; Torrent, Anna; Dachs, Anna; Pla-Quintana, Anna; Parella, Teodor; Roglans, Anna

    2008-09-28

    A series of fused tetracycles with a benzene or cyclohexadiene core (2a-h) is satisfactorily prepared by intramolecular [2 + 2 + 2] cycloadditions of triynic and enediynic macrocycles (1a-h) under RhCl(PPh3)3 catalysis; the enantioselective cycloaddition of macrocycles 1b and 1e and gives chiral tetracycles with moderate enantiomeric excess.

  16. Studies on the Himbert Intramolecular Arene/ Allene Diels – Alder Cycloaddition. Mechanistic Studies and Expansion of Scope to All-Carbon Tethers

    PubMed Central

    Schmidt, Yvonne; Lam, Jonathan K.; Pham, Hung V.; Houk, K. N.; Vanderwal, Christopher D.

    2013-01-01

    The unusual intramolecular arene/allene cycloaddition described thirty years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds. To more fully understand the mechanism of this cycloaddition reaction, and to guide efforts to extend its scope to new substrates, quantum mechanical computational methods were employed in concert with laboratory experiments. These studies indicated that the cycloadditions likely proceed via concerted processes; a stepwise biradical mechanism was shown to be higher in energy in the cases studied. The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems, with computational guidance used to predict thermodynamically favorable cases. Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring-rearrangement metathesis reactions. PMID:23634642

  17. Stepwise π-extension of meso-alkylidenyl porphyrins through sequential 1,3-dipolar cycloaddition and redox reactions.

    PubMed

    Park, Dowoo; Jeong, Seung Doo; Ishida, Masatoshi; Lee, Chang-Hee

    2014-08-25

    Several regioselectively π-extended, pyrrole fused porphyrinoids have been synthesized by the 1,3-dipolar cycloaddition of meso-alkylidene-(benzi)porphyrins. Pd(II) complexes gave oxidation resistant, bis-pyrrole fused adducts. The repeated 1,3-dipolar cycloaddition followed by oxidation-reduction of pentaphyrin analogs afforded π-extended porphyrin analogs.

  18. Phosphine-catalyzed cycloadditions of allenic ketones: new substrates for nucleophilic catalysis.

    PubMed

    Wallace, Debra J; Sidda, Rachel L; Reamer, Robert A

    2007-02-02

    A range of phosphine-catalyzed cycloaddition reactions of allenic ketones have been studied, extending the scope of these processes from the more widely used 2,3-butadienoates to allow access to a number of synthetically useful products. Reaction of allenyl methyl ketone 4 with exo-enones afforded spirocyclic compounds in good regioselectivity and promising enantioselectivity via a [2 + 3] cycloaddtion. Aromatic allenyl ketones undergo a phosphine-promoted dimerization to afford functionalized pyrans, leading to a formal [2 + 4] Diels-Alder product, but did not react in the [2 + 3] cycloaddition. The results from other reactions that had found utility with 2,3-butadienoates are also reported.

  19. Mercury(II) complexes of unsymmetric phosphorus ylides: Synthesis, spectroscopic and antibacterial activity studies

    NASA Astrophysics Data System (ADS)

    Sabounchei, Seyyed Javad; Panahimehr, Mohammad; Hosseinzadeh, Marjan; Karamian, Roya; Asadbegy, Mostafa; Masumi, Azadeh

    2014-03-01

    The reaction of Ph2PCH2PPh2 (dppm) with 2-bromo-3-nitroacetophenone and 2,2‧,4‧-trichloroacetophenone in chloroform produce the new phosphonium salts [Ph2PCH2PPh2CH2C(O)C6H4NO2]Br (1) and [Ph2PCH2PPh2CH2C(O)C6H3Cl2]Cl (2). Further, by reaction of the monophosphonium salts of dppm with the strong base triethylaminethe corresponding bidentate phosphorus ylides, Ph2PCH2PPh2C(H)C(O)C6H4NO2 (3) and Ph2PCH2PPh2C(H)C(O)C6H3Cl2 (4) were obtained. The reaction of these ligands with mercury(II) halides in dry methanol led to the formation of the mononuclear complexes {HgX2[(Ph2PCH2PPh2C(H)C(O)C6H4NO2)]} [X = Cl (5), Br (6), I (7)] and {HgX2[(Ph2PCH2PPh2C(H)C(O)C6H3Cl2)]} [X = Cl (8), Br (9), I (10)]. Characterization of the obtained compounds was performed by elemental analysis, IR, 1H, 31P and 13C NMR. The structure of compound 1 being unequivocally determined by single crystal X-ray diffraction techniques. The mass spectrum of compound 6 (as an instance) also demonstrates the synthesize of these compounds. In all complexes the title ylides are coordinated through the ylidic carbon and the phosphine atom. These compounds form five membered ring under complexation. The antibacterial effects of DMSO solutions of the ligands and their metal complexes were evaluated by the disc diffusion method against six Gram positive and negative bacteria. All compounds represent antibacterial activity against these bacteria with high levels of inhibitory potency exhibited against the Gram positive species.

  20. 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…

  1. Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling.

    PubMed

    Chandrasoma, Nalin; Brown, Neil; Brassfield, Allen; Nerurkar, Alok; Suarez, Susana; Buszek, Keith R

    2013-02-20

    An efficient total synthesis of the annulated indole natural product (±)- cis -trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal-halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber-Batcho indole synthesis.

  2. Diazo Esters as Dienophiles in Intramolecular (4 + 2) Cycloadditions: Computational Explorations of Mechanism.

    PubMed

    Duan, Abing; Yu, Peiyuan; Liu, Fang; Qiu, Huang; Gu, Feng Long; Doyle, Michael P; Houk, K N

    2017-02-22

    The first experimental examples of Diels-Alder (DA) reactions of diazo compounds as heterodienophiles with dienes have been studied with density functional theory (DFT) using the M06-2X functional. For comparison, the reactivities of diazo esters as dienophiles or 1,3-dipoles with 1,3-dienes in intermolecular model systems have been analyzed by the distortion/interaction model. The 1,3-dipolar cycloaddition is strongly favored for the intermolecular system. The intramolecular example is unique because the tether strongly favors the (4 + 2) cycloaddition.

  3. 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.

  4. Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

    PubMed

    Furnival, Rachel C; Saruengkhanphasit, Rungroj; Holberry, Heather E; Shewring, Jonathan R; Guerrand, Hélène D S; Adams, Harry; Coldham, Iain

    2016-11-22

    Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine.

  5. Peptidomimetics via copper-catalyzed azide-alkyne cycloadditions.

    PubMed

    Angell, Yu L; Burgess, Kevin

    2007-10-01

    This critical review concerns the impact of copper-mediated alkyne-azide cycloadditions on peptidomimetic studies. It discusses how this reaction has been used to insert triazoles into peptide chains, to link peptides to other functionalities (e.g. carbohydrates, polymers, and labels), and as a basis for evolution of less peptidic compounds as pharmaceutical leads. It will be of interest to those studying this click reaction, peptidomimetic secondary structure and function, and to medicinal chemists.

  6. Catalytic asymmetric trifluoromethylthiolation via enantioselective [2,3]-sigmatropic rearrangement of sulfonium ylides

    NASA Astrophysics Data System (ADS)

    Zhang, Zhikun; Sheng, Zhe; Yu, Weizhi; Wu, Guojiao; Zhang, Rui; Chu, Wen-Dao; Zhang, Yan; Wang, Jianbo

    2017-10-01

    The trifluoromethylthio (SCF3) functional group has been of increasing importance in drug design and development as a consequence of its unique electronic properties and high stability coupled with its high lipophilicity. As a result, methods to introduce this highly electronegative functional group have attracted considerable attention in recent years. Although significant progress has been made in the introduction of SCF3 functionality into a variety of molecules, there remain significant challenges regarding the enantioselective synthesis of SCF3-containing compounds. Here, an asymmetric trifluoromethylthiolation that proceeds through the enantioselective [2,3]-sigmatropic rearrangement of a sulfonium ylide generated from a metal carbene and sulfide (Doyle-Kirmse reaction) has been developed using chiral Rh(II) and Cu(I) catalysts. This transformation features mild reaction conditions and excellent enantioselectivities (up to 98% yield and 98% e.e.), thus providing a unique, highly efficient and enantioselective method for the construction of C(sp3)-SCF3 bonds bearing chiral centres.

  7. Microwave-based reaction screening: tandem retro-Diels-Alder/Diels-Alder cycloadditions of o-quinol dimers.

    PubMed

    Dong, Suwei; Cahill, Katharine J; Kang, Moon-Il; Colburn, Nancy H; Henrich, Curtis J; Wilson, Jennifer A; Beutler, John A; Johnson, Richard P; Porco, John A

    2011-11-04

    We have accomplished a parallel screen of cycloaddition partners for o-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels-Alder/Diels-Alder cascades of o-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels-Alder cycloadditions of o-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor.

  8. Gold (I)-Catalyzed Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition and Mannich Reactions of Azlactones

    PubMed Central

    Melhado, Asa D.; Amarante, Giovanni W.; Wang, Z. Jane; Luparia, Marco; Toste, F. Dean

    2011-01-01

    Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold-catalysts, namely C2-symmetric bis(phosphinegold(I) carboxylate)complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes, and the chemistry of the resultant cycloadducts, are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem MS studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component. PMID:21341677

  9. Synthesis of Trifluoromethylated Isoxazolidines: 1,3-Dipolar Cycloaddition of Nitrosoarenes, (Trifluoromethyl)diazomethane, and Alkenes

    PubMed Central

    Molander, Gary A.; Cavalcanti, Livia N.

    2013-01-01

    Isoxazolidines have proven to be important substrates in synthetic organic chemistry. Limited examples in the literature that provide trifluoromethylated versions of these compounds have prompted us to investigate a 1,3-dipolar cycloaddition route providing access to N-functionalized isoxazolidines containing a trifluoromethyl group. Thus, a 1,3-dipolar cycloaddition of nitrosoarenes, (trifluoromethyl)diazomethane, and alkenes was developed. The starting materials can be synthesized from easy to handle and accessible reagents. The reaction proved to be tolerant of a variety of electron-deficient alkenes and nitrosoarenes. PMID:24490778

  10. Synthesis of δ- and α-Carbolines via Nickel-Catalyzed [2 + 2 + 2] Cycloaddition of Functionalized Alkyne-Nitriles with Alkynes.

    PubMed

    Wang, Gaonan; You, Xu; Gan, Yi; Liu, Yuanhong

    2017-01-06

    A new method for the synthesis of δ- and α-carbolines through Ni-catalyzed [2 + 2 + 2] cycloaddition of ynamide-nitriles or alkyne-cyanamides with alkynes has been developed. The catalytic system of NiCl 2 (DME)/dppp/Zn with a low-cost Ni(II)-precursor was first utilized in Ni-catalyzed [2 + 2 + 2] cycloaddition reactions, and the in situ generated Lewis acid may play an important role for the successful transformation. Not only internal alkynes but also terminal alkynes undergo the desired cycloaddition reactions efficiently to furnish the carboline derivatives with wide diversity and functional group tolerance.

  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. 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

  13. Diazo Compounds as Highly Tunable Reactants in 1,3-Dipolar Cycloaddition Reactions with Cycloalkynes†

    PubMed Central

    McGrath, Nicholas A.

    2012-01-01

    Diazo compounds, which can be accessed directly from azides by deimidogenation, are shown to be extremely versatile dipoles in 1,3-dipolar cycloaddition reactions with a cyclooctyne. The reactivity of a diazo compound can be much greater or much less than its azide analog, and is enhanced markedly in polar-protic solvents. These reactivities are predictable from frontier molecular orbital energies. The most reactive diazo compound exhibited the highest known second-order rate constant to date for a dipolar cycloaddition with a cycloalkyne. These data provide a new modality for effecting chemoselective reactions in a biological context. PMID:23227302

  14. 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

  15. The influence of reaction conditions on the Diels-Alder cycloadditions of 2-thio-3-chloroacrylamides; investigation of thermal, catalytic and microwave conditions.

    PubMed

    Kissane, Marie; Lynch, Denis; Chopra, Jay; Lawrence, Simon E; Maguire, Anita R

    2010-12-21

    The Diels-Alder cycloadditions of cyclopentadiene and 2,3-dimethyl-1,3-butadiene to a range of 2-thio-3-chloroacrylamides under thermal, catalytic and microwave conditions is described. The influence of reaction conditions on the outcome of the cycloadditions, in particular the stereoselectivity and reaction efficiency, is discussed. While the cycloadditions have been attempted at the sulfide, sulfoxide and sulfone levels of oxidation, use of the sulfoxide derivatives is clearly beneficial for stereoselective construction of Diels-Alder cycloadducts.

  16. Cu(OAc)2/TFA-promoted formal [3 + 3] cycloaddition/oxidation of enamines and enones for synthesis of multisubstituted aromatic amines.

    PubMed

    Li, Liang; Zhao, Mi-Na; Ren, Zhi-Hui; Li, Jian-Li; Guan, Zheng-Hui

    2012-07-06

    New strategies for the oxidative cycloaddition of enones with enamines are developed. These cycloaddition reactions directly afford substituted aromatic amines, which are important in organic chemistry, in moderate to good yield. Cu(OAc)(2)/TFA is shown to be essential to achieve high reaction efficiency.

  17. From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions

    PubMed Central

    2011-01-01

    Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Examples from the past decade suggest that a promising strategy for bioorthogonal reaction development begins with an analysis of functional group and reactivity space outside those defined by Nature. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. Finally, the reaction must be tested in a variety of environments, escalating from aqueous media to biomolecule solutions to cultured cells and, for the most optimized transformations, to live organisms. Work in our laboratory led to the development of two bioorthogonal transformations that exploit the azide as a small, abiotic, and bioinert reaction partner: the Staudinger ligation and strain-promoted azide–alkyne cycloaddition. The Staudinger ligation is based on the classic Staudinger reduction of azides with triarylphosphines first reported in 1919. In the ligation reaction, the intermediate aza-ylide undergoes intramolecular reaction with an ester, forming an amide bond faster than aza-ylide hydrolysis would otherwise occur in water. The Staudinger ligation is highly selective and reliably forms its product in environs as demanding as live mice. However, the Staudinger ligation has some liabilities, such as the propensity of phosphine reagents to undergo air oxidation and the relatively slow kinetics of the reaction. The Staudinger ligation takes

  18. Diels-Alder cycloaddition in the synthesis of 1-azafagomine, analogs, and derivatives as glycosidase inhibitors.

    PubMed

    Salgueiro, Daniela A L; Sousa, Cristina E A; Fortes, A Gil; Alves, M José

    2012-12-01

    This comprehensive review deals with the synthesis of 1-azafagomine, analogs, and derivatives having the Diels-Alder cycloaddition as the key step. Most of the compounds referred are racemic or have been resolved by lipase transesterification. There are two asymmetric cycloadditions leading to 1-azafagomine or to an analog. In one case both enantiomers of 1-azafagomine were prepared together with a pair of derivatives. The study comprises glycosidase inhibition studies of the target compounds to a set of glycosidic enzymes, and evidenced molecular features that enhance or diminish their activity as glycosidase inhibitors.

  19. Copper-catalyzed, C-C coupling-based one-pot tandem reactions for the synthesis of benzofurans using o-iodophenols, acyl chlorides, and phosphorus ylides.

    PubMed

    Liu, Yunyun; Wang, Hang; Wan, Jie-Ping

    2014-11-07

    One-pot reactions involving acyl chlorides, phosphorus ylides, and o-iodophenols with copper catalysis have been established for the rapid synthesis of functionalized benzofurans. With all of these easily available and stable reactants, the construction of the target products has been accomplished via tandem transformations involving a key C-C coupling, leading to the formation of one C(sp(2))-C bond, one C(sp(2))-O bond, and one C ═ C bond.

  20. Microwave-assisted synthesis of 3,6-di(pyridin-2-yl)pyridazines: unexpected ketone and aldehyde cycloadditions.

    PubMed

    Hoogenboom, Richard; Moore, Brian C; Schubert, Ulrich S

    2006-06-23

    3,6-Di(pyridin-2-yl)pyridazines are an interesting class of compounds because of their metal-coordinating ability resulting in the self-assembly into [2x2] gridlike metal complexes with copper(I) or silver(I) ions. These and other substituted pyridazines can be prepared by the inverse-electron-demand Diels-Alder reactions between acetylenes and 1,2,4,5-tetrazines. In this contribution, the effect of (superheated) microwave conditions on these generally slow cycloadditions is described. The cycloaddition of acetylenes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine could be accelerated from several days reflux in toluene or N,N-dimethylformamide to several hours in dichloromethane at 150 degrees C. In addition, the unexpected cycloaddition of the enol tautomers of various ketones and aldehydes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine is described in detail providing an alternative route for the synthesis of (substituted) pyridazines.

  1. Catalyst-free synthesis of skipped dienes from phosphorus ylides, allylic carbonates, and aldehydes via a one-pot SN2' allylation-Wittig strategy.

    PubMed

    Xu, Silong; Zhu, Shaoying; Shang, Jian; Zhang, Junjie; Tang, Yuhai; Dou, Jianwei

    2014-04-18

    A catalyst-free allylic alkylation of stabilized phosphorus ylides with allylic carbonates via a regioselective SN2' process is presented. Subsequent one-pot Wittig reaction with both aliphatic and aromatic aldehydes as well as ketenes provides structurally diverse skipped dienes (1,4-dienes) in generally high yields and moderate to excellent stereoselectivity with flexible substituent patterns. This one-pot SN2' allylation-Wittig strategy constitutes a convenient and efficient synthetic method for highly functionalized skipped dienes from readily available starting materials.

  2. Rh(I)-catalyzed Pauson-Khand-type cycloaddition reaction of ene-vinylidenecyclopropanes with carbon monoxide (CO).

    PubMed

    Yuan, Wei; Dong, Xiang; Shi, Min; McDowell, Patrick; Li, Guigen

    2012-11-02

    An intramolecular Pauson-Khand type cycloaddition reaction of ene-vinylidenecyclopropanes with carbon monoxide has been established by using [Rh(COD)Cl](2) as the catalyst. The reaction was found to be highly efficient in solvents of 1,2-dichloroethane and 1,1,2,2-tetrachloroethane to give excellent yields of 90-99%. The reaction provides easy access to a series of fused 6,5-ring structures containing spiro-cyclopropane units that are useful for drug design and development. A mechanism of this cycloaddition process has been proposed accounting for structures of resulting products that were unambiguously assigned by X-ray diffractional analysis.

  3. Synthesis of functionalized indolizidines through Pauson-Khand cycloaddition of 2-allylpyrrolidines.

    PubMed

    McCormack, Michael P; Waters, Stephen P

    2013-02-01

    A concise entry to functionalized indolizidine scaffolds through a domino 2-aza-Cope-[3 + 2] dipolar cycloaddition and Pauson-Khand [2 + 2 + 1] cyclization has been accomplished. The process was conducted under mild conditions to afford diverse indolizidine systems as single diastereomers in good overall yields.

  4. Synthesis of Functionalized Indolizidines through Pauson–Khand Cycloaddition of 2-Allylpyrrolidines

    PubMed Central

    McCormack, Michael P.

    2013-01-01

    A concise entry to functionalized indolizidine scaffolds through a domino 2-aza-Cope-[3+2] dipolar cycloaddition and Pauson–Khand [2+2+1] cyclization has been accomplished. The process was conducted under mild conditions to afford diverse indolizidine systems as single diastereomers in good overall yields. PMID:23311620

  5. Tin(IV) chloride catalyzed cycloaddition reactions between 3-ethoxycyclobutanones and allylsilanes.

    PubMed

    Matsuo, Jun-ichi; Sasaki, Shun; Hoshikawa, Takaya; Ishibashi, Hiroyuki

    2009-09-03

    Formal [4 + 2] cycloaddition between various 3-ethoxycyclobutanones and allyltrialkylsilanes proceeded to give 3-ethoxy-5-[(trialkylsilyl)methyl]cyclohexan-1-ones by catalysis with tin(VI) chloride. The use of allyl-tert-butyldiphenylsilane induced 1,5-hydride transfer, which gave 2-[3-(tert-butyldiphenylsilyl)propyl]-6-methyltetrahydro-4-pyrones.

  6. Visible Light Photocatalysis of [2+2] Styrene Cycloadditions via Energy Transfer

    PubMed Central

    Lu, Zhan; Yoon, Tehshik P.

    2012-01-01

    Hip to be square: Styrenes participate in [2+2] cycloadditions upon irradiation with visible light in the presence of an iridium(III) polypyridyl complex. In contrast to previous reports of visible light photoredox catalysis, the mechanism of this process involves photosensitization by energy transfer and not electron transfer. PMID:22965321

  7. Nitrile imines and nitrile ylides: rearrangements of benzonitrile N-methylimine and benzonitrile dimethylmethylide to azabutadienes, carbodiimides, and ketenimines. Chemical activation in thermolysis of azirenes, tetrazoles, oxazolones, isoxazolones, and oxadiazolones.

    PubMed

    Bégué, Didier; Dargelos, Alain; Berstermann, Hans M; Netsch, Klaus P; Bednarek, Pawel; Wentrup, Curt

    2014-02-07

    Flash vacuum thermolysis (FVT) of 1-methyl-5-phenyltetrazole (5b), 2-methyl-5-phenyltetrazole (1b), and 3-methyl-5-phenyl-1,3,4-oxadiazol-2(3H)-one (3b) affords the nitrile imine (2b), which rearranges in part to N-methyl-N'-phenylcarbodiimide (7b). Another part of 2b undergoes a 1,4-H shift to the diazabutadiene (13). 13 undergoes two chemically activated decompositions, to benzonitrile and CH2═NH and to styrene and N2. FVT of 2,2-dimethyl-4-phenyl-oxazol-5(2H)-one (16) at 400 °C yields 3-methyl-1-phenyl-2-azabutadiene (18) in high yield. In contrast, FVT of 3,3-dimethyl-2-phenyl-1-azirene (21) at 600 °C or 4,4-dimethyl-3-phenyl-isoxazolone (20) at 600 °C affords only a low yield of azabutadiene (18) due to chemically activated decomposition of 18 to styrene and acetonitrile. There are two reaction paths from azirene (21): one (path a) leading to nitrile ylide (17) and the major products styrene and acetonitrile and the other (path b) leading to the vinylnitrene (22) and ketenimine (23). The nitrile ylide PhC(-)═N(+)═C(CH3)2 (17) is implicated as the immediate precursor of azabutadiene (18). FVT of either 3-phenylisoxazol-5(4H)one (25) or 2-phenylazirene (26) at 600 °C affords N-phenylketenimine (28). The nitrile ylide PhC(-)═N(+)═CH2 (30) is postulated as a reversibly formed intermediate. N-Phenylketenimine (28) undergoes chemically activated free radical rearrangement to benzyl cyanide. The mechanistic interpretations are supported by calculations of the energies of key intermediates and transition states.

  8. Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl-ThDP.

    PubMed

    Alvarado, Omar; Jaña, Gonzalo; Delgado, Eduardo J

    2012-08-01

    In this study the formation of the lactyl-thiamin diphosphate intermediate (L-ThDP) is addressed using density functional theory calculations at X3LYP/6-31++G(d,p) level of theory. The study includes potential energy surface scans, transition state search, and intrinsic reaction coordinate calculations. Reactivity is analyzed in terms of Fukui functions. The results allow to conclude that the reaction leading to the formation of L-ThDP occurs via a concerted mechanism, and during the nucleophilic attack on the pyruvate molecule, the ylide is in its AP form. The calculated activation barrier for the reaction is 19.2 kcal/mol, in agreement with the experimental reported value.

  9. The asymmetric synthesis of terminal aziridines by methylene transfer from sulfonium ylides to imines.

    PubMed

    Kavanagh, Sarah A; Piccinini, Alessandro; Connon, Stephen J

    2013-06-07

    A new ylide-based protocol for the asymmetric aziridination of imines via methylene transfer has been developed involving the use of a simple chiral sulfonium salt and an organic strong base. A systematic study identified triisopropylphenyl sulfonylimines as optimal substrates for the process. Unexpectedly, hindered C2-symmetric sulfonyl salts incorporating bulky ethers at C-2 and C-5--which had previously been useful in the corresponding epoxidation chemistry--decomposed in these aziridination reactions via competing elimination pathways. Under optimised conditions it was found that a simple salt derived from (2R,5R)-2,5-diisopropyl thiolane could mediate asymmetric methylene transfer to a range of imines with uniformly excellent yields with 19-30% ee. Since this is a similar level of enantiomeric excess to that obtained using these same salts in epoxidation chemistry, it was concluded that if more bulky sulfonium salts could be devised which were resistant to decomposition under the reaction conditions, that highly enantioselective aziridine formation by methylene transfer would be possible.

  10. Rh(I)-catalyzed Pauson-Khand-type cycloaddition reaction of ene-vinylidenecyclopropanes with carbon monoxide (CO)

    PubMed Central

    Yuan, Wei; Dong, Xiang; McDowell, Patrick

    2012-01-01

    An intramolecular Pauson-Khand type cycloaddition reaction of ene-vinylidenecyclopropanes with carbon monoxide has been established by using [Rh(COD)Cl]2 as the catalyst. The reaction was found to be highly efficient in solvents of 1,2-dichloroethane and 1,1,2,2-tetrachloroethane to give excellent yields of 90 – 99%. The reaction provides easy access to a series of fused 6,5-ring structures containing spiro-cyclopropane units that are useful for drug design and development. A mechanism of this cycloaddition process has been proposed accounting for structures of resulting products that were unambiguously assigned by X-ray diffractional analysis. PMID:23098194

  11. 5-Hydroxyindoles by intramolecular alkynol-furan diels-alder cycloaddition.

    PubMed

    LaPorte, Matthew; Hong, Ki Bum; Xu, Jie; Wipf, Peter

    2013-01-04

    A convergent approach provides a convenient access to synthetically and biologically useful 3,4-disubstituted 5-hydroxyindoles. The one-pot procedure uses microwave heating to initiate an intramolecular [4 + 2]-cycloaddition of an alkynol segment onto a furan followed by a fragmentation, aromatization, and N-Boc deprotection cascade. Yields range from 15 to 74%, with aromatic substituents providing better conversions. 4-Trimethylsilylated analogues undergo a 1,3-silatropic rearrangement to give the O-TMS ethers.

  12. 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.

  13. Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade.

    PubMed

    Zhang, Hongjun; Boonsombat, Jutatip; Padwa, Albert

    2007-01-18

    A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].

  14. A Rhodium(I)-Xylyl-BINAP Catalyzed Asymmetric Ynamide-[2 + 2 + 2] Cycloaddition in the Synthesis of Optically Enriched N,O-Biaryls

    PubMed Central

    Oppenheimer, Jossian; Johnson, Whitney L.; Figueroa, Ruth; Hayashi, Ryuji; Hsung, Richard P.

    2009-01-01

    A rhodium(I)-xylyl-BINAP catalyzed asymmetric [2 + 2 + 2] cycloaddition of achiral conjugated aryl ynamides with various diynes is described here. This asymmetric cycloaddition provides a series of structurally interesting chiral N,O-biaryls with excellent enantioselectivity along with a modest diastereoselectivity with respect to both C-C and C-N axial chirality. PMID:20161177

  15. Formal [4+2] cycloaddition of di-tert-butyl 2-ethoxycyclobutane-1,1-dicarboxylate with ketones or aldehydes and tandem lactonization.

    PubMed

    Okado, Ryohei; Nowaki, Aya; Matsuo, Jun-Ichi; Ishibashi, Hiroyuki

    2012-01-01

    A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates, whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters.

  16. Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions.

    PubMed

    Alajarín, Mateo; Bonillo, Baltasar; Sanchez-Andrada, Pilar; Vidal, Angel; Bautista, Delia

    2007-07-20

    Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.

  17. 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.

  18. Rhodium-Catalyzed Acyloxy Migration of Propargylic Esters in Cycloadditions, Inspiration from Recent “Gold Rush”

    PubMed Central

    Shu, Xing-Zhong; Shu, Dongxu; Schienebeck, Casi M.

    2012-01-01

    Transition metal-catalyzed acyloxy migration of propargylic esters offers versatile entries to allene and vinyl carbene intermediates for various fascinating subsequent transformations. Most π-acidic metals (e.g. gold and platinum) are capable of facilitating these acyloxy migration events. However, very few of these processes involve redox chemistry, which are well-known for most other transition metals such as rhodium. The coupling of acyloxy migration of propargylic esters with oxidative addition, migratory insertion, and reductive elimination may lead to ample new opportunities for the design of new reactions. This tutorial review summarizes recent developments in Rh-catalyzed 1,3- and 1,2-acyloxy migration of propargylic esters in a number of cycloaddition reactions. Related Au- and Pt-catalyzed cycloadditions involving acyloxy migration are also discussed. PMID:22895533

  19. Synthesis of novel 16-spiro steroids: 7-(Aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo estrone hybrid heterocycles.

    PubMed

    Jeyachandran, Veerappan; Vivek Kumar, Sundaravel; Ranjith Kumar, Raju

    2014-04-01

    The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of isatins or acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from estrone afforded a library of novel C-16 spiro oxindole or acenaphthylene-1-one - 7-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole - estrone hybrid heterocycles. These reactions occur regio- and stereo-selectively affording a single isomer of the spiro estrones in excellent yields with the formation of two C-C and one C-N bonds along with the generation of four new contiguous stereo-centers in a single step. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Diels–Alder cycloaddition of 2-methylfuran and ethylene for renewable toluene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Green, Sara K.; Patet, Ryan E.; Nikbin, Nima

    Diels–Alder cycloaddition of biomass-derived 2-methylfuran and ethylene provides a thermochemical pathway to renewable toluene. In this work, the kinetics and reaction pathways of toluene formation have been evaluated with H-BEA and Sn-BEA catalysts. Kinetic analysis of the main reaction chemistries reveals the existence of two rate-controlling reactions: (i) Diels–Alder cycloaddition of 2-methylfuran and ethylene where the production rate is independent of the Brønsted acid site concentration, and (ii) dehydration of the Diels–Alder cycloadduct where the production rate is dependent on the Brønsted acid site concentration. Application of a reduced kinetic model supports the interplay of these two regimes with themore » highest concentration of toluene measured at a catalyst loading equal to the transition region between the two kinetic regimes. Selectivity to toluene never exceeded 46%, as 2-methylfuran was consumed by several newly identified reactions to side products, including dimerization of 2-methylfuran, the formation of a trimer following hydrolysis and ring-opening of 2-methylfuran, and the incomplete dehydration of the Diels–Alder cycloadduct of 2-methylfuran and ethylene.« less

  1. Total Synthesis of (±)-Strychnine via a [4+2]-Cycloaddition/Rearrangement Cascade

    PubMed Central

    Zhang, Hongjun; Boonsombat, Jutatip

    2008-01-01

    A new strategy for the synthesis of the Strychnos alkaloid (±)-strychnine has been developed and is based on an intramolecular [4+2]-cycloaddition/rearrangement cascade of an indolyl substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. PMID:17217284

  2. 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…

  3. 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

  4. The formal total synthesis of (+/-)-strychnine via a cobalt-mediated [2 + 2 + 2]cycloaddition.

    PubMed

    Eichberg, M J; Dorta, R L; Lamottke, K; Vollhardt, K P

    2000-08-10

    A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.

  5. 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...

  6. Synthesis of Single and Double Dibenzohelicenes by Rhodium-Catalyzed Intramolecular [2+2+2] and [2+1+2+1] Cycloaddition.

    PubMed

    Yamano, Ryota; Shibata, Yu; Tanaka, Ken

    2018-04-25

    Dibenzo[7]helicenes were synthesized with up to 99 % ee by rhodium(I)/binap-catalyzed enantioselective intramolecular [2+2+2] cycloaddition of 2-phenylnaphthalene-linked triynes. Additionally, [2+1+2+1] cycloaddition products, that is, twisted anthracenes, were also synthesized by using difluorphos as ligand. Although these compounds are not configurationally stable at elevated temperature, their Scholl reactions afforded configurationally stable double dibenzo[6]helicenes. The thus-obtained dibenzo[7]helicene exhibited good circularly polarized luminescence property and the double dibenzo[6]helicene showed high fluorescence quantum yield. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Catalytic asymmetric synthesis of chiral propargylic alcohols for the intramolecular Pauson-Khand cycloaddition.

    PubMed

    Turlington, Mark; Yue, Yang; Yu, Xiao-Qi; Pu, Lin

    2010-10-15

    Several methods for the catalytic asymmetric alkyne addition to aldehydes are used to prepare the propargylic alcohol-based chiral en-ynes. Protection of the propargylic alcohols with either an acetyl or a methyl group allows the resulting en-ynes to undergo the intramolecular Pauson-Khand reaction to form the corresponding optically active 5,5- and 5,6-fused bicyclic products with high diastereoselectivity and high enantiomeric purity. In the major product, the propargylic substituent and the bridgehead hydrogen are cis with respect to each other on the fused bicyclic rings. The enantiomeric purity of the propargylic alcohols generated from the asymmetric alkyne addition is maintained in the cycloaddition products. The allylic ethers of the chiral propargylic alcohols are prepared which can also undergo the highly diastereoselective Pauson-Khand cycloaddition with retention of the high enantiomeric purity. This study has shown that the size of the substituents at the propargylic position as well as on the alkyne is important for the diastereoselectivity with the greater bulkiness of the substituents giving higher diastereoselectivity.

  8. Intramolecular Parallel [4+3] Cycloadditions of Cyclopropane 1,1-Diesters with [3]Dendralenes: Efficient Construction of [5.3.0]Decane and Corresponding Polycyclic Skeletons.

    PubMed

    Zhang, Chi; Tian, Jun; Ren, Jun; Wang, Zhongwen

    2017-01-26

    Aiming to develop efficient and general strategies for construction of complex and diverse polycyclic skeletons, we have successfully developed [4+3]IMPC (intramolecular parallel cycloaddition) of cyclopropane 1,1-diesters with [3]dendralenes. With a combination of the [4+3]IMPC and subsequent [4+n] cycloadditions, trans-[5.3.0]decane skeleton and its corresponding structurally complex and diverse polycyclic variants could be constructed efficiently. This novel [4+3] cycloaddition reaction mode of donor-acceptor cyclopropanes proceeds as a result of the ring-strain relief of a trans-[3.3.0]octane. We strongly believe that the developed methods will demonstrate potential applications in natural products synthesis and drug discovery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes and CO: reaction design, development, application in natural product synthesis, and inspiration for developing new reactions for synthesis of eight-membered carbocycles.

    PubMed

    Wang, Yi; Yu, Zhi-Xiang

    2015-08-18

    Practical syntheses of natural products and their analogues with eight-membered carbocyclic skeletons are important for medicinal and biological investigations. However, methods and strategies to construct the eight-membered carbocycles are limited. Therefore, developing new methods to synthesize the eight-membered carbocycles is highly desired. In this Account, we describe our development of three rhodium-catalyzed cycloadditions for the construction of the eight-membered carbocycles, which have great potential in addressing the challenges in the synthesis of medium-sized ring systems. The first reaction described in this Account is our computationally designed rhodium-catalyzed two-component [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and CO for the diastereoselective construction of bi- and tricyclic cyclooctenones. The design of this reaction is based on the hypothesis that the C(sp(3))-C(sp(3)) reductive elimination of the eight-membered rhodacycle intermediate generated from the rhodium-catalyzed cyclopropane cleavage and alkene insertion, giving Wender's [5 + 2] cycloadduct, is not easy. Under CO atmosphere, CO insertion may occur rapidly, converting the eight-membered rhodacycle into a nine-membered rhodacycle, which then undergoes an easy C(sp(2))-C(sp(3)) reductive elimination process and furnishes the [5 + 2 + 1] product. This hypothesis was supported by our preliminary DFT studies and also served as inspiration for the development of two [7 + 1] cycloadditions: the [7 + 1] cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs) and CO for the construction of cyclooctadienones, and the benzo/[7 + 1] cycloaddition of cyclopropyl-benzocyclobutenes (CP-BCBs) and CO to synthesize the benzocyclooctenones. The efficiency of these rhodium-catalyzed cycloadditions can be revealed by the application in natural product synthesis. Two eight-membered ring-containing natural products, (±)-asterisca-3(15),6-diene and (+)-asteriscanolide, have been

  10. Effect of water and alkali modifications on ETS-10 for the cycloaddition of CO2 to propylene oxide.

    PubMed

    Doskocil, Eric J

    2005-02-17

    Sodium oxide (NaOx) impregnated Engelhard Titanosilicate-10 (ETS-10) molecular sieve catalysts were prepared to enhance the basicity associated with ETS-10 and subsequently investigated for the cycloaddition of carbon dioxide to propylene oxide to produce propylene carbonate. For dry NaOx-modified ETS-10 catalysts that contained no adsorbed water, a maximum yield of propylene carbonate was achieved at a loading of 2.0 excess NaOx species per unit cell. However, the greatest enhancements in the rate of reaction were observed when small amounts of water were adsorbed onto the unmodified ETS-10 catalyst immediately prior to reaction. Surface-bound water appears to enhance the surface Bronsted acidity of the unmodified ETS-10 catalyst via the formation of surface -OH groups at lower water loadings, producing a surface of better-tuned acid-base bifunctional characteristics for the cycloaddition reaction. At levels of hydration greater than 12.5% by mass, the yield of propylene carbonate was further enhanced, but at a smaller rate than that observed at lower rehydration levels, which is more indicative of an enhanced transport effect. Adsorption microcalorimetry of carbon dioxide indicated that, at loadings less than 2.0 NaOx per unit cell, the total uptake of the CO2 adsorption sites required for the reaction were less than in the parent ETS-10 material. However, at higher levels of NaOx occlusion, where the total uptake and strength of the adsorption sites exceeded those observed for the as-received ETS-10 material, the cycloaddition activity of this catalyst suffered due to the reduced pore volume and surface area. It appears that precise tuning of both the surface acidity and basicity is crucial in creating an effective acid-base bifunctional ETS-10 catalyst for the cycloaddition reaction investigated.

  11. Undergraduate Organic Experiment: Tetrazole Formation by Microwave Heated (3 + 2) Cycloaddition in Aqueous Solution

    ERIC Educational Resources Information Center

    DeFrancesco, Heather; Dudley, Joshua; Coca, Adiel

    2018-01-01

    An undergraduate experiment for the organic laboratory is described that utilizes microwave heating to prepare 5- substituted 1H-tetrazole derivatives through a (3 + 2) cycloaddition between aryl nitriles and sodium azide. The reaction mixture is analyzed by thin layer chromatography. The products are purified through an acid-base extraction and…

  12. Theoretical study of Diels-Alder cycloadditions of butadiene to C{sub 70}. An insight into the chemical reactivity of C{sub 70} as compared to C{sub 60}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mestres, J.; Duran, M.; Sola, M.

    1996-05-02

    The eight unique Diels-Alder cycloadditions of butadiene to C{sub 70} are analyzed theoretically and compared with the well-established, two possible Diels-Alder cycloadditions of butadiene to C{sub 60}. Full geometry optimizations of reactants, adducts, and transition states are performed using the AMI semiempirical method followed by single-point ab initio energy calculations. The results show that the cycloaddition of butadiene to the C{sub 70} fullerene in the gas phase is slightly more reactive than that to C{sub 60}. However, in toluene solution calculations yield that the different solvent effects on C{sub 60} and C{sub 70} cause a significant decrease of the energymore » barrier in the C{sub 60} cycloaddition, thus predicting a larger reactivity for C{sub 60} as compared to the C{sub 70} fullerene. 36 refs., 2 figs., 3 tabs.« less

  13. Reverse the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition.

    PubMed

    Turlington, Mark; Pu, Lin

    2011-08-19

    It is discovered that the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition of chiral enynes can be reversed to generate the trans diastereomer as the major product in the absence of a chelate phosphine ligand when the substrate contains an appropriate functional group capable of chelate coordination to the Rh(I) center. This expands the application of the Rh(I)-based catalytic processes to prepare both the cis and trans stereoisomers. © 2011 American Chemical Society

  14. The rearrangements of naphthylnitrenes: UV/Vis and IR spectra of azirines, cyclic ketenimines, and cyclic nitrile ylides.

    PubMed

    Maltsev, Alexander; Bally, Thomas; Tsao, Meng-Lin; Platz, Matthew S; Kuhn, Arvid; Vosswinkel, Michael; Wentrup, Curt

    2004-01-14

    Ar matrix photolysis of 1- and 2-naphthyl azides 3 and 4 at 313 nm initially affords the singlet naphthyl nitrenes, (1)()1 and (1)()2. Relaxation to the corresponding lower energy, persistent triplet nitrenes (3)()1 and (3)()2 competes with cyclization to the azirines 15 and 18, which can also be formed photochemically from the triplet nitrenes. On prolonged irradiation, the azirines can be converted to the seven-membered cyclic ketenimines 10 and 13, respectively, as described earlier by Dunkin and Thomson. However, instead of the o-quinoid ketenimines 16 and 19, which are the expected primary ring-opening products of azirines 15 and 18, respectively, we observed their novel bond-shift isomers 17 and 20, which may be formally regarded as cyclic nitrile ylides. The existence of such ylidic heterocumulenes has been predicted previously, but this work provides the first experimental observation of such species. The factors which are responsible for the special stability of the ylidic species 17 and 20 are discussed.

  15. Tetrazine-Based Cycloadditions: Application to Pretargeted Live Cell Imaging

    PubMed Central

    Devaraj, Neal K.; Weissleder, Ralph; Hilderbrand, Scott A.

    2009-01-01

    Bioorthogonal tetrazine cycloadditions have been applied to live cell labeling. Tetrazines react irreversibly with the strained dienophile norbornene forming dihydropyrazine products and dinitrogen. The reaction is high yielding, selective, and fast in aqueous media. Her2/neu receptors on live human breast cancer cells were targeted with a monoclonal antibody modified with a norbornene. Tetrazines conjugated to a near-infrared fluorochrome selectively and rapidly label the pretargeted antibody in the presence of serum. These findings indicate that this chemistry is suitable for in vitro labeling experiments, and suggests that it may prove a useful strategy for in vivo pretargeted imaging under numerous modalities. PMID:19053305

  16. Computational Studies on the Synthesis of β-Lactams via [2+2] Thermal Cycloadditions

    NASA Astrophysics Data System (ADS)

    Arrieta, Ana; Lecea, Begoña; Cossío, Fernando P.

    The main computational studies on the formation of β-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding β-lactam by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [π2s + (π2s + π2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism.

  17. 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…

  18. Copper(II)-catalyzed oxidative [3+2] cycloaddition reactions of secondary amines with α-diazo compounds: a facile and efficient synthesis of 1,2,3-triazoles.

    PubMed

    Li, Yi-Jin; Li, Xue; Zhang, Shao-Xiao; Zhao, Yu-Long; Liu, Qun

    2015-07-25

    A novel copper-catalyzed [3+2] cycloaddition reaction of secondary amines with α-diazo compounds has been developed via a cross-dehydrogenative coupling process. The reaction involves a sequential aerobic oxidation/[3+2] cycloaddition/oxidative aromatization procedure and provides an efficient method for the construction of 1,2,3-triazoles in a single step in an atom-economic manner from readily available starting materials under very mild conditions.

  19. Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies.

    PubMed

    Haraburda, Ewelina; Torres, Óscar; Parella, Teodor; Solà, Miquel; Pla-Quintana, Anna

    2014-04-22

    Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Dehydrogenative [2 + 2 + 2] Cycloaddition of Cyano-yne-allene Substrates: Convenient Access to 2,6-Naphthyridine Scaffolds.

    PubMed

    Haraburda, Ewelina; Lledó, Agustí; Roglans, Anna; Pla-Quintana, Anna

    2015-06-19

    A rhodium-catalyzed [2 + 2 + 2] cycloaddition of cyano-yne-allene scaffolds followed by a dehydrogenative process enabling the direct synthesis of unsaturated pyridine-containing compounds that can be conveniently converted to 2,6-naphthyridine derivatives is reported.

  1. Computational Prediction of One-Step Synthesis of Seven-membered Fused Rings by (5+2) Cycloaddition Utilising Cycloalkenes

    NASA Astrophysics Data System (ADS)

    Zhou, Chen-Chen; Ke, Xiao-Na; Xu, Xiu-Fang

    2015-07-01

    The (5+2) cycloaddition reaction utilising cycloalkenes is rare, although it is one of the most efficient methods of constructing seven-membered fused rings because of its high atom- and step-economy. In this study, we used quantum mechanical calculations to predict the plausibility of using the Rh-catalysed intermolecular (5+2) cycloaddition of 3-acyloxy-1,4-enynes and cycloalkenes to produce fused seven-membered carbocycles. The calculation results suggest a convenient, highly efficient and energetically practical approach. Strained cycloalkenes, such as cyclopropene, have been predicted to be active, and the desired bicyclic product should be favoured, accompanied by the formation of byproducts from rearrangement reactions. The energy barriers of the alkene insertion step were analysed by the distortion/interaction model to disclose the origins of the different reactivities of cycloalkenes with different ring sizes.

  2. One-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo-[3,4-c]pyrrole]-tetraones and evaluation of their antimycobacterial activity and inhibition of AChE.

    PubMed

    Bharkavi, Chelliah; Vivek Kumar, Sundaravel; Ashraf Ali, Mohamed; Osman, Hasnah; Muthusubramanian, Shanmugam; Perumal, Subbu

    2017-07-15

    An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC 50 1.30µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC 50 value of 0.78±0.01µmol/L. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The divergent synthesis of nitrogen heterocycles by rhodium(II)-catalyzed cycloadditions of 1-sulfonyl 1,2,3-triazoles with 1,3-dienes.

    PubMed

    Shang, Hai; Wang, Yuanhao; Tian, Yu; Feng, Juan; Tang, Yefeng

    2014-05-26

    The first rhodium(II)-catalyzed aza-[4+3] cycloadditions of 1-sulfonyl 1,2,3-triazoles with 1,3-dienes have been developed, and enable the efficient synthesis of highly functionalized 2,5-dihydroazepines from readily available precursors. In some cases, the reaction pathway could divert to formal aza-[3+2] cycloadditions, thus leading to 2,3-dihydropyrroles. In this context, the titled reaction represents a capable tool for the divergent synthesis of two types of synthetically valuable aza-heterocycles from common rhodium(II) iminocarbene intermediates. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. New indolizines with phenanthroline skeleton: Synthesis, structure, antimycobacterial and anticancer evaluation.

    PubMed

    Danac, Ramona; Al Matarneh, Cristina M; Shova, Sergiu; Daniloaia, Teofil; Balan, Mihaela; Mangalagiu, Ionel I

    2015-05-15

    We report herein a feasible study concerning the design, synthesis, structure and in vitro antimycobacterial and anticancer activity of two new classes (containing four and five fused rings) of indolizine with phenanthroline skeleton. The preparation is straight and efficient, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to alkynes or alkenes dipolarophiles. The cycloaddition reactions are highly stereo- or regioselective, according with the dipolarophiles nature. The structure of the new compounds was assigned unambiguously, X-ray analysis including. The primary antimycobacterial screening reveals that one of the thirteen tested compounds had a good activity against Mycobacterium tuberculosis H37Rv under aerobic conditions. The antiproliferative evaluation against a NCI 60 human tumor cell line panel, revealed that two indolizine with phenanthroline skeleton exhibit a selective and significant antitumor growth inhibitory activity against Breast Cancer (MCF7 and T-47D) and a slightly moderate activity against some forms of Leukemia, Non-Small Cell Lung Cancer, Renal Cancer and Breast Cancer (MDA-MB-468). The X-ray diffraction study of the indolizines with phenanthroline skeleton prove a flat coplanar structure which, corroborated with their anticancer activity, allow us to suggest that an interaction with DNA (via an intercalation mechanism) would be reasonable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition of 1-yne/ene-vinylcyclopropanes and CO: homologous Pauson-Khand reaction and total synthesis of (+/-)-alpha-agarofuran.

    PubMed

    Jiao, Lei; Lin, Mu; Zhuo, Lian-Gang; Yu, Zhi-Xiang

    2010-06-04

    A novel Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition, which can be regarded as a homologous Pauson-Khand reaction, was developed to synthesize bicyclic cyclohexenones and cyclohexanones, enabling a new approach for synthesis of six-membered carbocycles ubiquitously found in natural products and pharmaceutics. The significance of the Rh-catalyzed [(3 + 2) + 1] cycloaddition has been demonstrated by the total synthesis of a furanoid sesquiterpene natural product, alpha-agarofuran, in which the bicyclic skeleton was constructed by the [(3 + 2) + 1] reaction of 1-yne-VCP and CO.

  6. Mild and modular surface modification of cellulose via hetero Diels-Alder (HDA) cycloaddition.

    PubMed

    Goldmann, Anja S; Tischer, Thomas; Barner, Leonie; Bruns, Michael; Barner-Kowollik, Christopher

    2011-04-11

    A combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and hetero Diels-Alder (HDA) cycloaddition was used to effect, under mild (T ≈ 20 °C), fast, and modular conditions, the grafting of poly(isobornyl acrylate) (M(n) = 9800 g mol(-1), PDI = 1.19) onto a solid cellulose substrate. The active hydroxyl groups expressed on the cellulose fibers were converted to tosylate leaving groups, which were subsequently substituted by a highly reactive cyclopentadienyl functionality (Cp). By employing the reactive Cp-functionality as a diene, thiocarbonyl thio-capped poly(isobornyl acrylate) synthesized via RAFT polymerization (mediated by benzyl pyridine-2-yldithioformiate (BPDF)) was attached to the surface under ambient conditions by an HDA cycloaddition (reaction time: 15 h). The surface-modified cellulose samples were analyzed in-depth by X-ray photoelectron spectroscopy, scanning electron microscopy, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy as well as Fourier transform infrared microscopy employing a focal plane array detector for imaging purposes. The analytical results provide strong evidence that the reaction of suitable dienophiles with Cp-functional cellulose proceeds under mild reaction conditions (T ≈ 20 °C) in an efficient fashion. In particular, the visualization of individual modified cellulose fibers via high-resolution FT-IR microscopy corroborates the homogeneous distribution of the polymer film on the cellulose fibers.

  7. Palladium complexes of a phosphorus ylide with two stabilizing groups: synthesis, structure, and DFT study of the bonding modes.

    PubMed

    Falvello, Larry R; Ginés, Juan Carlos; Carbó, Jorge J; Lledós, Agustí; Navarro, Rafael; Soler, Tatiana; Urriolabeitia, Esteban P

    2006-08-21

    The phosphorus ylide ligand [Ph3P=C(CO2Me)C(=NPh)CO2Me] (L1) has been prepared and fully characterized by spectroscopic, crystallographic, and density functional theory (DFT) methods (B3LYP level). The reactivity of L1 toward several cationic Pd(II) and Pt(II) precursors, with two vacant coordination sites, has been studied. The reaction of [M(C/\\X)(THF)2]ClO4 with L1 (1:1 molar ratio) gives [M(C/\\X)(L1)]ClO4 [M = Pd, C/\\X = C6H4CH2NMe2 (1), S-C6H4C(H)MeNMe2 (2), CH2-8-C9H6N (3), C6H4-2-NC5H4 (4), o-CH2C6H4P(o-tol)2 (6), eta3-C3H5 (7); M = Pt, C/\\X = o-CH2C6H4P(o-tol)2 (5); M(C/\\X) = Pd(C6F5)(SC4H8) (8), PdCl2 (9)]. In complexes 1-9, the ligand L1 bonds systematically to the metal center through the iminic N and the carbonyl O of the stabilizing CO2Me group, as is evident from the NMR data and from the X-ray structure of 3. Ligand L1 can also be orthopalladated by reaction with Pd(OAc)2 and LiCl, giving the dinuclear derivative [Pd(mu-Cl)(C6H4-2-PPh2=C(CO2Me)C(CO2Me)=NPh)]2 (10). The X-ray crystal structure of 10 is also reported. In none of the prepared complexes 1-10 was the C(alpha) atom found to be bonded to the metal center. DFT calculations and Bader analysis were performed on ylide L1 and complex 9 and its congeners in order to assess the preference of the six-membered N,O metallacycle over the four-membered C,N and five-membered C,O rings. The presence of two stabilizing groups at the ylidic C causes a reduction of its bonding capabilities. The increasing strength of the Pd-C, Pd-O, and Pd-N bonds along with other subtle effects are responsible for the relative stabilities of the different bonding modes.

  8. 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.

  9. 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…

  10. Novel quinazoline ring synthesis by cycloaddition of N-arylketenimines with N,N-disubstituted cyanamides.

    PubMed

    Shimizu, Masao; Oishi, Akihiro; Taguchi, Yoichi; Gama, Yasuo; Shibuya, Isao

    2002-03-01

    The reaction of N-aryl-substituted ketenimines with N,N-disubstituted cyanamides or (MeS)2C=N-CN under high pressure afforded 4-(N,N-disubstituted amino) or 4-(MeS)2C=N-substituted quinazoline derivatives, respectively. These products were formed by [4+2] cycloaddition between the aza-diene moieties of the N-arylsubstituted ketenimines and cyano groups. A 4-(unsubstituted amino)quinazoline derivative was synthesized by hydrolysis of the latter product.

  11. Stepwise cycloaddition reaction of N-phenacylbenzothiazolium bromides and nitroalkenes for tetrahydro-, dihydro- and benzo[d]pyrrolo[2,1-b]thiazoles

    NASA Astrophysics Data System (ADS)

    Jin, Gong; Sun, Jing; Yang, Ren-Yin; Yan, Chao-Guo

    2017-04-01

    The triethylamine promoted stepwise 1,3-dipolar cycloaddition reaction of N-phenacylbenzothiazolium bromides with nitroalkenes in ethanol resulted in a mixture of two isomeric tetrahydrobenzo[d]pyrrolo[2,1-b]thiazoles with cis/trans/cis- and all-trans-configurations. More importantly, the corresponding dihydrobenzo[d]pyrrolo[2,1-b]thiazoles can be selectively prepared in refluxing ethanol and the benzo[d]pyrrolo[2,1-b]thiazoles can be obtained in satisfactory yields by sequential dehydrogenation with DDQ as oxidizer. On the other hand, the similar cycloaddition reaction of N-phenacylbenzothiazolium bromides with 1-methy-1-nitroalkenes in refluxing ethanol afforded benzo[d]pyrrolo[2,1-b]thiazoles with splitting out of nitro group. The stereochemistry of the spiro compounds was clearly elucidated on the basis of NMR spectra and sixteen single crystal structures.

  12. Synthesis of Functionalized Pyrazoles via 1,3-Dipolar Cycloaddition of α-Diazo-β-ketophosphonates, Sufones and Esters with Electron-Deficient Alkenes.

    PubMed

    Baiju, T V; Namboothiri, Irishi N N

    2017-10-01

    1,3-Dipolar cycloaddition of diazo compounds with olefinic substrates is a promising atom-economic strategy for the construction of functionalized pyrazoles. Over the last few years, our group has been engaged in the synthesis of phosphonyl/sulfonylpyrazoles and pyrazole esters by employing Bestmann-Ohira Reagent (BOR) and its sulfur and ester analogs as 1,3-dipole precursors with various dipolarophiles. This account describes the novel synthetic methods developed in our laboratory, in the perspective of closely related work by others, for the synthesis of phosphonyl/sulfonylpyrazoles, pyrazole esters and the total synthesis of Withasomnine, a natural product, by using 1,3-dipolar cycloaddition as the key step. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Ultrasound and microwave assisted synthesis of isoindolo-1,2-diazine: a comparative study.

    PubMed

    Bejan, Vasilichia; Mantu, Dorina; Mangalagiu, Ionel I

    2012-09-01

    A comparative study, ultrasound (US) versus microwave (MW) versus conventional thermal heating (TH), for synthesis of isoindolo-1,2-diazine is described. The reaction pathway is fast, efficient and straight applicable, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to 1,4-naphthoquinone. A feasible reaction mechanism for the obtaining of the fully aromatized tetra- and penta- cyclic isoindolo-1,2-diazine is presented. Under US irradiation the yields are much higher (sometimes substantially, by almost double), the reaction time decreases substantially, the reaction conditions are milder. The use of a generator with a higher nominal power induces higher yields and short reaction times. Overall the use of US it proved to be more efficient than MW or TH. A feasible explication for US efficiency is presented. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Enantioselective synthesis of C2 -symmetric spirobipyridine ligands through cationic Rh(I)/modified-BINAP- catalyzed double [2 + 2 + 2] cycloaddition.

    PubMed

    Wada, Azusa; Noguchi, Keiichi; Hirano, Masao; Tanaka, Ken

    2007-03-29

    [structure: see text]. Enantioenriched C2-symmetric spirobipyridine ligands were efficiently synthesized through a cationic rhodium(I)/(R)-Segphos or (R)-H8-BINAP complex-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition of bis-diynenitriles.

  15. The structure of SpnF a standalone enzyme that catalyzes [4 + 2] cycloaddition

    DOE PAGES

    Fage, Christopher D.; Isiorho, Eta A.; Liu, Yungnan; ...

    2015-03-02

    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, in this paper we determined the 1.50-Å-resolution crystal structure of SpnF bound to S-adenosylhomocysteine. Finally, this sets the stage for advanced experimental and computational studies to determine the precise mechanism of SpnF-mediated cyclization.

  16. The discovery of [Ni(NHC)RCN]2 species and their role as cycloaddition catalysts for the formation of pyridines.

    PubMed

    Stolley, Ryan M; Duong, Hung A; Thomas, David R; Louie, Janis

    2012-09-12

    The reaction of Ni(COD)(2), IPr, and nitrile affords dimeric [Ni(IPr)RCN](2) in high yields. X-ray analysis revealed these species display simultaneous η(1)- and η(2)-nitrile binding modes. These dimers are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. Kinetic analysis showed the reaction to be first order in [Ni(IPr)RCN](2), zeroth order in added IPr, zeroth order in nitrile, and zeroth order in diyne. Extensive stoichiometric competition studies were performed, and selective incorporation of the exogenous, not dimer bound, nitrile was observed. Post cycloaddition, the dimeric state was found to be largely preserved. Nitrile and ligand exchange experiments were performed and found to be inoperative in the catalytic cycle. These observations suggest a mechanism whereby the catalyst is activated by partial dimer-opening followed by binding of exogenous nitrile and subsequent oxidative heterocoupling.

  17. The Discovery of [Ni(NHC)RCN]2 Species and their Role as Cycloaddition Catalysts for the Formation of Pyridines

    PubMed Central

    Stolley, Ryan M.; Duong, Hung A.; Thomas, David R.; Louie, Janis

    2012-01-01

    The reaction of Ni(COD)2, IPr, and nitrile affords dimeric [Ni(IPr)RCN]2 in high yields. X-ray analysis revealed these species display simultaneous η1- and η2-nitrile binding modes. These dimers are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. Kinetic analysis showed the reaction to be first order in [Ni(IPr)RCN]2, zeroth order in added IPr, zeroth order in nitrile, and zeroth order in diyne. Extensive stoichiometric competition studies were performed, and selective incorporation of the exogenous, not dimer bound, nitrile was observed. Post cycloaddition, the dimeric state was found to be largely preserved. Nitrile and ligand exchange experiments were performed and found to be inoperative in the catalytic cycle. These observations suggest a mechanism whereby the catalyst is activated by partial dimer-opening followed by binding of exogenous nitrile and subsequent oxidative heterocoupling. PMID:22917161

  18. Photochemical cycloaddition reagents for rigidly attaching the 1, 4-dimethoxynaphthalene chromophore to scaffold alkenes

    PubMed

    Margetic; Russell; Warrener

    2000-12-14

    The norbornanecyclobutene epoxides 1a-1c containing a fused 1, 4-dimethoxynaphthalene chromophore have been reacted with cyclobutenes, cyclohexenes, norbornenes, 7-isopropylidenenorbornenes, 7-azanorbornenes, and other cyclic or electron-deficient alkenes at room temperature to form 1:1 adducts in stereoselective 1,3-dipolar cycloaddition reactions; alkynes can also participate in this reaction. The ability to form 2:1 adducts has also been demonstrated, thereby opening up opportunities for preparing functionalized products with large chromophore separations.

  19. Construction of Benzene Rings by Copper-Catalyzed Cycloaddition Reactions of Oximes and Maleimides: An Access to Fused Phthalimides.

    PubMed

    Yang, Jie; Zhao, Bo; Xi, Yue; Sun, Si; Yang, Zhen; Ye, Ying; Jiang, Kun; Wei, Ye

    2018-02-16

    A useful Cu-catalyzed cycloaddition protocol for the construction of benzene rings has been achieved. The reactions, utilizing readily available oximes and maleimides as starting materials, proceed under mild reaction conditions to generate a series of structurally interesting fused-phthalimides that are difficult to be prepared by conventional methods.

  20. The Use of Nitrone Cycloadditions in the Synthesis of Beta-Amino Aldehydes and Unsaturated Amines.

    DTIC Science & Technology

    1986-01-01

    with alkenes (dipolarophiles) to produce isoxazolidines (2) in a fashion similar to the (4+2] Diels - Alder reaction.’ The cycloaddition results in...structures to study enzyme inhibition, and they serve as useful intermediates in the synthesis of $-lactams. 3 3 Table IV summarizes attempts to oxidize p...84% yield (Table V, entry 3). Due to the mechanistic imperative, acid catalyzed elimination always yielded the allylic amine in which the alkene

  1. Catalytic asymmetric enyne addition to aldehdyes and Rh(I)-catalyzed stereoselective domino Pauson-Khand/[4 + 2] cycloaddition.

    PubMed

    Chen, Wei; Tay, Jia-Hui; Ying, Jun; Yu, Xiao-Qi; Pu, Lin

    2013-03-15

    The 1,1'-bi-2-naphthol-ZnEt2-Ti(O(i)Pr)4-Cy2NH system is found to catalyze the 1,3-enyne addition to aliphatic aldehydes as well as other aldehydes at room temperature with 75-96% yield and 82-97% ee. This system is also broadly applicable for the highly enantioselective reaction of other alkyl-, aryl-, and silylalkynes with structurally diverse aldehydes. The propargylic alcohols prepared from the catalytic asymmetric enyne addition to aliphatic aldehydes are used to prepare a series of optically active trienynes. In the presence of a catalytic amount of [RhCl(CO)2]2 and 1 atm of CO, the optically active trienynes undergo highly stereoselective domino Pauson-Khand/[4 + 2] cycloaddition to generate optically active multicyclic products. The Rh(I) catalyst is also found to catalyze the coupling of a diyne with CO followed by [4 + 2] cycloaddition to generate an optically active multicyclic product. These transformations are potentially useful for the asymmetric synthesis of polyquinanes containing a quaternary chiral carbon center.

  2. Causation in a Cascade: The Origins of Selectivities in Intramolecular Nitrone Cycloadditions

    PubMed Central

    Krenske, Elizabeth H.; Agopcan, Sesil; Aviyente, Viktorya; Houk, K. N.; Johnson, Brian A.; Holmes, Andrew B.

    2012-01-01

    The factors controlling chemo-, regio-, and stereoselectivity in a cascade of reactions starting from a bis(cyanoalkenyl)oxime and proceeding via nitrone cycloadditions, have been unravelled through a series of density functional calculations with several different functionals. Both kinetic and thermodynamic control of the reaction cascade are important depending upon conditions. Kinetic control is analysed by the distortion/interaction model and is found to be dictated by differences in distortions of the cycloaddends in the transition states. A new mechanism competing with that originally proposed in the application of these reactions to the histrionicotoxin synthesis is discovered in these studies. PMID:22788115

  3. Approaches to the synthesis of (+/-)-strychnine via the cobalt-mediated [2 + 2 + 2] cycloaddition: rapid assembly of a classic framework.

    PubMed

    Eichberg, M J; Dorta, R L; Grotjahn, D B; Lamottke, K; Schmidt, M; Vollhardt, K P

    2001-09-26

    Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.

  4. Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions.

    PubMed

    Friscourt, Frédéric; Fahrni, Christoph J; Boons, Geert-Jan

    2015-09-28

    Fluorogenic reactions, in which non- or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl-DIBO) can undergo fast strain-promoted cycloaddition reactions under catalyst-free conditions with azides, nitrones, nitrile oxides, as well as mono- and disubstituted diazo-derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited an approximately 160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions

    PubMed Central

    Friscourt, Frédéric; Fahrni, Christoph J.; Boons, Geert-Jan

    2016-01-01

    Fluorogenic reactions in which non- or weakly-fluorescent reagents produce highly fluorescent products are attractive for detecting a broad range of compounds in the fields of bio-conjugation and material sciences. We report here that Fl-DIBO, a dibenzocyclooctyne derivative modified with a cyclopropenone moiety, can undergo fast strain-promoted cycloadditions under catalyst-free conditions with azides, nitrones, nitrile oxides as well as mono- and disubstituted diazo-derivatives. While the reaction with nitrile oxides, nitrones and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited a ~160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules and the studies presented here demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. PMID:26330090

  6. Site-Specific Antibody Labeling by Covalent Photoconjugation of Z Domains Functionalized for Alkyne-Azide Cycloaddition Reactions.

    PubMed

    Perols, Anna; Arcos Famme, Melina; Eriksson Karlström, Amelie

    2015-11-01

    Antibodies are extensively used in research, diagnostics, and therapy, and for many applications the antibodies need to be labeled. Labeling is typically performed by using amine-reactive probes that target surface-exposed lysine residues, resulting in heterogeneously labeled antibodies. An alternative labeling strategy is based on the immunoglobulin G (IgG)-binding protein domain Z, which binds to the Fc region of IgG. Introducing the photoactivable amino acid benzoylphenylalanine (BPA) into the Z domain makes it possible for a covalent bond to be be formed between the Z domain and the antibody on UV irradiation, to produce a site-specifically labeled product. Z32 BPA was synthesized by solid-phase peptide synthesis and further functionalized to give alkyne-Z32 BPA and azide-Z32 BPA for Cu(I) -catalyzed cycloaddition, as well as DBCO-Z32 BPA for Cu-free strain-promoted cycloaddition. The Z32 BPA variants were conjugated to the human IgG1 antibody trastuzumab and site-specifically labeled with biotin or fluorescein. The fluorescently labeled trastuzumab showed specific staining of the membranes of HER2-expressing cells in immunofluorescence microscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [2+2] cycloaddition of 1,3-dienes by visible light photocatalysis.

    PubMed

    Hurtley, Anna E; Lu, Zhan; Yoon, Tehshik P

    2014-08-18

    [2+2] photocycloadditions of 1,3-dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3-dienes. The ability to use long-wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high-energy UVC radiation required for direct photoexcitation of 1,3-dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Efficient assembly of polysubstituted pyrroles via a (3 + 2) cycloaddition/skeletal rearrangement/redox isomerization cascade reaction.

    PubMed

    Yu, Yuanyuan; Wang, Chunyu; He, Xinze; Yao, Xiaotong; Zu, Liansuo

    2014-07-03

    An unprecedented cascade strategy, used in conjunction with a redox isomerization, for the synthesis of 3-allyl pyrroles is reported. In a single step, readily accessible simple starting materials are transformed into highly substituted pyrroles with high efficiency. The products obtained contain allyl substituents, which can be readily elaborated to other useful functional groups. The reaction proceeds through an unusual (3 + 2) cycloaddition/skeletal rearrangement/redox isomerization pathway.

  9. Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach.

    PubMed

    Gao, Ping; Sun, Lin; Zhou, Junsu; Li, Xiao; Zhan, Peng; Liu, Xinyong

    2016-09-01

    In recent years, a variety of new synthetic methodologies and concepts have been proposed in the search for new pharmaceutical lead structures and optimization. Notably, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry approach has drawn great attention and has become a powerful tool for the generation of privileged medicinal skeletons in the discovery of anti-HIV agents. This is due to the high degree of reliability, complete specificity (chemoselectivity and regioselectivity), mild conditions, and the biocompatibility of the reactants. Herein, the authors describe the progress thus far on the discovery of novel anti-HIV agents via the CuAAC click chemistry-based approach. CuAAC click chemistry is a proven protocol for synthesizing triazole products which could serve as basic pharmacophores, act as replacements of traditional scaffold or substituent modification, be a linker of dual-target or dual-site inhibitors and more for the discovery of novel anti-HIV agents. What's more, it also provides convenience and feasibility for dynamic combinatorial chemistry and in situ screening. It is envisioned that click chemistry will draw more attention and make more contributions in anti-HIV drug discovery in the future.

  10. 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.

  11. Coordinative Alignment of Chiral Molecules to Control over the Chirality Transfer in Spontaneous Resolution and Asymmetric Catalysis.

    PubMed

    Xia, Zhengqiang; Jing, Xu; He, Cheng; Wang, Xiaoge; Duan, Chunying

    2017-11-13

    The production and availability of enantiomerically pure compounds that spurred the development of chiral technologies and materials are very important to the fine chemicals and pharmaceutical industries. By coordinative alignment of enantiopure guests in the metal‒organic frameworks, we reported an approach to control over the chirality of homochiral crystallization and asymmetric transformation. Synthesized by achiral triphenylamine derivatives, the chirality of silver frameworks was determined by the encapsulated enantiopure azomethine ylides, from which clear interaction patterns were observed to explore the chiral induction principles. With the changing of addition sequence of substrates, the enantioselectivity of asymmetric cycloaddition was controlled to verify the determinant on the chirality of the bulky MOF materials. The economical chirality amplification that merges a series of complicated self-inductions, bulk homochiral crystallization and enantioselective catalysis opens new avenues for enantiopure chemical synthesis and provides a promising path for the directional design and development of homochiral materials.

  12. Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes.

    PubMed

    Martin, David B C; Nguyen, Lucas Q; Vanderwal, Christopher D

    2012-01-06

    A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.

  13. [3 + 2] Cycloaddition reactions of thioisatin with thiazolidine-2-carboxylic acid: a versatile route to new heterocyclic scaffolds

    PubMed Central

    2011-01-01

    A facile synthesis of azabicycloadducts is described by 1,3-dipolar cycloaddition reactions of thioisatin with thiazolidine-2-carboxylic acid in the presence of various electron rich and electron deficient dipolarophiles. Theoritical calculations have been performed to study the regioselectivity of products. The geometrical and energetic properties have been analyzed for the different reactants, transition states and cycloadducts formed. PMID:22373364

  14. One-pot, two-step synthesis of imidazo[1,2-a]benzimidazoles via a multicomponent [4 + 1] cycloaddition reaction.

    PubMed

    Hsiao, Ya-Shan; Narhe, Bharat D; Chang, Ying-Sheng; Sun, Chung-Ming

    2013-10-14

    A one-pot, two-step synthesis of imidazo[1,2-a]benzimidazoles has been achieved by a three-component reaction of 2-aminobenzimidazoles with an aromatic aldehyde and an isocyanide. The reaction involving condensation of 2-aminobenzimidazole with an aldehyde is run under microwave activation to generate an imine intermediate under basic conditions which then undergoes [4 + 1] cycloaddition with an isocyanide.

  15. Ferrocene Derived Bifunctional Phosphine-Catalyzed Asymmetric Oxa-[4+2] Cycloaddition of α-Substituted Allenones with Enones.

    PubMed

    Wang, Huamin; Lu, Weike; Zhang, Junliang

    2017-10-04

    An efficient ferrocene-derived bifunctional phosphine-catalyzed enantioselective oxa-[4+2] cycloaddition of α-substituted allenones with a broad range of enones is investigated for the preparation of stereodefined dihydropyrans in good to excellent yields (up to 99 %) and excellent enantioselectivity (up to 99 % ee). Furthermore, a series of valuable chiral polyheterocyclic frameworks can be efficiently achieved in good yields with excellent enantioselectivities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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

  17. 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

  18. Highly regioselective Lewis acid-catalyzed [3+2] cycloaddition of alkynes with donor-acceptor oxiranes by selective carbon-carbon bond cleavage of epoxides.

    PubMed

    Liu, Renrong; Zhang, Mei; Zhang, Junliang

    2011-12-28

    A novel, efficient, highly regioselective Sc(OTf)(3)-catalyzed [3+2] cycloaddition of electron-rich alkynes with donor-acceptor oxiranes via highly chemoselective C-C bond cleavage under mild conditions was developed. This journal is © The Royal Society of Chemistry 2011

  19. Teaching Experiment to Elucidate a Cation-Pi Effect in an Alkyne Cycloaddition Reaction and Illustrate Hypothesis-Driven Design of Experiments

    ERIC Educational Resources Information Center

    St.Germain, Elijah J.; Horowitz, Andrew S.; Rucco, Dominic; Rezler, Evonne M.; Lepore, Salvatore D.

    2017-01-01

    An organic chemistry experiment is described that is based on recent research to elucidate a novel cation-pi interaction between tetraalkammonium cations and propargyl hydrazines. This nonbonded interaction is a key component of the mechanism of ammonium-catalyzed intramolecular cycloaddition of nitrogen to the terminal carbon of a C-C triple bond…

  20. 1. Progress toward the synthesis of vancosamine using a tandem [4+2]/[3+2] cycloaddition. 2. Discussion boards and pre-lecture quizzes in organic chemistry courses

    NASA Astrophysics Data System (ADS)

    Miller, Tyson A.

    The sugar vancosamine is one of the two sugar residues found on the broad spectrum antibiotic vancomycin. A strategy using a tandem intermolecular [4+2]/intermolecular [3+2] cycloaddition with nitro olefins was employed in an effort to enantioselectively synthesize the target. The [4+2] cycloaddition proceeded well with tin tetrachloride in high yield. However, the products from the [3+2] cycloaddition afforded diastereomers with stereocenters that were inconsistent with the natural product. An online facilitated group work assignment was introduced to a first semester non-majors organic chemistry lecture courses with large enrollments (˜300--660 students). Student opinion surveys, performance scores, and a detailed account of time spent by the facilitator afforded insight on the value of such assignments with large class sizes. Format and number of attempts were varied in online pre-lecture quizzes administered to a first semester non-majors organic chemistry lecture course. Student quiz performance and post-quiz assessment shows significant differences in mastery of material and class preparedness with format and number of attempts. When combined with student survey data, recommendations are made as to how format selection and number of attempts can optimize the value of online pre-lecture quizzes as a learning tool and as an assessment tool.

  1. Cationic 1,2,3-Triazolium Alkynes: Components To Enhance 1,4-Regioselective Azide-Alkyne Cycloaddition Reactions.

    PubMed

    Monasterio, Zaira; Sagartzazu-Aizpurua, Maialen; Miranda, José I; Reyes, Yuri; Aizpurua, Jesus M

    2016-02-19

    4-Alkynyl-1,2,3-triazolium cations undergo thermal [3 + 2] cycloaddition reactions with azides roughly 50- to 100-fold faster than comparable noncharged alkynes. Further, the reaction is highly 1,4-regioselective (dr up to 99:1) owing to the selective stabilization of 1,4-TS transition states via conjugative π-acceptor assistance of the alkyne triazolium ring. The novel cationic triazolium alkynes also accelerate the CuAAC reaction to provide bis(1,2,3-triazoles) in an "ultrafast" way (<5 min).

  2. New spiro-oxindole constructed with pyrrolidine/thioxothiazolidin-4-one derivatives: Regioselective synthesis, X-ray crystal structures, Hirshfeld surface analysis, DFT, docking and antimicrobial studies

    NASA Astrophysics Data System (ADS)

    Barakat, Assem; Soliman, Saied M.; Al-Majid, Abdullah Mohammed; Ali, M.; Islam, Mohammad Shahidul; Elshaier, Yaseen A. M. M.; Ghabbour, Hazem A.

    2018-01-01

    In this work, polycyclic heterocycles containing spirooxindole, pyrrolidine, and thioxothiazolidin-4-one rings have been synthesized via the regioselective 1,3-dipolar cycloaddition of azomethine ylide, which is generated in situ by the condensation of the dicarbonyl compound isatin and the secondary amino acid (L-proline), with 5-arylidine-2-thioxothiazolidin-4-one as the dipolarophile. The structure of the synthesized compounds 4a and 4b were determined by using X-ray single crystal diffraction, and also, Hirshfeld surface analysis were reported. Their geometric parameters were calculated using density functional theory at the B3LYP/6-311G (d,p) level of theory. Both compounds showed antimicrobial and antifungal activity better than selected standards (ampicillin and gentamicin in case of antibacterial activity and Amphotericin A and fluconazole in case of antifungal activity). Molecular docking study of the synthesized compounds indicated that phenyl group plays an important role in determination of compound interaction inside the receptors.

  3. A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities.

    PubMed

    Bharkavi, Chelliah; Vivek Kumar, Sundaravel; Ashraf Ali, Mohamed; Osman, Hasnah; Muthusubramanian, Shanmugam; Perumal, Subbu

    2016-11-15

    A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC 50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC 50 <1.56μM) and 6l (IC 50 =2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC 50 values of 1.10 and 1.16μmol/L respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Cobalt/rhodium heterobimetallic nanoparticle-catalyzed carbonylative [2+2+1] cycloaddition of allenes and bisallenes to Pauson-Khand-type reaction products.

    PubMed

    Park, Ji Hoon; Kim, Eunha; Kim, Hyeong-Mook; Choi, Soo Young; Chung, Young Keun

    2008-05-28

    The first catalytic intra- and intermolecular [2+2+1] cocyclization reactions of allenes and carbon monoxide have been developed. In the Co(2)Rh(2) heterobimetallic nanoparticle-catalyzed carbonylative [2+2+1] cycloaddition of allenes and carbon monoxide, the allenes formally serve both as an excellent alkene- and alkyne-like moiety within a Pauson-Khand-type process.

  5. A Catalytic Asymmetric Synthesis of Polysubstituted Piperidines Using a Rhodium (I) Catalyzed [2+2+2] Cycloaddition Employing a Cleavable Tether

    PubMed Central

    Martin, Timothy J.; Rovis, Tomislav

    2013-01-01

    An enantioselective rhodium (I) catalyzed [2+2+2] cycloaddition with a cleavable tether has been developed. The reaction proceeds with a variety of alkyne substrates in good yield and high enantioselectivity. Upon reduction of the vinylogous amide in high diastereoselectivity (>19:1) and cleavage of the tether, N-methylpiperidine products with functional group handles can be accessed. PMID:23606664

  6. Solid-state polymerisation via [2+2] cycloaddition reaction involving coordination polymers.

    PubMed

    Medishetty, Raghavender; Park, In-Hyeok; Lee, Shim Sung; Vittal, Jagadese J

    2016-03-14

    Highly crystalline metal ions containing organic polymers are potentially useful to manipulate the magnetic and optical properties to make advanced multifunctional materials. However, it is challenging to synthesise monocrystalline metal complexes of organic polymers and single-phase hybrid materials made up of both coordination and organic polymers by traditional solution crystallisation. This requires an entirely different approach in the solid-state by thermal or photo polymerisation of the ligands. Among the photochemical methods available, [2+2] cycloaddition reaction has been recently employed to generate cyclobutane based coordination polymers from the metal complexes. Cyclobutane polymers have also been integrated into coordination polymers in this way. Recent advancements in the construction of polymeric chains of cyclobutane rings through photo-dimerisation reaction in the monocrystalline solids containing metal complexes, coordination polymers and metal-organic framework structures are discussed here.

  7. Functionalized MIL-101 with imidazolium-based ionic liquids for the cycloaddition of CO2 and epoxides under mild condition

    NASA Astrophysics Data System (ADS)

    Liu, Dan; Li, Gang; Liu, Haiou

    2018-01-01

    A kind of multi-functional sites metal-organic framework (MOF) composite (MIL-101-IMBr) was successfully prepared by post-synthesis modification of MIL-101 with imidazolium-based ionic liquids. The ionic liquids not only functionalize as basic sites but also provide halide anions, which serve as a nucleophile in cycloaddition reaction. The prepared functional MOF materials were characterized by X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, N2 adsorption-desorption and CO2 temperature programmed desorption. The results of fourier transform infrared spectroscopy and energy dispersive spectroscopy show that the MIL-101-IMBr composite was successfully synthesized. The N2 adsorption-desorption results clearly demonstrated that the modified composites still preserve high BET surface area and total pore volume. The composite exhibits high catalytic activity for the cycloaddition of CO2 with epoxides under mild and co-catalyst free conditions. The conversion of propylene oxide was 95.8% and the selectivity of cyclic carbonate was 97.6% under 0.8 MPa at 80 °C for 4 h. Moreover, the catalyst can be used for at least five times.

  8. Copper-Catalyzed Sulfonyl Azide-Alkyne Cycloaddition Reactions: Simultaneous Generation and Trapping of Copper-Triazoles and -Ketenimines for the Synthesis of Triazolopyrimidines.

    PubMed

    Nallagangula, Madhu; Namitharan, Kayambu

    2017-07-07

    First simultaneous generation and utilization of both copper-triazole and -ketenimine intermediates in copper-catalyzed sulfonyl azide-alkyne cycloaddition reactions is achieved for the one-pot synthesis of triazolopyrimidines via a novel copper-catalyzed multicomponent cascade of sulfonyl azides, alkynes, and azirines. Significantly, the reaction proceeds under very mild conditions in good yields.

  9. Gold-catalyzed sequential annulations towards 3,4-fused bi/tri-cyclic furans involving a [3+2+2]-cycloaddition.

    PubMed

    Liu, Suna; Yang, Pu; Peng, Shiyong; Zhu, Chenghao; Cao, Shengyu; Li, Jian; Sun, Jiangtao

    2017-01-17

    A gold-catalyzed sequential annulation reaction to prepare 3,4-fused bicyclic furan compounds has been realized by employing 2-(1-alkynyl)-2-alken-1-ones and 1,3,5-triazines as the starting materials under mild reaction conditions. This protocol features multiple bond formation in a single operation with the incorporation of two nitrogen and two carbon atoms into the final products. A mechanistic investigation reveals that the sequential annulations involved an unprecedented stepwise [3+2+2]-cycloaddition.

  10. Reaction of an Iron(IV) Nitrido Complex with Cyclohexadienes: Cycloaddition and Hydrogen-Atom Abstraction

    PubMed Central

    2015-01-01

    The iron(IV) nitrido complex PhB(MesIm)3Fe≡N reacts with 1,3-cyclohexadiene to yield the iron(II) pyrrolide complex PhB(MesIm)3Fe(η5-C4H4N) in high yield. The mechanism of product formation is proposed to involve sequential [4 + 1] cycloaddition and retro Diels–Alder reactions. Surprisingly, reaction with 1,4-cyclohexadiene yields the same iron-containing product, albeit in substantially lower yield. The proposed reaction mechanism, supported by electronic structure calculations, involves hydrogen-atom abstraction from 1,4-cyclohexadiene to provide the cyclohexadienyl radical. This radical is an intermediate in substrate isomerization to 1,3-cyclohexadiene, leading to formation of the pyrrolide product. PMID:25068927

  11. 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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Decreasing Distortion Energies without Strain: Diazo-Selective 1,3-Dipolar Cycloadditions.

    PubMed

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

    2016-07-15

    The diazo group has attributes that complement those of the azido group for applications in chemical biology. Here, we use computational analyses to provide insights into the chemoselectivity of the diazo group in 1,3-dipolar cycloadditions. Dipole distortion energies are responsible for ∼80% of the overall energetic barrier for these reactions. Here, we show that diazo compounds, unlike azides, provide an opportunity to decrease that barrier substantially without introducing strain into the dipolarophile. The ensuing rate enhancement is due to the greater nucleophilic character of a diazo group compared to that of an azido group, which can accommodate decreased distortion energies without predistortion. The tuning of distortion energies with substituents in a diazo compound or dipolarophile can enhance reactivity and selectivity in a predictable manner. Notably, these advantages of diazo groups are amplified in water. Our findings provide a theoretical framework that can guide the design and application of both diazo compounds and azides in "orthogonal" contexts, especially for biological investigations.

  13. An unprecedented chemospecific and stereoselective tandem nucleophilic addition/cycloaddition reaction of nucleophilic carbenes with ketenimines.

    PubMed

    Cheng, Ying; Ma, Yang-Guang; Wang, Xiao-Rong; Mo, Jun-Ming

    2009-01-16

    The first study of the reaction between nucleophilic carbenes and ketenimines is reported. The interaction of thiazole and benzothiazole carbenes with ketenimines proceeded in a chemospecific and stereoselective manner to produce thiazole- and benzothiazole-spiro-pyrrole derivatives generally in good yields. The reaction was proposed to proceed via a tandem nucleophilic addition of carbene to the C=N bond of ketenimine followed by a stepwise [3+2] cycloaddition of the 1,3-dipolar intermediate with the C=C bond of ketenimine. This reaction provides a powerful protocol for the construction of novel polyfunctional thiazole-spiro-pyrrole or benzothiazole-spiro-pyrrole compounds that are not readily accessible by other methods.

  14. Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

    PubMed

    Pirali, Tracey; Faccio, Valeria; Mossetti, Riccardo; Grolla, Ambra A; Di Micco, Simone; Bifulco, Giuseppe; Genazzani, Armando A; Tron, Gian Cesare

    2010-02-01

    Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

  15. Improved Synthesis of 5-Substituted 1H-Tetrazoles via the [3+2] Cycloaddition of Nitriles and Sodium Azide Catalyzed by Silica Sulfuric Acid

    PubMed Central

    Du, Zhenting; Si, Changmei; Li, Youqiang; Wang, Yin; Lu, Jing

    2012-01-01

    A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%–95% yield. PMID:22606004

  16. Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers.

    PubMed

    Park, Sangjune; Kim, Hyunseok; Son, Jeong-Yu; Um, Kyusik; Lee, Sooho; Baek, Yonghyeon; Seo, Boram; Lee, Phil Ho

    2017-10-06

    The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

  17. The concern of emergence of multi-station reaction pathways that might make stepwise the mechanism of the 1,3-dipolar cycloadditions of azides and alkynes

    NASA Astrophysics Data System (ADS)

    Mohtat, Bita; Siadati, Seyyed Amir; Khalilzadeh, Mohammad Ali; Zareyee, Daryoush

    2018-03-01

    After hot debates on the concerted or stepwise nature of the mechanism of the catalyst-free 1,3-dipolar cycloadditions (DC)s, nowadays, it is being believed that for the reaction of each dipole and dipolarophile, there is a possibility that the reaction mechanism becomes stepwise, intermediates emerge, and the reaction becomes non-stereospecific. Yield of even minimal amounts of unwanted side products or stereoisomers as impurities could bring many troubles like difficult purification steps. In this project, we have made attempts to study all probable reaction channels of the azide cycloadditions with two functionalized alkynes, in order to answer this question: "is there any possibility that intermediates evolve in the catalyst-free click 1,3-DC reaction of azide-alkynes?". During the calculations, several multi-station reaction pathways supporting the stepwise and concerted mechanisms were detected. Also, the born-oppenheimer molecular dynamic (BOMD) simulation was used to find trustable geometries which could be emerged during the reaction coordinate.

  18. Solvent effect on copper-catalyzed azide-alkyne cycloaddition (CuAAC): synthesis of novel triazolyl substituted quinolines as potential anticancer agents.

    PubMed

    Ellanki, Amarender Reddy; Islam, Aminul; Rama, Veera Swamy; Pulipati, Ranga Prasad; Rambabu, D; Krishna, G Rama; Reddy, C Malla; Mukkanti, K; Vanaja, G R; Kalle, Arunasree M; Kumar, K Shiva; Pal, Manojit

    2012-05-15

    A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties when tested in vitro especially against breast cancer cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides†

    PubMed Central

    Hein, Jason E.

    2011-01-01

    Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(i) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science. PMID:20309487

  20. Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar Cycloaddition for Construction of Functional Pyrrolizidine Derivatives.

    PubMed

    Mao, Zhuo-Ya; Liu, Yi-Wen; Han, Pan; Dong, Han-Qing; Si, Chang-Mei; Wei, Bang-Guo; Lin, Guo-Qiang

    2018-02-16

    An efficient and step-economical approach to access functionalized pyrrolizidine derivatives by a one-pot tandem sequence, including an aldol condensation and subsequent 1,3-dipolar cycloaddition process, has been developed, starting from acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were amenable to this transformation, and the desired products, racemic 7a-7w and chiral 9a-9m, were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, in situ NMR studies revealed MgSO 4 could effectively promote the aldol condensation pathway in this tandem process.

  1. Advances in heterocycle synthesis via [3+m]-cycloaddition reactions involving an azaoxyallyl cation as the key intermediate.

    PubMed

    Xuan, Jun; Cao, Xia; Cheng, Xiao

    2018-05-17

    Heterocyclic compounds are widely found in many natural isolates and medicinally relevant compounds, as well as some fine chemicals. The development of general and efficient methods for the construction of heterocyclic compounds is one of the most important tasks in synthetic organic chemistry. Along these lines, [3+m]-cycloaddition reactions involving in situ generated azaoxyallyl cations as the 3-atom units have emerged as a powerful method for the synthesis of nitrogen-containing heterocycles. In this feature article, we highlight recent advances in this rapidly growing area, mainly focusing on the reaction design as well as the reaction mechanism.

  2. Electrochemically Protected Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

    PubMed Central

    Hong, Vu; Udit, Andrew K.; Evans, Richard A.; Finn, M.G.

    2012-01-01

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications requiring high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. The simple procedure efficiently achieves excellent yields of CuAAC products involving both small molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E1/2 = 60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E1/2 = -60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E1/2 ~ -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential established using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically-protected bioconjugations in air were performed using bacteriophage Qβ derivatized with azide moieties at surface lysine residues. The complete addressing of more than 600 reactive sites per particle was demonstrated within 12 hours of electrolysis with sub-stoichiometric quantities of Cu•3. PMID:18504727

  3. Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition.

    PubMed

    Hong, Vu; Udit, Andrew K; Evans, Richard A; Finn, M G

    2008-06-16

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications that require high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. This simple procedure efficiently achieves excellent yields of CuAAC products from both small-molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is also described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E(1/2)=60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E(1/2)=-60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E(1/2) approximately -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential that was established by using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically protected bioconjugations in air were performed by using bacteriophage Qbeta that was derivatized with azide moieties at surface lysine residues. Complete derivatization of more than 600 reactive sites per particle was demonstrated within 12 h of electrolysis with substoichiometric quantities of Cu3.

  4. Felkin-Anh stereoselectivity in cycloadditions of acetylketene: evidence for a concerted, pseudopericyclic pathway

    PubMed

    Shumway; Ham; Moer; Whittlesey; Birney

    2000-11-17

    The cycloadditions of acetylketene with alpha-chiral aldehydes and ketones are shown to be diastereoselective, forming a tertiary or quaternary chiral center at an acetal or ketal carbon with good stereocontrol. X-ray crystallography of a minor product (5b) shows that the major products (e.g., 4b) are those predicted by the Felkin-Anh model. Transition states are reported at the MP2/6-31G level for the addition of ethanal to formylketene and at the B3LYP/6-31G level for the addition of 2-phenylpropanal. The ground-state conformations of the reactants and products are used to rationalize the relative energies and geometries of the transition states without the need to invoke the Cieplak hypothesis. However, chiral substituents on the alpha-oxoketene show no diastereoselectivity. These experimental and computational results are only consistent with the nearly planar, pseudopericyclic transition state previously proposed.

  5. Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition.

    PubMed

    Szíjjártó, Csongor; Pershagen, Elias; Borbas, K Eszter

    2012-07-07

    Cu(I)-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates. The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual Eu(III) and Tb(III)-emission upon antenna-centred excitation.

  6. Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions

    NASA Astrophysics Data System (ADS)

    Newton, Christopher G.; Drew, Samuel L.; Lawrence, Andrew L.; Willis, Anthony C.; Paddon-Row, Michael N.; Sherburn, Michael S.

    2015-01-01

    The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.

  7. Rhodium-Catalyzed Denitrogenative [3+2] Cycloaddition: Access to Functionalized Hydroindolones and the Framework of Montanine-Type Amaryllidaceae Alkaloids.

    PubMed

    Yang, Hongjian; Hou, Shengtai; Tao, Cheng; Liu, Zhao; Wang, Chao; Cheng, Bin; Li, Yun; Zhai, Hongbin

    2017-09-18

    Rhodium-catalyzed denitrogenative [3+2] cycloaddition of 1-sulfonyl-1,2,3-triazoles with cyclic silyl dienol ethers has been developed for the synthesis of functionalized hydroindolones or their corresponding silyl ethers. The present method has been employed to construct synthetically valuable bicyclo[3.3.1]alkenone derivatives and pyrrolidine-ring-containing bicyclic indole compounds. As a further synthetic application, a stereoselective synthesis of 5,11-methanomorphanthridin-3-one, which shares a key skeleton with montanine-type Amaryllidaceae alkaloids has been achieved by using this chemistry. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    DOE PAGES

    Powers, Andrew R.; Ghiviriga, Ion; Abboud, Khalil A.; ...

    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)-N 3 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 ismore » a prerequisite for the reaction. The mechanistic conclusions mirror those proposed for the CuAAC reaction.« less

  9. Highly efficient and recyclable basic mesoporous zeolite catalyzed condensation, hydroxylation, and cycloaddition reactions.

    PubMed

    Sarmah, Bhaskar; Satpati, Biswarup; Srivastava, Rajendra

    2017-05-01

    Crystalline mesoporous ZSM-5 zeolite was prepared in the presence of 1,4-diazabicyclo[2.2.2]octane derived multi-cationic structure directing agent. The calcined form of the mesoprous zeolite was treated with NH 4 OH to obtain basic mesoporous ZSM-5. Catalyst was characterized by the complementary combination of X-ray diffraction, N 2 -adsorption, electron microscopes, and temperature programme desorption techniques. Catalytic activity of the basic mesoporous ZSM-5 was systematically assessed using Knoevenagel condensation reaction for the synthesis a wide range of substituted styrene. Applications of the catalyst were investigated in the benzamide hydroxylation for the synthesis of carbinolamides and one-pot, multi-component condensation reaction for the synthesis of naphthopyrans. Finally, the catalyst was evaluated in the cycloaddition of CO 2 to epoxide for the synthesis of cyclic carbonates. Recycling study shows that no significant decrease in the catalytic activity was observed after five recycles. Copyright © 2017. Published by Elsevier Inc.

  10. Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I)-catalyzed cycloaddition.

    PubMed

    Tirino, Pasquale; Laurino, Rosaria; Maglio, Giovanni; Malinconico, Mario; d'Ayala, Giovanna Gomez; Laurienzo, Paola

    2014-11-04

    In this work, a well-defined hydrogel was developed by coupling chitosan with PEO through "click chemistry". Azide functionalities were introduced onto chitosan, through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent of coupling is strictly dependent on the amount of azido groups on chitosan, which in turn can be easily modulated. The obtained hydrogel, with a crosslinking degree of around 90%, showed interesting swelling properties. With respect to chitosan hydrogels reported in literature, a considerably higher equilibrium uptake was reached (940%). The possibility to control the crosslinking degree of hydrogel and its capability to rapidly absorb high amounts of water make this material suitable for several applications, such as controlled drug release and wound healing. Copyright © 2014. Published by Elsevier Ltd.

  11. Dual function catalysts. Dehydrogenation and asymmetric intramolecular Diels-Alder cycloaddition of N-hydroxy formate esters and hydroxamic acids: evidence for a ruthenium-acylnitroso intermediate.

    PubMed

    Chow, Chun P; Shea, Kenneth J

    2005-03-23

    The chiral ruthenium salen complex, 13b, functions as an efficient catalyst for the sequential oxidation and asymmetric Diels-Alder cycloaddition of hydroxamic acids and N-hydroxy formate esters. This result provides evidence for the formation of a ruthenium-nitroso formate (acyl nitroso) intermediate. The Diels-Alder precursors are prepared from simple building blocks, and the cycloadducts, bridged oxazinolactams, can serve as useful intermediates in organic synthesis.

  12. Excess Substrate is a Spectator Ligand in a Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of Alkenyl Isocyanates with Tolanes

    PubMed Central

    Oinen, Mark Emil; Yu, Robert T.; Rovis, Tomislav

    2009-01-01

    Excess substrate has been identified as an unintended spectator ligand affecting enantioselectivity in the [2+2+2] cycloaddition of alkenyl isocyanates with tolanes. Replacement of excess substrate with an exogenous additive affords products with consistent and higher ee’s. The increase in enantioselectivity is the result of a change in composition of a proposed rhodium(III) intermediate on the catalytic cycle. The net result is a rational probe of a short-lived rhodium(III) intermediate, and gives insight that may have applications in many rhodium catalyzed reactions. PMID:19803471

  13. Rh-Catalyzed [3 + 2] Cycloaddition of 1-Sulfonyl-1,2,3-triazoles: Access to the Framework of Aspidosperma and Kopsia Indole Alkaloids.

    PubMed

    Li, Yun; Zhang, Qingyu; Du, Qiucheng; Zhai, Hongbin

    2016-08-19

    A Rh(II)-catalyzed dearomative intramolecular [3 + 2] dipolar cycloaddition involving the indolic C2-C3 carbon-carbon double bond has been developed. The reaction was launched from the triazole moiety within the substrate and proceeded efficiently under mild conditions. A wide range of functional groups could be tolerated. These features render the current reaction a highly useful tool for the synthesis of polycyclic indole alkaloids, as showcased by a rapid assembly of the core structure of Aspidosperma and the related alkaloids.

  14. Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition

    PubMed Central

    Sato, Michio; Yagishita, Fumitoshi; Mino, Takashi; Uchiyama, Nahoko; Patel, Ashay; Chooi, Yit-Heng; Goda, Yukihiro; Xu, Wei; Noguchi, Hiroshi; Yamamoto, Tsuyoshi; Hotta, Kinya; Houk, Kendall N.; Tang, Yi

    2016-01-01

    Understanding enzymatic Diels—Alder (DA) reactions that can form complex natural product scaffold is of considerable interest. Sch 210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form via a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo 1 and a diastereomeric exo adducts of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1. PMID:26360642

  15. Improved metal-adhesive polymers from copper(I)-catalyzed azide-alkyne cycloaddition.

    PubMed

    Accurso, Adrian A; Delaney, Mac; O'Brien, Jeff; Kim, Hyonny; Iovine, Peter M; Díaz Díaz, David; Finn, M G

    2014-08-18

    Electrically conductive adhesive polymers offer many potential advantages relative to Sn-Pb solders, including reduced toxicity, low cost, low processing temperatures, and the ability to make application-specific formulations. Polymers generated from the copper(I)-catalyzed cycloaddition (CuAAC) reaction between multivalent azides and alkynes have previously been identified as strong metal-binding adhesives. Herein we demonstrate that the performance of these materials can be remarkably improved by the incorporation of a flexibility-inducing difunctionalized component and a tertiary amine additive in optimized concentrations. The best formulations were identified by means of rapid adhesion testing of a library of potential candidates by using a custom-built instrument and validated in an American Society for Testing and Materials (ASTM)-standard lap-shear test. Characteristic phase transitions were identified by differential scanning calorimetry (DSC) for adhesives with and without the additives as a function of curing temperature. The incorporation of flexible components was found to more than double the strength of the adhesive. Moreover, the adhesive was made electrically conductive by the inclusion of 20 wt% silver-coated copper flakes and further improved in this regard by the incorporation of multiwalled carbon nanotubes in the formulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Viability of a [2 + 2 + 1] Hetero-Pauson-Khand Cycloaddition Strategy toward Securinega Alkaloids: Synthesis of the BCD-Ring Core of Securinine and Related Alkaloids.

    PubMed

    Chirkin, Egor; Michel, Sylvie; Porée, François-Hugues

    2015-07-02

    Preliminary results related to the development of [2 + 2 + 1]-oxa-hetero-Pauson-Khand cycloaddition strategy toward the Securinega alkaloids are reported. The critical tricyclic BCD-ring core was assembled in only nine linear steps from cheap 4-hydroxy-l-proline. The study provides valuable insight into the scope of a rare hetero-Pauson-Khand reaction, a powerful tool for the rapid construction of butenolide-containing natural products.

  17. λ5-Phosphorus-Containing α-Diazo Compounds: A Valuable Tool for Accessing Phosphorus-Functionalized Molecules.

    PubMed

    Marinozzi, Maura; Pertusati, Fabrizio; Serpi, Michaela

    2016-11-23

    The compounds characterized by the presence of a λ 5 -phosphorus functionality at the α-position with respect to the diazo moiety, here referred to as λ 5 -phosphorus-containing α-diazo compounds (PCDCs), represent a vast class of extremely versatile reagents in organic chemistry and are particularly useful in the preparation of phosphonate- and phosphinoxide-functionalized molecules. Indeed, thanks to the high reactivity of the diazo moiety, PCDCs can be induced to undergo a wide variety of chemical transformations. Among them are carbon-hydrogen, as well as heteroatom-hydrogen insertion reactions, cyclopropanation, ylide formation, Wolff rearrangement, and cycloaddition reactions. PCDCs can be easily prepared from readily accessible precursors by a variety of different methods, such as diazotization, Bamford-Stevens-type elimination, and diazo transfer reactions. This evidence along with their relative stability and manageability make them appealing tools in organic synthesis. This Review aims to demonstrate the ongoing utility of PCDCs in the modern preparation of different classes of phosphorus-containing compounds, phosphonates, in particular. Furthermore, to address the lack of precedent collective papers, this Review also summarizes the methods for PCDCs preparation.

  18. 7-Chloroquinolinotriazoles: synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies.

    PubMed

    Pereira, Guilherme R; Brandão, Geraldo Célio; Arantes, Lucas M; de Oliveira, Háliton A; de Paula, Renata Cristina; do Nascimento, Maria Fernanda A; dos Santos, Fábio M; da Rocha, Ramon K; Lopes, Júlio César D; de Oliveira, Alaíde Braga

    2014-02-12

    Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between 4-azido-7-chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 μM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 μM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloaddition between azides and alkynes.

    PubMed

    Tron, Gian Cesare; Pirali, Tracey; Billington, Richard A; Canonico, Pier Luigi; Sorba, Giovanni; Genazzani, Armando A

    2008-03-01

    In recent years, there has been an ever-increasing need for rapid reactions that meet the three main criteria of an ideal synthesis: efficiency, versatility, and selectivity. Such reactions would allow medicinal chemistry to keep pace with the multitude of information derived from modern biological screening techniques. The present review describes one of these reactions, the 1,3-dipolar cycloaddition ("click-reaction") between azides and alkynes catalyzed by copper (I) salts. The simplicity of this reaction and the ease of purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The present review will outline the accomplishments of this strategy achieved so far and outline some of medicinal chemistry applications in which click-chemistry might be relevant in the future. (c) 2007 Wiley Periodicals, Inc.

  20. 5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine–Alkene 1,3-Dipolar Cycloaddition

    PubMed Central

    Pla, Daniel; Tan, Derek S.; Gin, David Y.

    2014-01-01

    A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (±)-newbouldine and withasomnine. PMID:25114776

  1. Natrolite zeolite supported copper nanoparticles as an efficient heterogeneous catalyst for the 1,3-diploar cycloaddition and cyanation of aryl iodides under ligand-free conditions.

    PubMed

    Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad; Rostami-Vartooni, Akbar; Khalaj, Mehdi

    2015-09-01

    In this paper, we report the preparation of Natrolite zeolite supported copper nanoparticles as a heterogeneous catalyst for 1,3-diploar cycloaddition and synthesis aryl nitriles from aryl iodides under ligand-free conditions. The catalyst was characterized using XRD, SEM, TEM, EDS and TG-DTA. The experimental procedure is simple, the products are formed in high yields and the catalyst can be recycled and reused several times without any significant loss of catalytic activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [4 + 3] Cycloaddition of aromatic α,β-unsaturated aldehydes and ketones with epoxides: one-step approach to synthesize seven-membered oxacycles catalyzed by Lewis acid.

    PubMed

    Zhou, Yu-Qiang; Wang, Nai-Xing; Zhou, Shu-Bao; Huang, Zhong; Cao, Linghua

    2011-01-21

    A novel intermolecular [4 + 3] cycloaddition method to construct 1,4-dioxide seven-membered oxacycles was developed. This one-step method was carried out in the presence of catalytic amount of (C(2)H(5))(2)OBF(3) under mild conditions. Seven-membered oxacycles and some natural compounds could be easily synthesized via this protocol. Control experiments were carried out and possible mechanism for the reaction was proposed. Asymmetric reactions were proceeded and 3e was obtained with moderate ee value.

  3. Electron density reactivity indexes of the tautomeric/ionization forms of thiamin diphosphate.

    PubMed

    Jaña, Gonzalo A; Delgado, Eduardo J

    2013-09-01

    The generation of the highly reactive ylide in thiamin diphosphate catalysis is analyzed in terms of the nucleophilicity of key atoms, by means of density functional calculations at X3LYP/6-31++G(d,p) level of theory. The Fukui functions of all tautomeric/ionization forms are calculated in order to assess their reactivity. The results allow to conclude that the highly conserved glutamic residue does not protonate the N1' atom of the pyrimidyl ring, but it participates in a strong hydrogen bonding, stabilizing the eventual negative charge on the nitrogen, in all forms involved in the ylide generation. This condition provides the necessary reactivity on key atoms, N4' and C2, to carry out the formation of the ylide required to initiate the catalytic cycle of ThDP-dependent enzymes. This study represents a new approach for the ylide formation in ThDP catalysis.

  4. Ni(ClO4)(2)-catalysed regio- and diastereoselective [3+2] cycloaddition of indoles and aryl oxiranyl-dicarboxylates/diketones: a facile access to furo[3,4-b]indoles.

    PubMed

    Zhang, Jieming; Chen, Zuliang; Wu, Hai-Hong; Zhang, Junliang

    2012-02-07

    Ni(ClO(4))(2)·6H(2)O-catalysed regioselective and diastereoselective [3+2]-annulations of aryl oxiranyl-dicarboxylates and indoles via selective C-C bond cleavage of oxirane were revealed. The cycloadditions proceed smoothly with high regio- and diastereoselectivity under mild conditions leading to 1H-furo[3,4-b]indoles in good to excellent yields. This journal is © The Royal Society of Chemistry 2012

  5. Exploring the Stereochemistry of the Wittig Reaction: The Unexpected Influence of a Nominal Spectator Ion

    ERIC Educational Resources Information Center

    Hanson, John; Dasher, Bill; Scharrer, Eric; Hoyt, Tim

    2010-01-01

    Students in the second-semester organic chemistry laboratory perform a Wittig reaction between butylidenetriphenylphosphorane (an ylide) and benzaldehyde and determine the relative percentages of the cis and trans isomers of the 1-phenyl-1-pentene product. Because of the highly reactive nature of this unstabilized ylide, students are introduced to…

  6. Antifungal activity of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides: A novel type of compound afforded by azide-enolate (3+2) cycloaddition.

    PubMed

    González-Calderón, Davir; Mejía-Dionicio, María G; Morales-Reza, Marco A; Aguirre-de Paz, José G; Ramírez-Villalva, Alejandra; Morales-Rodríguez, Macario; Fuentes-Benítes, Aydeé; González-Romero, Carlos

    2016-12-01

    The first report of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides (7a and 7b) is described herein. Azide-enolate (3+2) cycloaddition afforded the synthesis of this novel type of compound. Antifungal activity was evaluated in vitro against four filamentous fungi (Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis) as well as nine species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 7a and 7b are promising candidates for complementary biological studies due to their good activity against Candida spp. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The [2+2] Cycloaddition-Retroelectrocyclization (CA-RE) Click Reaction: Facile Access to Molecular and Polymeric Push-Pull Chromophores.

    PubMed

    Michinobu, Tsuyoshi; Diederich, François

    2018-03-26

    The [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction between electron-rich alkynes and electron-deficient alkenes is an efficient procedure to create nonplanar donor-acceptor (D-A) chromophores in both molecular and polymeric platforms. They feature attractive properties including intramolecular charge-transfer (ICT) bands, nonlinear optical properties, and redox activities for use in next-generation electronic and optoelectronic devices. This Review summarizes the development of the CA-RE reaction, starting from the initial reports with organometallic compounds to the extension to purely organic systems. The structural requirements for rapid, high-yielding transformations with true click chemistry character are illustrated by examples that include the broad alkyne and alkene substitution modes. The CA-RE click reaction has been successfully applied to polymer synthesis, with the resulting polymeric push-pull chromophores finding many interesting applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Rh(I)-catalyzed intramolecular [2 + 2 + 1] cycloaddition of allenenes: Construction of bicyclo[4.3.0]nonenones with an angular methyl group and tricyclo[6.4.0.01,5]dodecenone

    PubMed Central

    Inagaki, Fuyuhiko; Itoh, Naoya; Hayashi, Yujiro; Matsui, Yumi

    2011-01-01

    Summary The [RhCl(CO)dppp]2-catalyzed intramolecular carbonylative [2 + 2 + 1] cycloaddition of allenenes was developed to prepare bicyclo[4.3.0]nonenones possessing a methyl group at the ring junction, which is difficult to achieve by the Pauson–Khand reaction of the corresponding enynes. This method also provided a new procedure for the construction of the tricyclo[6.4.0.01,5]dodecenone framework in a satisfactory yield. PMID:21512593

  9. Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of α-Diazo Pyrazoleamides.

    PubMed

    Lin, Xiaobin; Tang, Yu; Yang, Wei; Tan, Fei; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

    2018-03-07

    Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium ylides (Doyle-Kirmse reaction) has proven surprisingly elusive using classic chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in fine discrimination of the heterotopic lone pairs of sulfur and chirality inversion at sulfur of sulfonium ylides. Here, we show that the synergistic merger of new α-diazo pyrazoleamides and a chiral N, N'-dioxide-nickel(II) complex catalyst enables a highly enantioselective Doyle-Kirmse reaction. The pyrazoleamide substituent serves as both an activating and a directing group for the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate in the assistance of a dual-tasking nickel(II) complex. An alternative chiral Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even for the reaction of a symmetric diallylsulfane. The majority of transformations over a series of aryl- or vinyl-substituted α-diazo pyrazoleamindes and sulfides proceed rapidly (within 5-20 min in most cases) with excellent results (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle-Kirmse reaction.

  10. Branched Polyhedral Oligomeric Silsesquioxane Nanoparticles Prepared via Strain-Promoted 1,3-Dipolar Cycloadditions

    PubMed Central

    Ledin, Petr A.; Xu, Weinan; Friscourt, Frédéric; Boons, Geert-Jan; Tsukruk, Vladimir V.

    2016-01-01

    Conjugation of small organic molecules and polymers to polyhedral oligosilsesquioxane (POSS) cores results in novel hybrid materials with unique physical characteristics. We report here an approach in which star-shaped organic–inorganic scaffolds bearing eight cyclooctyne moieties can be rapidly functionalized via strain-promoted azide–alkyne cycloaddition (SPAAC) to synthesize a series of nearly monodisperse branched core–shell nanoparticles with hydrophobic POSS cores and hydrophilic arms. We established that SPAAC is a robust method for POSS core octafunctionalization with the reaction rate constant of 1.9 × 10−2 M−1 s−1. Functionalization with poly(ethylene glycol) (PEG) azide, fluorescein azide, and unprotected lactose azide gave conjugates which represent different classes of compounds: polymer conjugates, fluorescent dots, and bioconjugates. These resulting hybrid compounds were preliminarily tested for their ability to self-assemble in solution and at the air–water interface. We observed the formation of robust smooth Langmuir monolayers with diverse morphologies. We found that polar lactose moieties are completely submerged into the subphase whereas the relatively hydrophobic fluorescein arms had extended conformation at the interface, and PEG arms were partially submerged. Finally, we observed the formation of stable micelles with sizes between 70 and 160 nm in aqueous solutions with size and morphology of the structures dependent on the molecular weight and the type of the peripheral hydrophilic moieties. PMID:26131712

  11. TiO2 Photocatalysis in Aromatic "Redox Tag"-Guided Intermolecular Formal [2 + 2] Cycloadditions.

    PubMed

    Okada, Yohei; Maeta, Naoya; Nakayama, Kaii; Kamiya, Hidehiro

    2018-05-04

    Since the pioneering work by Macmillan, Yoon, and Stephenson, homogeneous photoredox catalysis has occupied a central place in new reaction development in the field of organic chemistry. While heterogeneous semiconductor photocatalysis has also been studied extensively, it has generally been recognized as a redox option in inorganic chemistry where such "photocatalysis" is most often used to catalyze carbon-carbon bond cleavage and not in organic chemistry where bond formation is usually the focal point. Herein, we demonstrate that titanium dioxide photocatalysis is a powerful redox option to construct carbon-carbon bonds by using intermolecular formal [2 + 2] cycloadditions as models. Synergy between excited electrons and holes generated upon irradiation is expected to promote the overall net redox neutral process. Key for the successful application is the use of a lithium perchlorate/nitromethane electrolyte solution, which exhibits remarkable Lewis acidity to facilitate the reactions of carbon-centered radical cations with carbon nucleophiles. The reaction mechanism is reasonably understood based on both intermolecular and intramolecular single electron transfer regulated by an aromatic "redox tag". Most of the reactions were completed in less than 30 min even in aqueous and/or aerobic conditions without the need for sacrificial reducing or oxidizing substrates generally required for homogeneous photoredox catalysis.

  12. Cyclic Multiblock Copolymers via Combination of Iterative Cu(0)-Mediated Radical Polymerization and Cu(I)-Catalyzed Azide-Alkyne Cycloaddition Reaction.

    PubMed

    Xiao, Lifen; Zhu, Wen; Chen, Jiqiang; Zhang, Ke

    2017-02-01

    Cyclic multiblock polymers with high-order blocks are synthesized via the combination of single-electron transfer living radical polymerization (SET-LRP) and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The linear α,ω-telechelic multiblock copolymer is prepared via SET-LRP by sequential addition of different monomers. The SET-LRP approach allows well control of the block length and sequence as A-B-C-D-E, etc. The CuAAC is then performed to intramolecularly couple the azide and alkyne end groups of the linear copolymer and produce the corresponding cyclic copolymer. The block sequence and the cyclic topology of the resultant cyclic copolymer are confirmed by the characterization of 1 H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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

  14. Efficient approach to androstene-fused arylpyrazolines as potent antiproliferative agents. Experimental and theoretical studies of substituent effects on BF(3)-catalyzed intramolecular [3 + 2] cycloadditions of olefinic phenylhydrazones.

    PubMed

    Frank, Eva; Mucsi, Zoltán; Zupkó, István; Réthy, Borbála; Falkay, George; Schneider, Gyula; Wölfling, János

    2009-03-25

    Highly diastereoselective Lewis acid induced intramolecular 1,3-dipolar cycloadditions of alkenyl phenylhydrazones (containing various substituents on the aromatic ring) obtained from a d-secopregnene aldehyde were carried out under fairly mild conditions to furnish androst-5-ene-fused arylpyrazolines in good to excellent yields. The ability of phenylhydrazones to undergo cyclization was found to be affected significantly by the electronic features of the substituents on the aromatic moiety. The rates of the ring-closure reactions were observed to be increased by electron-donating and decreased by electron-withdrawing groups. The experimental findings on the BF(3)-catalyzed transformations were supported by calculations of the proposed mechanism at the BLYP/6-31G(d) level of theory, indicating a noteworthy dependence, mainly of the initial complexation step, and hence of the whole process, on the character of the substituent. The cycloaddition was estimated to occur via a zwitterionic intermediate rather than involving a pure concerted mechanism. The antiproliferative activities of the structurally related pyrazoline derivatives were tested in vitro on three malignant human cell lines (HeLa, MCF7, and A431): the microculture tetrazolium assay revealed that several compounds exerted marked cell growth-inhibitory effects. The highest cytotoxic activities, displayed by the p-methoxyphenylpyrazoline derivative 7d (IC(50) values: 2.01, 2.16, and 1.41 microM on HeLa, MCF7, and A341 cells, respectively), were better than those of cisplatin (IC(50) values: 12.43, 9.63, and 2.84 microM, respectively).

  15. Enhancing the Scope of the Diels-Alder Reaction through Isonitrile Chemistry: Emergence of a New Class of Acyl-Activated Dienophiles

    PubMed Central

    Townsend, Steven D.; Wu, Xiangyang; Danishefsky, Samuel J.

    2012-01-01

    α,β-Unsaturated imides, formylated at the nitrogen atom, comprise a new and valuable family of dienophiles for servicing Diels-Alder reactions. These systems are assembled through extension of recently discovered isonitrile chemistry to the domain of α,β-unsaturated acids. Cycloadditions are facilitated by Et2AlCl, presumably via chelation between the two carbonyl groups of the N-formyl amide. Applications of the isonitrile/Diels-Alder logic to the IMDA reaction, as well as methodologies to modify the N-formyl amide of the resultant cycloaddition product, are described. It is expected that this easily executed chemistry will provide a significant enhancement for application of Diels-Alder reactions to many synthetic targets. PMID:22708980

  16. N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

    PubMed

    Montiel-Herrera, Marcelino; Gandini, Alessandro; Goycoolea, Francisco M; Jacobsen, Neil E; Lizardi-Mendoza, Jaime; Recillas-Mota, Maricarmen; Argüelles-Monal, Waldo M

    2015-09-05

    In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Catalytic "active-metal" template synthesis of [2]rotaxanes, [3]rotaxanes, and molecular shuttles, and some observations on the mechanism of the cu(i)-catalyzed azide-alkyne 1,3-cycloaddition.

    PubMed

    Aucagne, Vincent; Berna, José; Crowley, James D; Goldup, Stephen M; Hänni, Kevin D; Leigh, David A; Lusby, Paul J; Ronaldson, Vicki E; Slawin, Alexandra M Z; Viterisi, Aurélien; Walker, D Barney

    2007-10-03

    A synthetic approach to rotaxane architectures is described in which metal atoms catalyze covalent bond formation while simultaneously acting as the template for the assembly of the mechanically interlocked structure. This "active-metal" template strategy is exemplified using the Huisgen-Meldal-Fokin Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes (the CuAAC "click" reaction). Coordination of Cu(I) to an endotopic pyridine-containing macrocycle allows the alkyne and azide to bind to metal atoms in such a way that the metal-mediated bond-forming reaction takes place through the cavity of the macrocycle--or macrocycles--forming a rotaxane. A variety of mono- and bidentate macrocyclic ligands are demonstrated to form [2]rotaxanes in this way, and by adding pyridine, the metal can turn over during the reaction, giving a catalytic active-metal template assembly process. Both the stoichiometric and catalytic versions of the reaction were also used to synthesize more complex two-station molecular shuttles. The dynamics of the translocation of the macrocycle by ligand exchange in these two-station shuttles could be controlled by coordination to different metal ions (rapid shuttling is observed with Cu(I), slow shuttling with Pd(II)). Under active-metal template reaction conditions that feature a high macrocycle:copper ratio, [3]rotaxanes (two macrocycles on a thread containing a single triazole ring) are also produced during the reaction. The latter observation shows that under these conditions the mechanism of the Cu(I)-catalyzed terminal alkyne-azide cycloaddition involves a reactive intermediate that features at least two metal ions.

  18. The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.

    PubMed

    Donckele, Etienne J; Finke, Aaron D; Ruhlmann, Laurent; Boudon, Corinne; Trapp, Nils; Diederich, François

    2015-07-17

    The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

  19. Unprecedented intramolecular [3 + 2] cycloadditions of azido-ketenimines and azido-carbodiimides. Synthesis of indolo[1,2-a]quinazolines and tetrazolo[5,1-b]quinazolines.

    PubMed

    Alajarin, Mateo; Bonillo, Baltasar; Ortin, Maria-Mar; Orenes, Raul-Angel; Vidal, Angel

    2011-10-07

    N-(2-azidomethyl)phenyl ketenimines and N-(2-azidomethyl)phenyl-N'-alkyl(aryl) carbodiimides undergo, under mild thermal conditions, intramolecular [3 + 2] cycloaddition reactions between the azido group and either the C=C or the distal C=N double bonds of the ketenimine and carbodiimide functions respectively. The reaction products are indolo[1,2-a]quinazolines and/or indolo[2,1-b]quinazolines in the case of azido-ketenimines, and tetrazolo[5,1-b]quinazolines in the case of azido-carbodiimides. The formation of the two classes of indoloquinazolines implies the ulterior dinitrogen extrusion from the non-isolated, putative [3 + 2] cycloadducts between the azide and ketenimine functions, whereas in the case of azido-carbodiimides the initial cycloadducts, tetrazoloquinazolines, were cleanly isolated and further converted into 2-aminoquinazolines by thermally induced dinitrogen extrusion.

  20. On the regioselectivity of the Diels–Alder cycloaddition to C60 in high spin states† †Electronic supplementary information (ESI) available: Cartesian coordinates and energies of all species involved, the aromaticity results (HOMA, MCI, and INB), Gibbs and electronic reaction energies and energy barriers for the reaction between 2S+1C60 (S = 0–6) and cyclopentadiene as well as for the reaction between 2S+1C60 (S = 0, 1) and isoindene/indene, and the experimental results with different reagent concentrations, type of irradiation, and conditions for the cycloaddition of indene and C60. See DOI: 10.1039/c7cp07965f

    PubMed Central

    El Bakouri, Ouissam; Garcia-Borràs, Marc; Girón, Rosa M.; Filippone, Salvatore

    2018-01-01

    Controlling the regioselectivity in the exohedral functionalization of fullerenes and endohedral metallofullerenes is essential to produce specific desired fullerene derivatives. In this work, using density functional theory (DFT) calculations, we show that the regioselectivity of the Diels–Alder (DA) cycloaddition of cyclopentadiene to 2S+1C60 changes from the usual [6,6] addition in the singlet ground state to the [5,6] attack in high spin states of C60. Changes in the aromaticity of the five- and six-membered rings when going from singlet to high spin C60 provide a rationale to understand this regioselectivity change. Experimentally, however, we find that the DA cycloaddition of isoindene to triplet C60 yields the usual [6,6] adduct. Further DFT calculations and computational analysis give an explanation to this unanticipated experimental result by showing the presence of an intersystem crossing close to the formed triplet biradical intermediate. PMID:29417103

  1. Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition: Experimental and Theoretical Studies.

    PubMed

    Escorihuela, Jorge; Das, Anita; Looijen, Wilhelmus J E; van Delft, Floris L; Aquino, Adelia J A; Lischka, Hans; Zuilhof, Han

    2018-01-05

    Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne-1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH ⧧ ) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH ⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3-8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.

  2. Kinetics of the Strain-Promoted Oxidation-Controlled Cycloalkyne-1,2-quinone Cycloaddition: Experimental and Theoretical Studies

    PubMed Central

    2017-01-01

    Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne–1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH⧧) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3–8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches. PMID:29260879

  3. Synthesis of 1,3-bis(tetracyano-2-azulenyl-3-butadienyl)azulenes by the [2+2] cycloaddition-retroelectrocyclization of 1,3-bis(azulenylethynyl)azulenes with tetracyanoethylene.

    PubMed

    Shoji, Taku; Maruyama, Mitsuhisa; Maruyama, Akifumi; Ito, Shunji; Okujima, Tetsuo; Toyota, Kozo

    2014-09-08

    1,3-Bis(azulenylethynyl)azulene derivatives 9-14 have been prepared by palladium-catalyzed alkynylation of 1-ethynylazulene 8 with 1,3-diiodoazulene 1 or 1,3-diethynylazulene 2 with the corresponding haloazulenes 3-7 under Sonogashira-Hagihara conditions. Bis(alkynes) 9-14 reacted with tetracyanoethylene (TCNE) in a formal [2+2] cycloaddition-retroelectrocyclization reaction to afford the corresponding new bis(tetracyanobutadiene)s (bis(TCBDs)) 15-20 in excellent yields. The redox behavior of bis(TCBD)s 15-20 was examined by using CV and differential pulse voltammetry (DPV), which revealed their reversible multistage reduction properties under the electrochemical conditions. Moreover, a significant color change of alkynes 9-14 and TCBDs 15-20 was observed by visible spectroscopy under the electrochemical reduction conditions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mechanistic studies of 1,3-dipolar cycloadditions of bicyclic thioisomünchnones with alkenes. A computational rationale focused on donor-acceptor interactions.

    PubMed

    García de la Concepción, Juan; Ávalos, Martín; Cintas, Pedro; Jiménez, José L; Light, Mark E

    2018-05-09

    This paper describes a mechanistic study, with the interplay of experiment and theory, on the cycloadditions of a bicyclic mesoionic 1,3-dipole versus a series of representative symmetrical (1-phenyl-1H-pyrrole-2,5-dione and dimethyl maleate) and asymmetrical [(E)-(2-nitrovinyl)benzene, acrylonitrile, and but-3-en-2-one] olefinic dipolarophiles. These results allow a comparative analysis with monocyclic dipoles and open further avenues to structurally diversified heteroatom-rich rings. The unichiral version of the bicyclic dipole leads to adducts containing up to five chiral centers, whose formation proceeds with high levels of facial stereoinduction in reactions involving bulky dipolarophiles. The second and largest part of this study provides a theoretical interrogation on the pericyclic mechanism with DFT-methods [M06-2X/6-311++G(d,p)]. In order to get further mechanistic insights, we have also explored charge transfers between reaction partners using NBO analysis, which satisfactorily justifies the stereochemical outcome.

  5. Towards understanding the kinetic behaviour and limitations in photo-induced copper(i) catalyzed azide-alkyne cycloaddition (CuAAC) reactions.

    PubMed

    El-Zaatari, Bassil M; Shete, Abhishek U; Adzima, Brian J; Kloxin, Christopher J

    2016-09-14

    The kinetic behaviour of the photo-induced copper(i) catalyzed azide-alkyne cycloaddition (CuAAC) reaction was studied in detail using real-time Fourier transform infrared (FTIR) spectroscopy on both a solvent-based monofunctional and a neat polymer network forming system. The results in the solvent-based system showed near first-order kinetics on copper and photoinitiator concentrations up to a threshold value in which the kinetics switch to zeroth-order. This kinetic shift shows that the photo-CuAAC reaction is not susceptible from side reactions such as copper disproportionation, copper(i) reduction, and radical termination at the early stages of the reaction. The overall reaction rate and conversion is highly dependent on the initial concentrations of photoinitiator and copper(ii) as well as their relative ratios. The conversion was decreased when an excess of photoinitiator was utilized compared to its threshold value. Interestingly, the reaction showed an induction period at relatively low intensities. The induction period is decreased by increasing light intensity and photoinitiator concentration. The reaction trends and limitations were further observed in a solventless polymer network forming system, exhibiting a similar copper and photoinitiator threshold behaviour.

  6. Towards understanding the kinetic behaviour and limitations in photo-induced copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reactions

    PubMed Central

    El-Zaatari, Bassil M.; Shete, Abhishek U.; Adzima, Brian J.; Kloxin, Christopher J.

    2016-01-01

    The kinetic behaviour of the photo-induced copper(I) catalyzed azide—alkyne cycloaddition (CuAAC) reaction was studied in detail using real-time Fourier Transform Infrared Spectroscopy (FTIR) on both a solvent-based monofunctional and a neat polymer network forming system. The results in the solvent-based system showed near first-order kinetics on copper and photoinitiator concentrations up to a threshold value in which the kinetics switch to zeroth-order. This kinetic shift shows that the photo-CuAAC reaction is not suseptible from side reactions such as copper disproportionation, copper(I) reduction, and radical termination at the early stages of the reaction. The overall reaction rate and conversion is highly dependent on the initial concentrations of photoinitiator and copper(II), as well as their relative ratios. The conversion was decreased when an excess of photoinitiator was utilized compared to its threshold value. Interestingly, the reaction showed an induction period at relatively low intensities. The induction period is decreased by increasing light intensity, and photoinitiator concentration. The reaction trends and limitations were further observed in a solventless polymer network forming system, exhibiting a similar copper and photoinitiator threshold behaviour. PMID:27711587

  7. 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

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

    PubMed

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

    2016-01-21

    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 1 st 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.

  9. Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines.

    PubMed

    Soheili, Arash; Tambar, Uttam K

    2011-08-24

    We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.

  10. Metal-Free Poly-Cycloaddition of Activated Azide and Alkynes toward Multifunctional Polytriazoles: Aggregation-Induced Emission, Explosive Detection, Fluorescent Patterning, and Light Refraction.

    PubMed

    Wu, Yongwei; He, Benzhao; Quan, Changyun; Zheng, Chao; Deng, Haiqin; Hu, Rongrong; Zhao, Zujin; Huang, Fei; Qin, Anjun; Tang, Ben Zhong

    2017-09-01

    The metal-free click polymerization (MFCP) of activated alkynes and azides or activated azide and alkynes have been developed into powerful techniques for the construction of polytriazoles without the obsession of metallic catalyst residues problem. However, the MFCP of activated azides and alkynes is rarely applied in preparation of functional polytriazoles. In this paper, soluble multifunctional polytriazoles (PIa and PIb) with high weight-average molecular weights (M w up to 32 000) are prepared via the developed metal-free poly-cycloaddition of activated azide and alkynes in high yields (up to 90%). The resultant PIa and PIb are thermally stable, and show aggregation-induced emission characteristics, enabling their aggregates to detect explosives with superamplification effect. Moreover, thanks to their containing aromatic rings and polar moieties, PIa and PIb exhibit high refractive indices. In addition, they can also be cross-linked upon UV irradiation to generate 2D fluorescent patterning due to their remaining azide groups and containing ester groups. Thus, these multifunctional polytriazoles are potentially applicable in the optoelectronic and sensing fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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.

  12. 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

  13. On the mechanism of nitrosoarene-alkyne cycloaddition.

    PubMed

    Penoni, Andrea; Palmisano, Giovanni; Zhao, Yi-Lei; Houk, Kendall N; Volkman, Jerome; Nicholas, Kenneth M

    2009-01-21

    indole, was reproduced by the calculations of PhNO + PhC[triple bond]CH; the rate-limiting step for formation of the 2-substituted indole is higher in energy by 11.6 kcal/mol. The effects of -NO(2), -CN, -Cl, -Br, -Me, and -OMe substituents were computed for the reactions of p-X-C(6)H(4)NO with PhC[triple bond]CH and of PhNO and/or p-NO(2)-C(6)H(4)NO with p-Y-C(6)H(4)C[triple bond]CH. The activation energies for the set of p-X-C(6)H(4)NO vary by 4.3 kcal/mol and follow the trend found experimentally, with electron-withdrawing X groups accelerating the reactions. The range of barriers for the p-Y-C(6)H(4)C[triple bond]CH reactions is smaller, about 1.5 and 1.8 kcal/mol in the cases of PhNO and p-NO(2)-PhNO, respectively. In agreement with the experiments, electron-donating Y groups on the alkyne accelerate the reactions with p-NO(2)-C(6)H(4)NO, while both ED and EW groups are predicted to facilitate the reaction. The calculated kinetic isotope effect for the reaction of C(6)H(5)NO/C(6)D(5)NO with PhC[triple bond]CH is negligible (as found experimentally) while that for PhC[triple bond]CH/PhC[triple bond]CD with PhNO (0.7) differs somewhat from the experiment (1.1). Taken together the experimental and computational results point to the operation of a stepwise diradical cycloaddition, with rate-limiting N-C bond formation and rapid C-C connection to form a bicyclic cyclohexadienyl-N-oxyl diradical, followed by fast tautomerization to the N-hydroxyindole product.

  14. Double [4 + 2] cycloaddition reaction to approach a large acene with even-number linearly fused benzene rings: 6,9,16,19-tetraphenyl-1.20,4.5,10.11,14.15-tetrabenzooctatwistacene.

    PubMed

    Li, Junbo; Zhao, Yongbiao; Lu, Jing; Li, Gang; Zhang, Jingping; Zhao, Yang; Sun, Xiaowei; Zhang, Qichun

    2015-01-02

    It is more challenging to synthesize acenes with even-number fused benzene rings (AWEB) than acenes with odd-number fused benzene rings (AWOB) because AWEB are either synthetically asymmetric or the precursors to prepare AWEB are very difficult to obtain or to prepare from commercially available sources. In this work, we employed 2,6-naphthodiyne precursor (2) as an effective synthon to prepare a large AWEB, 6,9,16,19-tetraphenyl-1.20,4.5,10.11,14.15-tetrabenzooctatwistacene (1), through a simple, one-step, double [4 + 2] cycloaddition reaction. The physical properties of as-prepared octatwistacene (1) have been carefully studied, and the OLED performance of compound 1 was also investigated.

  15. Regio- and stereoselective synthesis of pregnane-fused isoxazolines by nitril-oxide/alkene 1,3-dipolar cycloaddition and an evaluation of their cell-growth inhibitory effect in vitro

    NASA Astrophysics Data System (ADS)

    Mótyán, Gergő; Baji, Ádám; Zupkó, István; Frank, Éva

    2016-04-01

    Efficient syntheses of some pregnane-fused isoxazolines from 16-dehydropregnenolone acetate with different arylnitrile oxides were carried out by 1,3-dipolar cycloadditions. The intermolecular ring-closures occurred in a highly regio- and stereoselective manner permitting the formation of a single 16α,17α-condensed diastereomer in which the O terminus of the nitrile oxide dipole is attached to C-17 of the sterane core. The conversions were found to be affected significantly by the electronic character of the substituents on the aromatic moiety of the 1,3-dipoles. Deacetylation of the primary products resulted in the corresponding 3β-OH analogs. All of the synthesized compounds were subjected to in vitro pharmacological studies for the determination of their antiproliferative effects on four breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361).

  16. Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

    PubMed

    Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

    2014-02-17

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) 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-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc 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.

  17. A Polyoxovanadate-Resorcin[4]arene-Based Porous Metal-Organic Framework as an Efficient Multifunctional Catalyst for the Cycloaddition of CO2 with Epoxides and the Selective Oxidation of Sulfides.

    PubMed

    Lu, Bing-Bing; Yang, Jin; Liu, Ying-Ying; Ma, Jian-Fang

    2017-10-02

    In this work, we report a new polyoxovanadate-resorcin[4]arene-based metal-organic framework (PMOF), [Co 2 L 0.5 V 4 O 12 ]·3DMF·5H 2 O (1), assembled with a newly functionalized wheel-like resorcin[4]arene ligand (L). 1 features an elegant porous motif and represents a rare example of PMOFs composed of both a resorcin[4]arene ligand and polyoxovanadate. Remarkably, 1 shows open V sites in the channel, which makes 1 an efficient heterogeneous Lewis acid catalyst for the cycloaddition of carbon dioxide to epoxides with high conversion and selectivity. Strikingly, 1 also exhibits high catalytic activity for the heterogeneous oxidative desulfurization of sulfides. Particularly, the heterogeneous catalyst 1 can be easily separated and reused with good catalytic activity.

  18. Full exploration of the Diels-Alder cycloaddition on metallofullerenes M3N@C80 (M = Sc, Lu, Gd): the D(5h) versus I(h) isomer and the influence of the metal cluster.

    PubMed

    Osuna, Sílvia; Valencia, Ramón; Rodríguez-Fortea, Antonio; Swart, Marcel; Solà, Miquel; Poblet, Josep M

    2012-07-16

    In this work a detailed investigation of the exohedral reactivity of the most important and abundant endohedral metallofullerene (EMF) is provided, that is, Sc(3)N@I(h)-C(80) and its D(5h) counterpart Sc(3)N@D(5h)-C(80) , and the (bio)chemically relevant lutetium- and gadolinium-based M(3)N@I(h)/D(5h)-C(80) EMFs (M = Sc, Lu, Gd). In particular, we analyze the thermodynamics and kinetics of the Diels-Alder cycloaddition of s-cis-1,3-butadiene on all the different bonds of the I(h)-C(80) and D(5h)-C(80) cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc(3)N@C(80). Afterwards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D(5h)-b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, I(h)-a, is the most reactive bond in M(3)N@D(5h)-C(80) regardless of M. Sc(3)N@C(80) and Lu(3)N@C(80) give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M = Gd, as previously found in similar metallofullerenes. Calculations also show that the D(5h) isomer is more reactive from the kinetic point of view than the I(h) one in all cases which is in good agreement with experiments. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis of 5-iodo-1,2,3-triazole-containing macrocycles using copper flow reactor technology.

    PubMed

    Bogdan, Andrew R; James, Keith

    2011-08-05

    A new macrocyclization strategy to synthesize 12- to 31-membered 5-iodo-1,2,3-triazole-containing macrocycles is described. The macrocycles have been generated using a simple and efficient copper-catalyzed cycloaddition in flow under environmentally friendly conditions. This methodology also permits the facile, regioselective synthesis of 1,4,5-trisubstituted-1,2,3-triazole-containing macrocyles using palladium-catalyzed cross-coupling reactions. © 2011 American Chemical Society

  20. Zinc-catalyzed allenylations of aldehydes and ketones.

    PubMed

    Fandrick, Daniel R; Saha, Jaideep; Fandrick, Keith R; Sanyal, Sanjit; Ogikubo, Junichi; Lee, Heewon; Roschangar, Frank; Song, Jinhua J; Senanayake, Chris H

    2011-10-21

    The general zinc-catalyzed allenylation of aldehydes and ketones with an allenyl boronate is presented. Preliminary mechanistic studies support a kinetically controlled process wherein, after a site-selective B/Zn exchange to generate a propargyl zinc intermediate, the addition to the electrophile effectively competes with propargyl-allenyl zinc equilibration. The utility of the methodology was demonstrated by application to a rhodium-catalyzed [4+2] cycloaddition. © 2011 American Chemical Society

  1. Extending the versatility of the Hemetsberger-Knittel indole synthesis through microwave and flow chemistry.

    PubMed

    Ranasinghe, Nadeesha; Jones, Graham B

    2013-03-15

    Microwave, flow and combination methodologies have been applied to the synthesis of a number of substituted indoles. Based on the Hemetsberger-Knittel (HK) process, modifications allow formation of products rapidly and in high yield. Adapting the methodology allows formation of 2-unsubstituted indoles and derivatives, and a route to analogs of the antitumor agent PLX-4032 is demonstrated. The utility of the HK substrates is further demonstrated through bioconjugation and subsequent ring closure and via Huisgen type [3+2] cycloaddition chemistry, allowing formation of peptide adducts which can be subsequently labeled with fluorine tags. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Catalysis of a 1,3-dipolar reaction by distorted DNA incorporating a heterobimetallic platinum(ii) and copper(ii) complex.

    PubMed

    Rivilla, Iván; de Cózar, Abel; Schäfer, Thomas; Hernandez, Frank J; Bittner, Alexander M; Eleta-Lopez, Aitziber; Aboudzadeh, Ali; Santos, José I; Miranda, José I; Cossío, Fernando P

    2017-10-01

    A novel catalytic system based on covalently modified DNA is described. This catalyst promotes 1,3-dipolar reactions between azomethine ylides and maleimides. The catalytic system is based on the distortion of the double helix of DNA by means of the formation of Pt(ii) adducts with guanine units. This distortion, similar to that generated in the interaction of DNA with platinum chemotherapeutic drugs, generates active sites that can accommodate N -metallated azomethine ylides. The proposed reaction mechanism, based on QM(DFT)/MM calculations, is compatible with thermally allowed concerted (but asynchronous) [π4s + π2s] mechanisms leading to the exclusive formation of racemic endo -cycloadducts.

  3. Catalysis of a 1,3-dipolar reaction by distorted DNA incorporating a heterobimetallic platinum(ii) and copper(ii) complex† †Electronic supplementary information (ESI) available: Experimental details, characterization of cycloadducts and intermediates, computational data. CCDC 1411372 and 1411373. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc02311a

    PubMed Central

    Rivilla, Iván; de Cózar, Abel; Schäfer, Thomas; Hernandez, Frank J.; Bittner, Alexander M.; Eleta-Lopez, Aitziber; Aboudzadeh, Ali; Santos, José I.; Miranda, José I.

    2017-01-01

    A novel catalytic system based on covalently modified DNA is described. This catalyst promotes 1,3-dipolar reactions between azomethine ylides and maleimides. The catalytic system is based on the distortion of the double helix of DNA by means of the formation of Pt(ii) adducts with guanine units. This distortion, similar to that generated in the interaction of DNA with platinum chemotherapeutic drugs, generates active sites that can accommodate N-metallated azomethine ylides. The proposed reaction mechanism, based on QM(DFT)/MM calculations, is compatible with thermally allowed concerted (but asynchronous) [π4s + π2s] mechanisms leading to the exclusive formation of racemic endo-cycloadducts. PMID:29147531

  4. HARNESSING THE CHEMISTRY OF CO{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Louie, Janis

    2012-11-30

    Our research presents several strategies for addressing the challenges of activating CO2. In addition, our cycloaddition chemistry addresses several fundamental issues pertaining to catalysis as it applies to energy conservation. Topics addressed include: DEVELOPMENT OF A CYCLOADDITION CATALYST; INCREASING THE UTILITY OF THE NI CYCLOADDITION CATALYST; UNDERSTANDING THE MECHANISM OF NI-CATALYZED CYCLOADDITION; and METAL-FREE CO{sub 2} ACTIVATION.

  5. Preparation of a new electro-optic polymer cross-linkable via copper-free thermal Huisgen cyclo-addition and fabrication of optical waveguides by Reactive Ion Etching.

    PubMed

    Cabanetos, Clément; Mahé, Hind; Blart, Errol; Pellegrin, Yann; Montembault, Véronique; Fontaine, Laurent; Adamietz, Frédéric; Rodriguez, Vincent; Bosc, Dominique; Odobel, Fabrice

    2011-06-01

    High-quality trails of ridge waveguides were successfully fabricated using a new cross-linkable polymer (PCC01) by UV photolithography followed by Reactive-Ion Etching (RIE) process. The cross-linking reaction of PCC01 is based on the copper-free Huisgen cyclo-addition between an azide and an acetylene group. The new cross-linkable polymer (PCC01) consists of a structural modification of the previously described materials (Scarpaci et al. Polym. Chem.2011, 2, 157), because the ethynyl group is functionalized by a methyl group instead of the TMS protecting group. This feature prevents the formation of silica (SiO(2)) generated by trimethylsilyl groups and which was stopping the engraving process before completion. Herein, we describe the synthesis, the NLO characterizations, and the fabrication of a high-quality ridge waveguide with PCC01. The new cross-linkable polymer PCC01 not only solves the problems encountered with our previously described polymers, but also presents an enhancement of the electro-optic stability, because d(33) coefficients up to 30 pm/V stable at 150 °C were recorded. © 2011 American Chemical Society

  6. Hydrosoluble Cu(i)-DAPTA complexes: synthesis, characterization, luminescence thermochromism and catalytic activity for microwave-assisted three-component azide-alkyne cycloaddition click reaction.

    PubMed

    Mahmoud, Abdallah G; Guedes da Silva, M Fátima C; Sokolnicki, Jerzy; Smoleński, Piotr; Pombeiro, Armando J L

    2018-05-16

    New hydrosoluble and air-stable Cu(i) halide compounds, viz. [CuX(DAPTA)3] (1) and (2), and [Cu(μ-X)(DAPTA)2]2 (3) and (4) (X = Br or I, in this order), have been prepared by reacting Cu(i) halide (i.e., bromide or iodide) with 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) under mild conditions. They represent the first examples of Cu(i) halide complexes bearing the DAPTA ligand, which have been fully characterized by elemental analysis, IR, 1H, 13C{1H} and 31P{1H} NMR spectroscopies, ESI-MS+ and, for 4, also by single-crystal X-ray diffraction (SCXRD) analyses. Complexes 1-4 are efficient catalysts for the one-pot microwave assisted three-component (terminal alkyne, organic halide and NaN3) Huisgen cycloaddition reaction in aqueous media to afford the corresponding disubstituted triazoles. The catalysis proceeds with a broad alkyne substrate scope and according to "click rules". Photophysical studies of compound 4 showed an unusual reversible thermochromic behaviour exhibiting a blue emission at 298 K due to the halide-to-ligand charge transfer (3XLCT) and a red emission at 77 K because of the {Cu2I2} unit.

  7. Rhodium(i)-catalyzed asymmetric [4 + 2] cycloaddition reactions of 2-alkylenecyclobutanols with cyclic enones through C–C bond cleavage: efficient access to trans-bicyclic compounds† †Electronic supplementary information (ESI) available. CCDC 1575240. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04784c

    PubMed Central

    Zheng, Xinxin; Guo, Rui

    2018-01-01

    We report a rhodium-catalyzed asymmetric formal intermolecular [4 + 2] cycloaddition reaction of 2-alkylenecyclobutanols with α,β-unsaturated cyclic ketones leading to synthetically useful trans-bicyclic molecules. Three consecutive stereogenic centers are formed in a highly enantio- and diastereoselective manner. Stepwise C–C bond cleavage and annulation are likely involved in the reaction pathway. Here, iPr-Duphos is the viable chiral ligand that promotes excellent enantio-control. PMID:29675233

  8. Kinetics and mechanics of photo-polymerized triazole-containing thermosetting composites via the copper(I)-catalyzed azide-alkyne cycloaddition

    PubMed Central

    Song, Han Byul; Wang, Xiance; Patton, James R.; Stansbury, Jeffrey W.; Bowman, Christopher N.

    2017-01-01

    Objectives Several features necessary for polymer composite materials in practical applications such as dental restorative materials were investigated in photo-curable CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition) thermosetting resin-based composites with varying filler loadings and compared to a conventional BisGMA/TEGDMA based composite. Methods Tri-functional alkyne and di-functional azide monomers were synthesized for CuAAC resins and incorporated with alkyne-functionalized silica microfillers for CuAAC composites. Polymerization kinetics, in situ temperature change, and shrinkage stress were monitored simultaneously with a tensometer coupled with FTIR spectroscopy and a data-logging thermocouple. The glass transition temperature was analyzed by dynamic mechanical analysis. Flexural modulus/strength and flexural toughness were characterized in three-point bending on a universal testing machine. Results The photo-CuAAC polymerization of composites containing between 0 and 60 wt% microfiller achieved ~99% conversion with a dramatic reduction in the maximum heat of reaction (~20 °C decrease) for the 60 wt% filled CuAAC composites as compared with the unfilled CuAAC resin. CuAAC composites with 60 wt% microfiller generated more than twice lower shrinkage stress of 0.43±0.01 MPa, equivalent flexural modulus of 6.1±0.7 GPa, equivalent flexural strength of 107±9 MPa, and more than 10 times higher energy absorption of 10±1 MJ m−3 when strained to 11% relative to BisGMA-based composites at equivalent filler loadings. Significance Mechanically robust and highly tough, photo-polymerized CuAAC composites with reduced shrinkage stress and a modest reaction exotherm were generated and resulted in essentially complete conversion. PMID:28363645

  9. Ferric Hydrogensulfate [Fe(HSO4)3] As a Reusable Heterogeneous Catalyst for the Synthesis of 5-Substituted-1H-Tetrazoles and Amides

    PubMed Central

    Eshghi, Hossein; Seyedi, Seyed Mohammad; Zarei, Elaheh Rahimi

    2011-01-01

    Ferric hydrogensulfate catalyzed the synthesis of 5-substituted 1H-tetrazoles via [2 + 3] cycloaddition of nitriles and sodium azide. This method has the advantages of high yields, simple methodology, and easy workup. The catalyst can be recovered by simple filtration and reused delivering good yields. Also, ferric hydrogensulfate catalyzed the hydrolysis of nitriles to primary amides under aqueous conditions. Various aliphatic and aromatic nitriles converted to the corresponding amides in good yields without any contamination with carboxylic acids. PMID:24052817

  10. Scalable, Stereocontrolled Total Syntheses of (±)–Axinellamines A and B

    PubMed Central

    Su, Shun; Rodriguez, Rodrigo A.; Baran, Phil S.

    2011-01-01

    The development of a simple, efficient, scalable, and stereocontrolled synthesis of a common intermediate en route to the axinellamines, massadines, and palau’amine is reported. This completely new route was utilized to prepare the axinellamines on a gram scale. In a more general sense, three distinct and enabling methodological advances were made during these studies: 1. ethylene glycol-assisted Pauson-Khand cycloaddition reaction, 2. a Zn/In-mediated Barbier type reaction, and 3. a TfNH2-assisted chlorination-spirocyclization. PMID:21846138

  11. Kinetics and mechanics of photo-polymerized triazole-containing thermosetting composites via the copper(I)-catalyzed azide-alkyne cycloaddition.

    PubMed

    Song, Han Byul; Wang, Xiance; Patton, James R; Stansbury, Jeffrey W; Bowman, Christopher N

    2017-06-01

    Several features necessary for polymer composite materials in practical applications such as dental restorative materials were investigated in photo-curable CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition) thermosetting resin-based composites with varying filler loadings and compared to a conventional BisGMA/TEGDMA based composite. Tri-functional alkyne and di-functional azide monomers were synthesized for CuAAC resins and incorporated with alkyne-functionalized glass microfillers for CuAAC composites. Polymerization kinetics, in situ temperature change, and shrinkage stress were monitored simultaneously with a tensometer coupled with FTIR spectroscopy and a data-logging thermocouple. The glass transition temperature was analyzed by dynamic mechanical analysis. Flexural modulus/strength and flexural toughness were characterized in three-point bending on a universal testing machine. The photo-CuAAC polymerization of composites containing between 0 and 60wt% microfiller achieved ∼99% conversion with a dramatic reduction in the maximum heat of reaction (∼20°C decrease) for the 60wt% filled CuAAC composites as compared with the unfilled CuAAC resin. CuAAC composites with 60wt% microfiller generated more than twice lower shrinkage stress of 0.43±0.01MPa, equivalent flexural modulus of 6.1±0.7GPa, equivalent flexural strength of 107±9MPa, and more than 10 times higher energy absorption of 10±1MJm -3 when strained to 11% relative to BisGMA-based composites at equivalent filler loadings. Mechanically robust and highly tough, photo-polymerized CuAAC composites with reduced shrinkage stress and a modest reaction exotherm were generated and resulted in essentially complete conversion. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  12. Payload training methodology study

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The results of the Payload Training Methodology Study (PTMS) are documented. Methods and procedures are defined for the development of payload training programs to be conducted at the Marshall Space Flight Center Payload Training Complex (PCT) for the Space Station Freedom program. The study outlines the overall training program concept as well as the six methodologies associated with the program implementation. The program concept outlines the entire payload training program from initial identification of training requirements to the development of detailed design specifications for simulators and instructional material. The following six methodologies are defined: (1) The Training and Simulation Needs Assessment Methodology; (2) The Simulation Approach Methodology; (3) The Simulation Definition Analysis Methodology; (4) The Simulator Requirements Standardization Methodology; (5) The Simulator Development Verification Methodology; and (6) The Simulator Validation Methodology.

  13. Rational Design Methodology.

    DTIC Science & Technology

    1978-09-01

    This report describes an effort to specify a software design methodology applicable to the Air Force software environment . Available methodologies...of techniques for proof of correctness, design specification, and performance assessment of static designs. The rational methodology selected is a

  14. Archetype modeling methodology.

    PubMed

    Moner, David; Maldonado, José Alberto; Robles, Montserrat

    2018-03-01

    Clinical Information Models (CIMs) expressed as archetypes play an essential role in the design and development of current Electronic Health Record (EHR) information structures. Although there exist many experiences about using archetypes in the literature, a comprehensive and formal methodology for archetype modeling does not exist. Having a modeling methodology is essential to develop quality archetypes, in order to guide the development of EHR systems and to allow the semantic interoperability of health data. In this work, an archetype modeling methodology is proposed. This paper describes its phases, the inputs and outputs of each phase, and the involved participants and tools. It also includes the description of the possible strategies to organize the modeling process. The proposed methodology is inspired by existing best practices of CIMs, software and ontology development. The methodology has been applied and evaluated in regional and national EHR projects. The application of the methodology provided useful feedback and improvements, and confirmed its advantages. The conclusion of this work is that having a formal methodology for archetype development facilitates the definition and adoption of interoperable archetypes, improves their quality, and facilitates their reuse among different information systems and EHR projects. Moreover, the proposed methodology can be also a reference for CIMs development using any other formalism. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Rh-Catalyzed Intermolecular Reactions of α-Alkyl-α-Diazo Carbonyl Compounds with Selectivity over β-Hydride Migration.

    PubMed

    DeAngelis, Andrew; Panish, Robert; Fox, Joseph M

    2016-01-19

    Rh-carbenes derived from α-diazocarbonyl compounds have found broad utility across a remarkable range of reactivity, including cyclopropanation, cyclopropenation, C-H insertions, heteroatom-hydrogen insertions, and ylide forming reactions. However, in contrast to α-aryl or α-vinyl-α-diazocarbonyl compounds, the utility of α-alkyl-α-diazocarbonyl compounds had been moderated by the propensity of such compounds to undergo intramolecular β-hydride migration to give alkene products. Especially challenging had been intermolecular reactions involving α-alkyl-α-diazocarbonyl compounds. This Account discusses the historical context and prior limitations of Rh-catalyzed reactions involving α-alkyl-α-diazocarbonyl compounds. Early studies demonstrated that ligand and temperature effects could influence chemoselectivity over β-hydride migration. However, effects were modest and conflicting conclusions had been drawn about the influence of sterically demanding ligands on β-hydride migration. More recent advances have led to a more detailed understanding of the reaction conditions that can promote intermolecular reactivity in preference to β-hydride migration. In particular, the use of bulky carboxylate ligands and low reaction temperatures have been key to enabling intermolecular cyclopropenation, cyclopropanation, carbonyl ylide formation/dipolar cycloaddition, indole C-H functionalization, and intramolecular bicyclobutanation with high chemoselectivity over β-hydride migration. Cyclic α-diazocarbonyl compounds have been shown to be particularly resilient toward β-hydride migration and are the first class of compounds that can engage in intermolecular reactivity in the presence of tertiary β-hydrogens. DFT calculations were used to propose that for cyclic α-diazocarbonyl compounds, ring constraints relieve steric interaction for intermolecular reactions and thereby accelerate the rate of intermolecular reactivity relative to intramolecular

  16. Fully recoverable rigid shape memory foam based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) using a salt leaching technique.

    PubMed

    Alzahrani, Abeer A; Saed, Mohand; Yakacki, Christopher M; Song, Han Byul; Sowan, Nancy; Walston, Joshua J; Shah, Parag K; McBride, Matthew K; Stansbury, Jeffrey W; Bowman, Christopher N

    2018-01-07

    This study is the first to employ the use of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) polymerization to form a tough and stiff, porous material from a well-defined network possessing a high glass transition temperature. The effect of the network linkages formed as a product of the CuAAC reaction, i.e., the triazoles, on the mechanical behavior at high strain was evaluated by comparing the CuAAC foam to an epoxy-amine-based foam, which consisted of monomers with similar backbone structures and mechanical properties (i.e., T g of 115 °C and a rubbery modulus of 1.0 MPa for the CuAAC foam, T g of 125 °C and a rubbery modulus of 1.2 MPa for the epoxy-amine foam). When each foam was compressed uniformly to 80% strain at ambient temperature, the epoxy-amine foam was severely damaged after only reaching 70% strain in the first compression cycle with a toughness of 300 MJ/m 3 . In contrast, the CuAAC foam exhibited pronounced ductile behavior in the glassy state with three times higher toughness of 850 MJ/m 3 after the first cycle of compression to 80% strain. Additionally, when the CuAAC foam was heated above T g after each of five compression cycles to 80% strain at ambient temperature, the foam completely recovered its original shape while exhibiting a gradual decrease in mechanical performance over the multiple compression cycles. The foam demonstrated almost complete shape fixity and recovery ratios even through five successive cycles, indicative of "reversible plasticity", making it highly desirable as a glassy shape memory foams.

  17. Methodological Gravitism

    ERIC Educational Resources Information Center

    Zaman, Muhammad

    2011-01-01

    In this paper the author presents the case of the exchange marriage system to delineate a model of methodological gravitism. Such a model is not a deviation from or alteration to the existing qualitative research approaches. I have adopted culturally specific methodology to investigate spouse selection in line with the Grounded Theory Method. This…

  18. Reliability Centered Maintenance - Methodologies

    NASA Technical Reports Server (NTRS)

    Kammerer, Catherine C.

    2009-01-01

    Journal article about Reliability Centered Maintenance (RCM) methodologies used by United Space Alliance, LLC (USA) in support of the Space Shuttle Program at Kennedy Space Center. The USA Reliability Centered Maintenance program differs from traditional RCM programs because various methodologies are utilized to take advantage of their respective strengths for each application. Based on operational experience, USA has customized the traditional RCM methodology into a streamlined lean logic path and has implemented the use of statistical tools to drive the process. USA RCM has integrated many of the L6S tools into both RCM methodologies. The tools utilized in the Measure, Analyze, and Improve phases of a Lean Six Sigma project lend themselves to application in the RCM process. All USA RCM methodologies meet the requirements defined in SAE JA 1011, Evaluation Criteria for Reliability-Centered Maintenance (RCM) Processes. The proposed article explores these methodologies.

  19. Rh(V) -Nitrenoid as a Key Intermediate in Rh(III) -Catalyzed Heterocyclization by C-H Activation: A Computational Perspective on the Cycloaddition of Benzamide and Diazo Compounds.

    PubMed

    Zhou, Tao; Guo, Wei; Xia, Yuanzhi

    2015-06-15

    A mechanistic study of the substituent-dependent ring formations in Rh(III) -catalyzed C-H activation/cycloaddition of benzamide and diazo compounds was carried out by using DFT calculations. The results indicated that the decomposition of the diazo is facilitated upon the formation of the five-membered rhodacycle, in which the Rh(III) center is more electrophilic. The insertion of carbenoid into Rh-C(phenyl) bond occurs readily and forms a 6-membered rhodacycle, however, the following C-N bond formation is difficult both kinetically and thermodynamically by reductive elimination from the Rh(III) species. Instead, the Rh(V) -nitrenoid intermediate could be formed by migration of the pivalate from N to Rh, which undergoes the heterocyclization much more easily and complementary ring-formations could be modulated by the nature of the substituent at the α-carbon. When a vinyl is attached, the stepwise 1,3-allylic migration occurs prior to the pivalate migration and the 8-membered ring product will be formed. On the other hand, the pivalate migration becomes more favorable for the phenyl-contained intermediate because of the difficult 1,3-allylic migration accompanied by dearomatization, thus the 5-membered ring product was formed selectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Situating methodology within qualitative research.

    PubMed

    Kramer-Kile, Marnie L

    2012-01-01

    Qualitative nurse researchers are required to make deliberate and sometimes complex methodological decisions about their work. Methodology in qualitative research is a comprehensive approach in which theory (ideas) and method (doing) are brought into close alignment. It can be difficult, at times, to understand the concept of methodology. The purpose of this research column is to: (1) define qualitative methodology; (2) illuminate the relationship between epistemology, ontology and methodology; (3) explicate the connection between theory and method in qualitative research design; and 4) highlight relevant examples of methodological decisions made within cardiovascular nursing research. Although there is no "one set way" to do qualitative research, all qualitative researchers should account for the choices they make throughout the research process and articulate their methodological decision-making along the way.

  1. A 26-Membered Macrocycle Obtained by a Double Diels-Alder Cycloaddition Between Two 2H-Pyran-2-one Rings and Two 1,1'-(Hexane-1,6-diyl)bis (1H-pyrrole-2,5-dione)s.

    PubMed

    Turek, Bor Lucijan; Kočevar, Marijan; Kranjc, Krištof; Perdih, Franc

    2017-12-01

    With the application of a double dienophile 1,1'-(hexane-1,6-diyl)bis(1H-pyrrole-2,5-dione) for a [4+2] cycloaddition with a substituted 2H-pyran-2-one a novel 26-membered tetraaza heteromacrocyclic system 3 was prepared via a direct method under solvent-free conditions with microwave irradiation. The macrocycle prepared is composed of two units of the dienophile and two of the diene. The structure of the macrocycle was characterized on the basis of IR, 1H and 13C NMR and mass spectroscopy, as well as by the elemental analysis and melting point determination. With X-ray diffraction of a single crystal of the macrocycle we have determined that the two acetyl groups (attached to the bridging double bond of the bicyclo[2.2.2]octene fragments) are oriented towards each other (and also towards the inside of the cavity of the macrocycle), therefore, mostly filling it completely.

  2. Natural Diels-Alderases: Elusive and Irresistable

    PubMed Central

    Klas, Kimberly; Tsukamoto, Sachiko; Sherman, David H.; Williams, Robert M.

    2016-01-01

    Eight examples of biosynthetic pathways wherein a natural enzyme has been identified and claimed to function as a catalyst for the [4+2] cycloaddition reaction, namely, Diels-Alderases, are briefly reviewed. These are discussed in the context of the mechanistic challenges associated with the technical difficulty of proving that the net formal [4+2] cycloaddition under study, indeed proceeds through a synchronous, mechanism and that the putative biosynthetic enzyme deploys the pericyclic transition state required for a Diels-Alder cycloaddition reaction. PMID:26495876

  3. Experimental Investigation on the Mechanism of Chelation-Assisted, Copper(II) Acetate-Accelerated Azide-Alkyne Cycloaddition

    PubMed Central

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

    2011-01-01

    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 1H NMR assays are developed for monitoring the reaction progress in two different solvents – methanol and acetonitrile. Solvent kinetic isotopic effect and pre-mixing 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

  4. Kaupapa Maori Methodology: Trusting the Methodology through Thick and Thin

    ERIC Educational Resources Information Center

    Hiha, Anne Aroha

    2016-01-01

    Kaupapa Maori is thoroughly theorised in academia in Aotearoa and those wishing to use it as their research methodology can find support through the writing of a number of Maori academics. What is not so well articulated, is the experiential voice of those who have used Kaupapa Maori as research methodology. My identity as a Maori woman…

  5. The thriving chemistry of ketenimines.

    PubMed

    Lu, Ping; Wang, Yanguang

    2012-09-07

    Ketenimines are an important class of reactive species and useful synthetic intermediates. During the last two decades several practical and versatile approaches to ketenimines have been developed, leading to exhaustive investigations on ketenimine chemistry and the discovery of a variety of highly efficient reactions. Five types of reactions for ketenimines have been reported, including nucleophilic additions (ketenimines can be used as both electrophiles and nucleophiles), radical additions, cycloaddition reactions, electrocyclic ring closure reactions, and σ rearrangements. Furthermore, numerous complex organic compounds, particularly the biologically interesting heterocycles, have been constructed using these methodologies. The review of these accomplishments is presented here.

  6. Feminist methodologies and engineering education research

    NASA Astrophysics Data System (ADS)

    Beddoes, Kacey

    2013-03-01

    This paper introduces feminist methodologies in the context of engineering education research. It builds upon other recent methodology articles in engineering education journals and presents feminist research methodologies as a concrete engineering education setting in which to explore the connections between epistemology, methodology and theory. The paper begins with a literature review that covers a broad range of topics featured in the literature on feminist methodologies. Next, data from interviews with engineering educators and researchers who have engaged with feminist methodologies are presented. The ways in which feminist methodologies shape their research topics, questions, frameworks of analysis, methods, practices and reporting are each discussed. The challenges and barriers they have faced are then discussed. Finally, the benefits of further and broader engagement with feminist methodologies within the engineering education community are identified.

  7. Feminist Methodologies and Engineering Education Research

    ERIC Educational Resources Information Center

    Beddoes, Kacey

    2013-01-01

    This paper introduces feminist methodologies in the context of engineering education research. It builds upon other recent methodology articles in engineering education journals and presents feminist research methodologies as a concrete engineering education setting in which to explore the connections between epistemology, methodology and theory.…

  8. The rhodium catalyzed three-component reaction of diazoacetates, titanium(IV) alkoxides and aldehydes.

    PubMed

    Lu, Chong-Dao; Liu, Hui; Chen, Zhi-Yong; Hu, Wen-Hao; Mi, Ai-Qiao

    2005-05-28

    The rhodium(II)-catalyzed three-component reaction of diazoacetates, titanium alkoxides and aldehydes is shown to give alpha-alkoxyl-beta-hydroxyl acid derivatives; the novel C-C bond formation reaction is proposed to occur through oxonium ylides derived from diazo compounds and titanium alkoxides, and followed by intermolecular trapping by aldehydes.

  9. Carbon-hydrogen bond activation, C-N bond coupling, and cycloaddition reactivity of a three-coordinate nickel complex featuring a terminal imido ligand.

    PubMed

    Mindiola, Daniel J; Waterman, Rory; Iluc, Vlad M; Cundari, Thomas R; Hillhouse, Gregory L

    2014-12-15

    The three-coordinate imidos (dtbpe)Ni═NR (dtbpe = (t)Bu2PCH2CH2P(t)Bu2, R = 2,6-(i)Pr2C6H3, 2,4,6-Me3C6H2 (Mes), and 1-adamantyl (Ad)), which contain a legitimate Ni-N double bond as well as basic imido nitrogen based on theoretical analysis, readily deprotonate HC≡CPh to form the amide acetylide species (dtbpe)Ni{NH(Ar)}(C≡CPh). In the case of R = 2,6-(i)Pr2C6H3, reductive carbonylation results in formation of the (dtbpe)Ni(CO)2 along with the N-C coupled product keteneimine PhCH═C═N(2,6- (i)Pr2C6H3). Given the ability of the Ni═N bond to have biradical character as suggested by theoretical analysis, H atom abstraction can also occur in (dtbpe)Ni═N{2,6-(i)Pr2C6H3} when this species is treated with HSn((n)Bu)3. Likewise, the microscopic reverse reaction--conversion of the Ni(I) anilide (dtbpe)Ni{NH(2,6-(i)Pr2C6H3)} to the imido (dtbpe)Ni═N{2,6-(i)Pr2C6H3}--is promoted when using the radical Mes*O(•) (Mes* = 2,4,6-(t)Bu3C6H2). Reactivity studies involving the imido complexes, in particular (dtbpe)Ni═N{2,6-(i)Pr2C6H3}, are also reported with small, unsaturated molecules such as diphenylketene, benzylisocyanate, benzaldehyde, and carbon dioxide, including the formation of C-N and N-N bonds by coupling reactions. In addition to NMR spectroscopic data and combustion analysis, we also report structural studies for all the cycloaddition reactions involving the imido (dtbpe)Ni═N{2,6-(i)Pr2C6H3}.

  10. Carbon–Hydrogen Bond Activation, C–N Bond Coupling, and Cycloaddition Reactivity of a Three-Coordinate Nickel Complex Featuring a Terminal Imido Ligand

    PubMed Central

    2015-01-01

    The three-coordinate imidos (dtbpe)Ni=NR (dtbpe = tBu2PCH2CH2PtBu2, R = 2,6-iPr2C6H3, 2,4,6-Me3C6H2 (Mes), and 1-adamantyl (Ad)), which contain a legitimate Ni–N double bond as well as basic imido nitrogen based on theoretical analysis, readily deprotonate HC≡CPh to form the amide acetylide species (dtbpe)Ni{NH(Ar)}(C≡CPh). In the case of R = 2,6-iPr2C6H3, reductive carbonylation results in formation of the (dtbpe)Ni(CO)2 along with the N–C coupled product keteneimine PhCH=C=N(2,6- iPr2C6H3). Given the ability of the Ni=N bond to have biradical character as suggested by theoretical analysis, H atom abstraction can also occur in (dtbpe)Ni=N{2,6-iPr2C6H3} when this species is treated with HSn(nBu)3. Likewise, the microscopic reverse reaction—conversion of the Ni(I) anilide (dtbpe)Ni{NH(2,6-iPr2C6H3)} to the imido (dtbpe)Ni=N{2,6-iPr2C6H3}—is promoted when using the radical Mes*O• (Mes* = 2,4,6-tBu3C6H2). Reactivity studies involving the imido complexes, in particular (dtbpe)Ni=N{2,6-iPr2C6H3}, are also reported with small, unsaturated molecules such as diphenylketene, benzylisocyanate, benzaldehyde, and carbon dioxide, including the formation of C–N and N–N bonds by coupling reactions. In addition to NMR spectroscopic data and combustion analysis, we also report structural studies for all the cycloaddition reactions involving the imido (dtbpe)Ni=N{2,6-iPr2C6H3}. PMID:25437507

  11. Regional Shelter Analysis Methodology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dillon, Michael B.; Dennison, Deborah; Kane, Jave

    2015-08-01

    The fallout from a nuclear explosion has the potential to injure or kill 100,000 or more people through exposure to external gamma (fallout) radiation. Existing buildings can reduce radiation exposure by placing material between fallout particles and exposed people. Lawrence Livermore National Laboratory was tasked with developing an operationally feasible methodology that could improve fallout casualty estimates. The methodology, called a Regional Shelter Analysis, combines the fallout protection that existing buildings provide civilian populations with the distribution of people in various locations. The Regional Shelter Analysis method allows the consideration of (a) multiple building types and locations within buildings, (b)more » country specific estimates, (c) population posture (e.g., unwarned vs. minimally warned), and (d) the time of day (e.g., night vs. day). The protection estimates can be combined with fallout predictions (or measurements) to (a) provide a more accurate assessment of exposure and injury and (b) evaluate the effectiveness of various casualty mitigation strategies. This report describes the Regional Shelter Analysis methodology, highlights key operational aspects (including demonstrating that the methodology is compatible with current tools), illustrates how to implement the methodology, and provides suggestions for future work.« less

  12. Review of PCR methodology.

    DOT National Transportation Integrated Search

    1998-03-01

    This study was conducted to review the Pavement Condition Rating (PCR) : methodology currently used by the Ohio DOT. The results of the literature search in this : connection indicated that many Highway agencies use a similar methodology to rate thei...

  13. Methodological challenges to human medical study.

    PubMed

    Zhong, Yixin; Liu, Baoyan; Qu, Hua; Xie, Qi

    2014-09-01

    With the transformation of modern medicinal pattern, medical studies are confronted with methodological challenges. By analyzing two methodologies existing in the study of physical matter system and information system, the article points out that traditional Chinese medicine (TCM), especially the treatment based on syndrome differentiation, embodies information conception of methodological positions, while western medicine represents matter conception of methodological positions. It proposes a new way of thinking about combination of TCM and western medicine by combinating two kinds of methodological methods.

  14. H2O-Polyaluminium chloride-TBAB as synergistic catalysts for the synthesis of cyclic carbonate

    NASA Astrophysics Data System (ADS)

    Liu, X. J.; Yan, P.; Han, Y.

    2018-01-01

    An efficient catalytic system consisting of H2O, Polyaluminium chloride (PAC) and Tetrabutylammonium bromide (TBAB) was applied to the cycloaddition of carbon dioxide (CO2) to epoxides under mild conditions. Their catalytic cycloaddition activities were found to be well correlated with H2O and polyaluminium chloride, which had a synergetic effect with the halide anion of TBAB. The presence of H2O and PAC could remarkably improve the yield of propylene carbonate (PC) by which the reaction yield is about 4-5 times higher than TBAB. alone.The catalytic system also exhibited excellent cycloaddition activities for various epoxide substrates.

  15. The Methodology of Magpies

    ERIC Educational Resources Information Center

    Carter, Susan

    2014-01-01

    Arts/Humanities researchers frequently do not explain methodology overtly; instead, they "perform" it through their use of language, textual and historic cross-reference, and theory. Here, methodologies from literary studies are shown to add to Higher Education (HE) an exegetical and critically pluralist approach. This includes…

  16. Data Centric Development Methodology

    ERIC Educational Resources Information Center

    Khoury, Fadi E.

    2012-01-01

    Data centric applications, an important effort of software development in large organizations, have been mostly adopting a software methodology, such as a waterfall or Rational Unified Process, as the framework for its development. These methodologies could work on structural, procedural, or object oriented based applications, but fails to capture…

  17. Consecutive three-component synthesis of (hetero)arylated propargyl amides by chemoenzymatic aminolysis-Sonogashira coupling sequence.

    PubMed

    Hassan, Sidra; Ullrich, Anja; Müller, Thomas J J

    2015-02-07

    A novel chemoenzymatic three-component synthesis of (hetero)arylated propargyl amides in good yields based upon Novozyme® 435 (Candida antarctica lipase B (CAL-B)) catalyzed aminolysis of methyl carboxylates followed by Sonogashira coupling with (hetero)aryliodides in a consecutive one-pot fashion has been presented. This efficient methodology can be readily concatenated with a CuAAC (Cu catalyzed alkyne azide cycloaddition) as a third consecutive step to furnish 1,4-disubstituted 1,2,3-triazole ligated arylated propargyl amides. This one-pot process can be regarded as a transition metal catalyzed sequence that takes advantage of the copper source still present from the cross-coupling step.

  18. Suggested criteria for evaluating systems engineering methodologies

    NASA Technical Reports Server (NTRS)

    Gates, Audrey; Paul, Arthur S.; Gill, Tepper L.

    1989-01-01

    Systems engineering is the application of mathematical and scientific principles to practical ends in the life-cycle of a system. A methodology for systems engineering is a carefully developed, relatively complex procedure or process for applying these mathematical and scientific principles. There are many systems engineering methodologies (or possibly many versions of a few methodologies) currently in use in government and industry. These methodologies are usually designed to meet the needs of a particular organization. It has been observed, however, that many technical and non-technical problems arise when inadequate systems engineering methodologies are applied by organizations to their systems development projects. Various criteria for evaluating systems engineering methodologies are discussed. Such criteria are developed to assist methodology-users in identifying and selecting methodologies that best fit the needs of the organization.

  19. Menopause and Methodological Doubt

    ERIC Educational Resources Information Center

    Spence, Sheila

    2005-01-01

    Menopause and methodological doubt begins by making a tongue-in-cheek comparison between Descartes' methodological doubt and the self-doubt that can arise around menopause. A hermeneutic approach is taken in which Cartesian dualism and its implications for the way women are viewed in society are examined, both through the experiences of women…

  20. Information technology security system engineering methodology

    NASA Technical Reports Server (NTRS)

    Childs, D.

    2003-01-01

    A methodology is described for system engineering security into large information technology systems under development. The methodology is an integration of a risk management process and a generic system development life cycle process. The methodology is to be used by Security System Engineers to effectively engineer and integrate information technology security into a target system as it progresses through the development life cycle. The methodology can also be used to re-engineer security into a legacy system.

  1. A Computational Experiment of the Endo versus Exo Preference in a Diels-Alder Reaction

    ERIC Educational Resources Information Center

    Rowley, Christopher N.; Woo, Tom K.

    2009-01-01

    We have developed and tested a computational laboratory that investigates an endo versus exo Diels-Alder cycloaddition. This laboratory employed density functional theory (DFT) calculations to study the cycloaddition of N-phenylmaleimide to furan. The endo and exo stereoisomers of the product were distinguished by building the two isomers in a…

  2. A Critique of Methodological Dualism in Education

    ERIC Educational Resources Information Center

    Yang, Jeong A.; Yoo, Jae-Bong

    2018-01-01

    This paper aims to critically examine the paradigm of methodological dualism and explore whether methodologies in social science currently are appropriate for educational research. There are two primary methodologies for studying education: quantitative and qualitative methods. This is what we mean by "methodological dualism". Is…

  3. Q methodology in health economics.

    PubMed

    Baker, Rachel; Thompson, Carl; Mannion, Russell

    2006-01-01

    The recognition that health economists need to understand the meaning of data if they are to adequately understand research findings which challenge conventional economic theory has led to the growth of qualitative modes of enquiry in health economics. The use of qualitative methods of exploration and description alongside quantitative techniques gives rise to a number of epistemological, ontological and methodological challenges: difficulties in accounting for subjectivity in choices, the need for rigour and transparency in method, and problems of disciplinary acceptability to health economists. Q methodology is introduced as a means of overcoming some of these challenges. We argue that Q offers a means of exploring subjectivity, beliefs and values while retaining the transparency, rigour and mathematical underpinnings of quantitative techniques. The various stages of Q methodological enquiry are outlined alongside potential areas of application in health economics, before discussing the strengths and limitations of the approach. We conclude that Q methodology is a useful addition to economists' methodological armoury and one that merits further consideration and evaluation in the study of health services.

  4. 10 CFR 436.14 - Methodological assumptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Methodological assumptions. 436.14 Section 436.14 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.14 Methodological assumptions. (a) Each Federal Agency shall...

  5. 10 CFR 436.14 - Methodological assumptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Methodological assumptions. 436.14 Section 436.14 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.14 Methodological assumptions. (a) Each Federal Agency shall...

  6. 10 CFR 436.14 - Methodological assumptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Methodological assumptions. 436.14 Section 436.14 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.14 Methodological assumptions. (a) Each Federal Agency shall...

  7. 10 CFR 436.14 - Methodological assumptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Methodological assumptions. 436.14 Section 436.14 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.14 Methodological assumptions. (a) Each Federal Agency shall...

  8. 10 CFR 436.14 - Methodological assumptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Methodological assumptions. 436.14 Section 436.14 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.14 Methodological assumptions. (a) Each Federal Agency shall...

  9. Thoughts on an Indigenous Research Methodology.

    ERIC Educational Resources Information Center

    Steinhauer, Evelyn

    2002-01-01

    Reviews writings of Indigenous scholars concerning the need for and nature of an Indigenous research methodology. Discusses why an Indigenous research methodology is needed; the importance of relational accountability in such a methodology; why Indigenous people must conduct Indigenous research; Indigenous knowledge and ways of knowing (including…

  10. C–H Functionalization of Cyclic Amines: Redox-Annulations with α,β-Unsaturated Carbonyl Compounds

    PubMed Central

    Kang, YoungKu; Richers, Matthew T.; Sawicki, Conrad H.; Seidel, Daniel

    2015-01-01

    Cyclic amines such as pyrrolidine and 1,2,3,4-tetrahydroisoquinoline undergo redox-annulations with α,β-unsaturated aldehydes and ketones. Carboxylic acid promoted generation of a conjugated azomethine ylide is followed by 6π-electrocylization, and, in some cases, tautomerization. The resulting ring-fused pyrrolines are readily oxidized to the corresponding pyrroles or reduced to pyrrolidines. PMID:26051897

  11. Prioritization Methodology for Chemical Replacement

    NASA Technical Reports Server (NTRS)

    Cruit, W.; Schutzenhofer, S.; Goldberg, B.; Everhart, K.

    1993-01-01

    This project serves to define an appropriate methodology for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weigh the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results are being implemented as a guideline for consideration for current NASA propulsion systems.

  12. 42 CFR 441.472 - Budget methodology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Budget methodology. 441.472 Section 441.472 Public... Self-Directed Personal Assistance Services Program § 441.472 Budget methodology. (a) The State shall set forth a budget methodology that ensures service authorization resides with the State and meets the...

  13. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

    1995-01-01

    This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

  14. Synthesis of 1-octacosanol and GC-C-IRMS discrimination of samples from different origin.

    PubMed

    Cravotto, Giancarlo; Calcio Gaudino, Emanuela; Barge, Alessandro; Binello, Arianna; Albertino, Andrea; Aghemo, Costanza

    2010-03-01

    Lately, long-chain primary alcohols have been investigated in depth on account of their biological activities. In particular, 1-octacosanol (C(28)H(57)OH), the main component of policosanol, the hypolipidaemic fatty alcohol mixture obtained from sugar cane wax, has been the subject of a multitude of pharmacological studies. The aim of this work was to search a convenient synthetic protocol for the preparation of 1-octacosanol in a gram scale. The key step was a Wittig reaction between the octadecyltriphenylphosphonium ylide and the methyl 10-oxodecanoate. Some steps were further improved by power ultrasound and microwave irradiation, either alone or in combination. Our methodology is suitable for a rapid generation of homologues by varying the chain length in the alkyl halide. Due to the high commercial value, a series of 1-octacosanol samples, either isolated from natural sources or from synthesis (different origin and suppliers), were analysed by gas chromatography-combustion-isotopic ratio mass spectrometry (GC-C-IRMS) and according to the carbon isotopic content, classified on the basis of their origin.

  15. A Brief Introduction to Q Methodology

    ERIC Educational Resources Information Center

    Yang, Yang

    2016-01-01

    Q methodology is a method to systematically study subjective matters such as thoughts and beliefs on any given topic. Q methodology can be used for both theory building and theory testing. The purpose of this paper was to give a brief overview of Q methodology to readers with various backgrounds. This paper discussed several advantages of Q…

  16. Methodological issues of genetic association studies.

    PubMed

    Simundic, Ana-Maria

    2010-12-01

    Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

  17. Which Methodology Works Better? English Language Teachers' Awareness of the Innovative Language Learning Methodologies

    ERIC Educational Resources Information Center

    Kurt, Mustafa

    2015-01-01

    The present study investigated whether English language teachers were aware of the innovative language learning methodologies in language learning, how they made use of these methodologies and the learners' reactions to them. The descriptive survey method was employed to disclose the frequencies and percentages of 175 English language teachers'…

  18. Carbon–hydrogen bond activation, C–N bond coupling, and cycloaddition reactivity of a three-coordinate nickel complex featuring a terminal imido ligand

    DOE PAGES

    Mindiola, Daniel J.; Waterman, Rory; Iluc, Vlad M.; ...

    2014-12-01

    Here, the three-coordinate imidos (dtbpe)Ni=NR (dtbpe = tBu 2PCH 2CH 2PtBu 2, R = 2,6- iPr 2C 6H 3, 2,4,6-Me 3C 6H 2 (Mes), and 1-adamantyl (Ad)), which contain a legitimate Ni–N double bond as well as basic imido nitrogen based on theoretical analysis, readily deprotonate HC≡CPh to form the amide acetylide species (dtbpe)Ni{NH(Ar)}(C≡CPh). In the case of R = 2,6- iPr 2C 6H 3, reductive carbonylation results in formation of the (dtbpe)Ni(CO) 2 along with the N–C coupled product keteneimine PhCH=C=N(2,6- iPr 2C 6H 3). Given the ability of the Ni=N bond to have biradical character as suggested bymore » theoretical analysis, H atom abstraction can also occur in (dtbpe)Ni=N{2,6- iPr 2C 6H 3} when this species is treated with HSn( nBu) 3. Likewise, the microscopic reverse reaction—conversion of the Ni(I) anilide (dtbpe)Ni{NH(2,6- iPr 2C 6H 3)} to the imido (dtbpe)Ni=N{2,6- iPr 2C 6H 3}—is promoted when using the radical Mes*O • (Mes* = 2,4,6- tBu 3C 6H 2). Reactivity studies involving the imido complexes, in particular (dtbpe)Ni=N{2,6- iPr 2C 6H 3}, are also reported with small, unsaturated molecules such as diphenylketene, benzylisocyanate, benzaldehyde, and carbon dioxide, including the formation of C–N and N–N bonds by coupling reactions. In addition to NMR spectroscopic data and combustion analysis, we also report structural studies for all the cycloaddition reactions involving the imido (dtbpe)Ni=N{2,6- iPr 2C 6H 3}.« less

  19. Carbon–hydrogen bond activation, C–N bond coupling, and cycloaddition reactivity of a three-coordinate nickel complex featuring a terminal imido ligand

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mindiola, Daniel J.; Waterman, Rory; Iluc, Vlad M.

    Here, the three-coordinate imidos (dtbpe)Ni=NR (dtbpe = tBu 2PCH 2CH 2PtBu 2, R = 2,6- iPr 2C 6H 3, 2,4,6-Me 3C 6H 2 (Mes), and 1-adamantyl (Ad)), which contain a legitimate Ni–N double bond as well as basic imido nitrogen based on theoretical analysis, readily deprotonate HC≡CPh to form the amide acetylide species (dtbpe)Ni{NH(Ar)}(C≡CPh). In the case of R = 2,6- iPr 2C 6H 3, reductive carbonylation results in formation of the (dtbpe)Ni(CO) 2 along with the N–C coupled product keteneimine PhCH=C=N(2,6- iPr 2C 6H 3). Given the ability of the Ni=N bond to have biradical character as suggested bymore » theoretical analysis, H atom abstraction can also occur in (dtbpe)Ni=N{2,6- iPr 2C 6H 3} when this species is treated with HSn( nBu) 3. Likewise, the microscopic reverse reaction—conversion of the Ni(I) anilide (dtbpe)Ni{NH(2,6- iPr 2C 6H 3)} to the imido (dtbpe)Ni=N{2,6- iPr 2C 6H 3}—is promoted when using the radical Mes*O • (Mes* = 2,4,6- tBu 3C 6H 2). Reactivity studies involving the imido complexes, in particular (dtbpe)Ni=N{2,6- iPr 2C 6H 3}, are also reported with small, unsaturated molecules such as diphenylketene, benzylisocyanate, benzaldehyde, and carbon dioxide, including the formation of C–N and N–N bonds by coupling reactions. In addition to NMR spectroscopic data and combustion analysis, we also report structural studies for all the cycloaddition reactions involving the imido (dtbpe)Ni=N{2,6- iPr 2C 6H 3}.« less

  20. Security Quality Requirements Engineering (SQUARE) Methodology

    DTIC Science & Technology

    2005-11-01

    such as Joint Application Development and the Accelerated Requirements Method [Wood 89, Hubbard 99] • Soft Systems Methodology [Checkland 89...investigated were misuse cases [Jacobson 92], Soft Systems Methodology (SSM) [Checkland 89], Quality Function Deployment (QFD) [QFD 05], Con- trolled...html (2005). [Checkland 89] Checkland, Peter. Soft Systems Methodology . Rational Analysis for a Problematic World. New York, NY: John Wiley & Sons

  1. Environmental probabilistic quantitative assessment methodologies

    USGS Publications Warehouse

    Crovelli, R.A.

    1995-01-01

    In this paper, four petroleum resource assessment methodologies are presented as possible pollution assessment methodologies, even though petroleum as a resource is desirable, whereas pollution is undesirable. A methodology is defined in this paper to consist of a probability model and a probabilistic method, where the method is used to solve the model. The following four basic types of probability models are considered: 1) direct assessment, 2) accumulation size, 3) volumetric yield, and 4) reservoir engineering. Three of the four petroleum resource assessment methodologies were written as microcomputer systems, viz. TRIAGG for direct assessment, APRAS for accumulation size, and FASPU for reservoir engineering. A fourth microcomputer system termed PROBDIST supports the three assessment systems. The three assessment systems have different probability models but the same type of probabilistic method. The type of advantages of the analytic method are in computational speed and flexibility, making it ideal for a microcomputer. -from Author

  2. UNICORN (Version III) Methodology.

    DTIC Science & Technology

    1976-10-01

    rAD-A124 766 UNICORN CYERSION’III) NETHODOLOGYMU SCIENCE / APPLICATIONS INC ENGLEWOOD CO L M BLACKWELL ET AL. OCT 76 SAI-76-648-DEN DCAII-75-C-802...1ii4 4% 83 02 010GZ SAI-76-048-DEN .. UNICORN (VERSION III) METHODOLOGY TECHNICAL MEMORANDUM by core L. M. Blackwell . IF’l 4 H. E. Hock T. A. Kriz D...6 DISCUSSION .. ... ..... ..... ..... ..... ...... 7 FINDINGS AND CONCLUSIONS--THE UNICORN METHODOLOGY .. .. ... ..... 9

  3. [Radiotherapy phase I trials' methodology: Features].

    PubMed

    Rivoirard, R; Vallard, A; Langrand-Escure, J; Guy, J-B; Ben Mrad, M; Yaoxiong, X; Diao, P; Méry, B; Pigne, G; Rancoule, C; Magné, N

    2016-12-01

    In clinical research, biostatistical methods allow the rigorous analysis of data collection and should be defined from the trial design to obtain the appropriate experimental approach. Thus, if the main purpose of phase I is to determine the dose to use during phase II, methodology should be finely adjusted to experimental treatment(s). Today, the methodology for chemotherapy and targeted therapy is well known. For radiotherapy and chemoradiotherapy phase I trials, the primary endpoint must reflect both effectiveness and potential treatment toxicities. Methodology should probably be complex to limit failures in the following phases. However, there are very few data about methodology design in the literature. The present study focuses on these particular trials and their characteristics. It should help to raise existing methodological patterns shortcomings in order to propose new and better-suited designs. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  4. Multifunctional Mesoporous Ionic Gels and Scaffolds Derived from Polyhedral Oligomeric Silsesquioxanes.

    PubMed

    Lee, Jin Hong; Lee, Albert S; Lee, Jong-Chan; Hong, Soon Man; Hwang, Seung Sang; Koo, Chong Min

    2017-02-01

    A new methodology for fabrication of inorganic-organic hybrid ionogels and scaffolds is developed through facile cross-linking and solution extraction of a newly developed ionic polyhedral oligomeric silsesquioxane with inorganic core. Through design of various cationic tertiary amines, as well as cross-linkable functional groups on each arm of the inorganic core, high-performance ionogels are fabricated with excellent electrochemical stability and unique ion conduction behavior, giving superior lithium ion battery performance. Moreover, through solvent extraction of the liquid components, hybrid scaffolds with well-defined, interconnected mesopores are utilized as heterogeneous catalysts for the CO 2 -catalyzed cycloaddition of epoxides. Excellent catalytic performance, as well as highly efficient recyclability are observed when compared to other previous literature materials.

  5. Workshops as a Research Methodology

    ERIC Educational Resources Information Center

    Ørngreen, Rikke; Levinsen, Karin

    2017-01-01

    This paper contributes to knowledge on workshops as a research methodology, and specifically on how such workshops pertain to e-learning. A literature review illustrated that workshops are discussed according to three different perspectives: workshops as a means, workshops as practice, and workshops as a research methodology. Focusing primarily on…

  6. Reliability based design optimization: Formulations and methodologies

    NASA Astrophysics Data System (ADS)

    Agarwal, Harish

    Modern products ranging from simple components to complex systems should be designed to be optimal and reliable. The challenge of modern engineering is to ensure that manufacturing costs are reduced and design cycle times are minimized while achieving requirements for performance and reliability. If the market for the product is competitive, improved quality and reliability can generate very strong competitive advantages. Simulation based design plays an important role in designing almost any kind of automotive, aerospace, and consumer products under these competitive conditions. Single discipline simulations used for analysis are being coupled together to create complex coupled simulation tools. This investigation focuses on the development of efficient and robust methodologies for reliability based design optimization in a simulation based design environment. Original contributions of this research are the development of a novel efficient and robust unilevel methodology for reliability based design optimization, the development of an innovative decoupled reliability based design optimization methodology, the application of homotopy techniques in unilevel reliability based design optimization methodology, and the development of a new framework for reliability based design optimization under epistemic uncertainty. The unilevel methodology for reliability based design optimization is shown to be mathematically equivalent to the traditional nested formulation. Numerical test problems show that the unilevel methodology can reduce computational cost by at least 50% as compared to the nested approach. The decoupled reliability based design optimization methodology is an approximate technique to obtain consistent reliable designs at lesser computational expense. Test problems show that the methodology is computationally efficient compared to the nested approach. A framework for performing reliability based design optimization under epistemic uncertainty is also developed

  7. USGS Methodology for Assessing Continuous Petroleum Resources

    USGS Publications Warehouse

    Charpentier, Ronald R.; Cook, Troy A.

    2011-01-01

    The U.S. Geological Survey (USGS) has developed a new quantitative methodology for assessing resources in continuous (unconventional) petroleum deposits. Continuous petroleum resources include shale gas, coalbed gas, and other oil and gas deposits in low-permeability ("tight") reservoirs. The methodology is based on an approach combining geologic understanding with well productivities. The methodology is probabilistic, with both input and output variables as probability distributions, and uses Monte Carlo simulation to calculate the estimates. The new methodology is an improvement of previous USGS methodologies in that it better accommodates the uncertainties in undrilled or minimally drilled deposits that must be assessed using analogs. The publication is a collection of PowerPoint slides with accompanying comments.

  8. 21 CFR 114.90 - Methodology.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Methodology. 114.90 Section 114.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.90 Methodology. Methods that may be used to...

  9. 21 CFR 114.90 - Methodology.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Methodology. 114.90 Section 114.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.90 Methodology. Methods that may be used to...

  10. 21 CFR 114.90 - Methodology.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Methodology. 114.90 Section 114.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.90 Methodology. Methods that may be used to...

  11. Methodological Pluralism and Narrative Inquiry

    ERIC Educational Resources Information Center

    Michie, Michael

    2013-01-01

    This paper considers how the integral theory model of Nancy Davis and Laurie Callihan might be enacted using a different qualitative methodology, in this case the narrative methodology. The focus of narrative research is shown to be on "what meaning is being made" rather than "what is happening here" (quadrant 2 rather than…

  12. IMSF: Infinite Methodology Set Framework

    NASA Astrophysics Data System (ADS)

    Ota, Martin; Jelínek, Ivan

    Software development is usually an integration task in enterprise environment - few software applications work autonomously now. It is usually a collaboration of heterogeneous and unstable teams. One serious problem is lack of resources, a popular result being outsourcing, ‘body shopping’, and indirectly team and team member fluctuation. Outsourced sub-deliveries easily become black boxes with no clear development method used, which has a negative impact on supportability. Such environments then often face the problems of quality assurance and enterprise know-how management. The used methodology is one of the key factors. Each methodology was created as a generalization of a number of solved projects, and each methodology is thus more or less connected with a set of task types. When the task type is not suitable, it causes problems that usually result in an undocumented ad-hoc solution. This was the motivation behind formalizing a simple process for collaborative software engineering. Infinite Methodology Set Framework (IMSF) defines the ICT business process of adaptive use of methods for classified types of tasks. The article introduces IMSF and briefly comments its meta-model.

  13. 10 CFR 436.12 - Life cycle cost methodology.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Life cycle cost methodology. 436.12 Section 436.12 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.12 Life cycle cost methodology. The life cycle cost methodology...

  14. 10 CFR 436.12 - Life cycle cost methodology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Life cycle cost methodology. 436.12 Section 436.12 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.12 Life cycle cost methodology. The life cycle cost methodology...

  15. 10 CFR 436.12 - Life cycle cost methodology.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Life cycle cost methodology. 436.12 Section 436.12 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.12 Life cycle cost methodology. The life cycle cost methodology...

  16. 10 CFR 436.12 - Life cycle cost methodology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Life cycle cost methodology. 436.12 Section 436.12 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.12 Life cycle cost methodology. The life cycle cost methodology...

  17. 10 CFR 436.12 - Life cycle cost methodology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Life cycle cost methodology. 436.12 Section 436.12 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Methodology and Procedures for Life Cycle Cost Analyses § 436.12 Life cycle cost methodology. The life cycle cost methodology...

  18. Methodology for research I.

    PubMed

    Garg, Rakesh

    2016-09-01

    The conduct of research requires a systematic approach involving diligent planning and its execution as planned. It comprises various essential predefined components such as aims, population, conduct/technique, outcome and statistical considerations. These need to be objective, reliable and in a repeatable format. Hence, the understanding of the basic aspects of methodology is essential for any researcher. This is a narrative review and focuses on various aspects of the methodology for conduct of a clinical research. The relevant keywords were used for literature search from various databases and from bibliographies of the articles.

  19. Radioactive waste disposal fees-Methodology for calculation

    NASA Astrophysics Data System (ADS)

    Bemš, Július; Králík, Tomáš; Kubančák, Ján; Vašíček, Jiří; Starý, Oldřich

    2014-11-01

    This paper summarizes the methodological approach used for calculation of fee for low- and intermediate-level radioactive waste disposal and for spent fuel disposal. The methodology itself is based on simulation of cash flows related to the operation of system for waste disposal. The paper includes demonstration of methodology application on the conditions of the Czech Republic.

  20. The Electrochemistry of Organophosphorus Compounds.

    DTIC Science & Technology

    1988-01-20

    of hydrogen on the electrode surface. Mechanistkc views are further developed with the addition of water resulting in the formation of...the exclusive vlide product. Furthermore, carbonvl compounds were added to the electrolyses to react with the electrochemically-generated ylides via...the Wittig reaction. The resulting olefins were found to catalytically isomerize from the Z isomer to the E isomer upon reduction. The role of water

  1. Formation of Ketenimines via the Palladium-Catalyzed Decarboxylative π-Allylic Rearrangement of N-Alloc Ynamides.

    PubMed

    Alexander, Juliana R; Cook, Matthew J

    2017-11-03

    A new approach for the formation of ketenimines via a decarboxylative allylic rearrangement pathway that does not require strong stabilizing or protecting groups has been developed. The products can be readily hydrolyzed into their corresponding secondary amides or reacted with sulfur ylides to perform an additional [2,3]-Wittig process. Mechanistic studies suggest an outer-sphere process in which reductive alkylation is rate-limiting.

  2. General Methodology for Designing Spacecraft Trajectories

    NASA Technical Reports Server (NTRS)

    Condon, Gerald; Ocampo, Cesar; Mathur, Ravishankar; Morcos, Fady; Senent, Juan; Williams, Jacob; Davis, Elizabeth C.

    2012-01-01

    A methodology for designing spacecraft trajectories in any gravitational environment within the solar system has been developed. The methodology facilitates modeling and optimization for problems ranging from that of a single spacecraft orbiting a single celestial body to that of a mission involving multiple spacecraft and multiple propulsion systems operating in gravitational fields of multiple celestial bodies. The methodology consolidates almost all spacecraft trajectory design and optimization problems into a single conceptual framework requiring solution of either a system of nonlinear equations or a parameter-optimization problem with equality and/or inequality constraints.

  3. Technology transfer methodology

    NASA Technical Reports Server (NTRS)

    Labotz, Rich

    1991-01-01

    Information on technology transfer methodology is given in viewgraph form. Topics covered include problems in economics, technology drivers, inhibitors to using improved technology in development, technology application opportunities, and co-sponsorship of technology.

  4. A dual-catalysis approach to enantioselective [2 + 2] photocycloadditions using visible light.

    PubMed

    Du, Juana; Skubi, Kazimer L; Schultz, Danielle M; Yoon, Tehshik P

    2014-04-25

    In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here, we describe a strategy for eliminating the racemic background reaction in asymmetric [2 + 2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by using a dual-catalyst system consisting of a visible light-absorbing transition-metal photocatalyst and a stereocontrolling Lewis acid cocatalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions.

  5. A Dual-Catalysis Approach to Enantioselective [2+2] Photocycloadditions Using Visible Light

    PubMed Central

    Du, Juana; Skubi, Kazimer L.; Schultz, Danielle M.; Yoon, Tehshik P.

    2015-01-01

    In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here we describe a strategy for eliminating the racemic background reaction in asymmetric [2+2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by employing a dual-catalyst system consisting of a visible light-absorbing transition metal photocatalyst and a stereocontrolling Lewis acid co-catalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions. PMID:24763585

  6. Review of PCR methodology : executive summary.

    DOT National Transportation Integrated Search

    1998-01-01

    This study was conducted to review the Pavement Condition Rating (peR) : methodology currently used by the Ohio DOT. The results of the literature search in this : connection indicated that many Highway agencies use a similar methodology to rate thei...

  7. Software Requirements Engineering Methodology (Development)

    DTIC Science & Technology

    1979-06-01

    Higher Order Software [20]; and the Michael Jackson Design Methodology [21]. Although structured programming constructs have proven to be more useful...reviewed here. Similarly, the manual techniques for software design (e.g., HIPO Diagrams, Nassi-Schneidermann charts, Top-Down Design, the Michael ... Jackson Design Methodology, Yourdon’s Structured Design) are not addressed. 6.1.3 Research Programs There are a number of research programs underway

  8. Indications and Warning Methodology for Strategic Intelligence

    DTIC Science & Technology

    2017-12-01

    WARNING METHODOLOGY FOR STRATEGIC INTELLIGENCE by Susann Kimmelman December 2017 Thesis Co-Advisors: Robert Simeral James Wirtz THIS...Master’s thesis 4. TITLE AND SUBTITLE INDICATIONS AND WARNING METHODOLOGY FOR STRATEGIC INTELLIGENCE 5. FUNDING NUMBERS 6. AUTHOR(S) Susann...enterprise. The research found that, for homeland security, implementing a human-centric indications and warning methodology that focuses on the actor as

  9. Acoustic methodology review

    NASA Technical Reports Server (NTRS)

    Schlegel, R. G.

    1982-01-01

    It is important for industry and NASA to assess the status of acoustic design technology for predicting and controlling helicopter external noise in order for a meaningful research program to be formulated which will address this problem. The prediction methodologies available to the designer and the acoustic engineer are three-fold. First is what has been described as a first principle analysis. This analysis approach attempts to remove any empiricism from the analysis process and deals with a theoretical mechanism approach to predicting the noise. The second approach attempts to combine first principle methodology (when available) with empirical data to formulate source predictors which can be combined to predict vehicle levels. The third is an empirical analysis, which attempts to generalize measured trends into a vehicle noise prediction method. This paper will briefly address each.

  10. Assuring data transparency through design methodologies

    NASA Technical Reports Server (NTRS)

    Williams, Allen

    1990-01-01

    This paper addresses the role of design methodologies and practices in the assurance of technology transparency. The development of several subsystems on large, long life cycle government programs was analyzed to glean those characteristics in the design, development, test, and evaluation that precluded or enabled the insertion of new technology. The programs examined were Minuteman, DSP, B1-B, and space shuttle. All these were long life cycle, technology-intensive programs. The design methodologies (or lack thereof) and design practices for each were analyzed in terms of the success or failure in incorporating evolving technology. Common elements contributing to the success or failure were extracted and compared to current methodologies being proposed by the Department of Defense and NASA. The relevance of these practices to the design and deployment of Space Station Freedom were evaluated. In particular, appropriate methodologies now being used on the core development contract were examined.

  11. Direct functionalization processes: a journey from palladium to copper to iron to nickel to metal-free coupling reactions.

    PubMed

    Mousseau, James J; Charette, André B

    2013-02-19

    The possibility of finding novel disconnections for the efficient synthesis of organic molecules has driven the interest in developing technologies to directly functionalize C-H bonds. The ubiquity of these bonds makes such transformations attractive, while also posing several challenges. The first, and perhaps most important, is the selective functionalization of one C-H bond over another. Another key problem is inducing reactivity at sites that have been historically unreactive and difficult to access without prior inefficient prefunctionalization. Although remarkable advances have been made over the past decade toward solving these and other problems, several difficult tasks remain as researchers attempt to bring C-H functionalization reactions into common use. The functionalization of sp(3) centers continues to be challenging relative to their sp and sp(2) counterparts. Directing groups are often needed to increase the effective concentration of the catalyst at the targeted reaction site, forming thermodynamically stable coordination complexes. As such, the development of removable or convertible directing groups is desirable. Finally, the replacement of expensive rare earth reagents with less expensive and more sustainable catalysts or abandoning the use of catalysts entirely is essential for future practicality. This Account describes our efforts toward solving some of these quandaries. We began our work in this area with the direct arylation of N-iminopyridinium ylides as a universal means to derivatize the germane six-membered heterocycle. We found that the Lewis basic benzoyl group of the pyridinium ylide could direct a palladium catalyst toward insertion at the 2-position of the pyridinium ring, forming a thermodynamically stable six-membered metallocycle. Subsequently we discovered the arylation of the benzylic site of 2-picolonium ylides. The same N-benzoyl group could direct a number of inexpensive copper salts to the 2-position of the pyridinium ylide

  12. Extending the Instructional Systems Development Methodology.

    ERIC Educational Resources Information Center

    O'Neill, Colin E.

    1993-01-01

    Describes ways that components of Information Engineering (IE) methodology can be used by training system developers to extend Instructional Systems Development (ISD) methodology. Aspects of IE that are useful in ISD are described, including requirements determination, group facilitation, integrated automated tool support, and prototyping.…

  13. 10 CFR 766.102 - Calculation methodology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Calculation methodology. 766.102 Section 766.102 Energy DEPARTMENT OF ENERGY URANIUM ENRICHMENT DECONTAMINATION AND DECOMMISSIONING FUND; PROCEDURES FOR SPECIAL ASSESSMENT OF DOMESTIC UTILITIES Procedures for Special Assessment § 766.102 Calculation methodology. (a...

  14. 10 CFR 766.102 - Calculation methodology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Calculation methodology. 766.102 Section 766.102 Energy DEPARTMENT OF ENERGY URANIUM ENRICHMENT DECONTAMINATION AND DECOMMISSIONING FUND; PROCEDURES FOR SPECIAL ASSESSMENT OF DOMESTIC UTILITIES Procedures for Special Assessment § 766.102 Calculation methodology. (a...

  15. 10 CFR 766.102 - Calculation methodology.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Calculation methodology. 766.102 Section 766.102 Energy DEPARTMENT OF ENERGY URANIUM ENRICHMENT DECONTAMINATION AND DECOMMISSIONING FUND; PROCEDURES FOR SPECIAL ASSESSMENT OF DOMESTIC UTILITIES Procedures for Special Assessment § 766.102 Calculation methodology. (a...

  16. 10 CFR 766.102 - Calculation methodology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Calculation methodology. 766.102 Section 766.102 Energy DEPARTMENT OF ENERGY URANIUM ENRICHMENT DECONTAMINATION AND DECOMMISSIONING FUND; PROCEDURES FOR SPECIAL ASSESSMENT OF DOMESTIC UTILITIES Procedures for Special Assessment § 766.102 Calculation methodology. (a...

  17. New stereoselective intramolecular

    PubMed

    Alajarin; Vidal; Tovar; Ramirez De Arellano MC; Cossio; Arrieta; Lecea

    2000-11-03

    Efficient 1,4-asymmetric induction has been achieved in the highly stereocontrolled intramolecular [2 + 2] cycloadditions between ketenimines and imines, leading to 1,2-dihydroazeto[2, 1-b]quinazolines. The chiral methine carbon adjacent to the iminic nitrogen controls the exclusive formation of the cycloadducts with relative trans configuration at C2 and C8. The stepwise mechanistic model, based on theoretical calculations, fully supports the stereochemical outcome of these cycloadditions.

  18. Fluoride-Mediated Dephosphonylation of α-Diazo-β-carbonyl Phosphonates.

    PubMed

    Phatake, Ravindra S; Mullapudi, Venkannababu; Wakchaure, Vivek C; Ramana, Chepuri V

    2017-01-20

    The possibility of fluoride-mediated selective dephosphonylation of α-diazo-β-carbonyl phosphonates such as the Ohira-Bestmann reagent has been proposed and executed. The resulting α-diazocarbonyl intermediates undergo a (3 + 2)-cycloaddition at room temperature with conjugated olefins and benzynes. Interestingly, under the current conditions, the resulting cycloaddition products underwent either N-acylation (with excess α-diazo-β-carbonyl phosphonates) or Michael addition (with conjugated olefins).

  19. 24 CFR 904.205 - Training methodology.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Training methodology. 904.205... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homeownership Counseling and Training § 904.205 Training methodology. Equal in importance to the content of the pre- and post-occupancy training is the...

  20. 24 CFR 904.205 - Training methodology.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Training methodology. 904.205... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homeownership Counseling and Training § 904.205 Training methodology. Equal in importance to the content of the pre- and post-occupancy training is the...

  1. 24 CFR 904.205 - Training methodology.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Training methodology. 904.205... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homeownership Counseling and Training § 904.205 Training methodology. Equal in importance to the content of the pre- and post-occupancy training is the...

  2. 24 CFR 904.205 - Training methodology.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Training methodology. 904.205... DEVELOPMENT LOW RENT HOUSING HOMEOWNERSHIP OPPORTUNITIES Homeownership Counseling and Training § 904.205 Training methodology. Equal in importance to the content of the pre- and post-occupancy training is the...

  3. Decision-problem state analysis methodology

    NASA Technical Reports Server (NTRS)

    Dieterly, D. L.

    1980-01-01

    A methodology for analyzing a decision-problem state is presented. The methodology is based on the analysis of an incident in terms of the set of decision-problem conditions encountered. By decomposing the events that preceded an unwanted outcome, such as an accident, into the set of decision-problem conditions that were resolved, a more comprehensive understanding is possible. All human-error accidents are not caused by faulty decision-problem resolutions, but it appears to be one of the major areas of accidents cited in the literature. A three-phase methodology is presented which accommodates a wide spectrum of events. It allows for a systems content analysis of the available data to establish: (1) the resolutions made, (2) alternatives not considered, (3) resolutions missed, and (4) possible conditions not considered. The product is a map of the decision-problem conditions that were encountered as well as a projected, assumed set of conditions that should have been considered. The application of this methodology introduces a systematic approach to decomposing the events that transpired prior to the accident. The initial emphasis is on decision and problem resolution. The technique allows for a standardized method of accident into a scenario which may used for review or the development of a training simulation.

  4. The methodological defense of realism scrutinized.

    PubMed

    Wray, K Brad

    2015-12-01

    I revisit an older defense of scientific realism, the methodological defense, a defense developed by both Popper and Feyerabend. The methodological defense of realism concerns the attitude of scientists, not philosophers of science. The methodological defense is as follows: a commitment to realism leads scientists to pursue the truth, which in turn is apt to put them in a better position to get at the truth. In contrast, anti-realists lack the tenacity required to develop a theory to its fullest. As a consequence, they are less likely to get at the truth. My aim is to show that the methodological defense is flawed. I argue that a commitment to realism does not always benefit science, and that there is reason to believe that a research community with both realists and anti-realists in it may be better suited to advancing science. A case study of the Copernican Revolution in astronomy supports this claim. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Methodological convergence of program evaluation designs.

    PubMed

    Chacón-Moscoso, Salvador; Anguera, M Teresa; Sanduvete-Chaves, Susana; Sánchez-Martín, Milagrosa

    2014-01-01

    Nowadays, the confronting dichotomous view between experimental/quasi-experimental and non-experimental/ethnographic studies still exists but, despite the extensive use of non-experimental/ethnographic studies, the most systematic work on methodological quality has been developed based on experimental and quasi-experimental studies. This hinders evaluators and planners' practice of empirical program evaluation, a sphere in which the distinction between types of study is changing continually and is less clear. Based on the classical validity framework of experimental/quasi-experimental studies, we carry out a review of the literature in order to analyze the convergence of design elements in methodological quality in primary studies in systematic reviews and ethnographic research. We specify the relevant design elements that should be taken into account in order to improve validity and generalization in program evaluation practice in different methodologies from a practical methodological and complementary view. We recommend ways to improve design elements so as to enhance validity and generalization in program evaluation practice.

  6. Systematic Review Methodology in Higher Education

    ERIC Educational Resources Information Center

    Bearman, Margaret; Smith, Calvin D.; Carbone, Angela; Slade, Susan; Baik, Chi; Hughes-Warrington, Marnie; Neumann, David L.

    2012-01-01

    Systematic review methodology can be distinguished from narrative reviews of the literature through its emphasis on transparent, structured and comprehensive approaches to searching the literature and its requirement for formal synthesis of research findings. There appears to be relatively little use of the systematic review methodology within the…

  7. 42 CFR 433.206 - Threshold methodology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Threshold methodology. 433.206 Section 433.206 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE FISCAL ADMINISTRATION Methodologies for Determining Federal Share of Medicaid Expenditures for Adult Eligibilit...

  8. 42 CFR 433.206 - Threshold methodology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Threshold methodology. 433.206 Section 433.206 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS STATE FISCAL ADMINISTRATION Methodologies for Determining Federal Share of Medicaid Expenditures for Adult Eligibilit...

  9. The Speaker Respoken: Material Rhetoric as Feminist Methodology.

    ERIC Educational Resources Information Center

    Collins, Vicki Tolar

    1999-01-01

    Presents a methodology based on the concept of "material rhetoric" that can help scholars avoid problems as they reclaim women's historical texts. Defines material rhetoric and positions it theoretically in relation to other methodologies, including bibliographical studies, reception theory, and established feminist methodologies. Illustrates…

  10. Peptide-Appended Permethylated β-Cyclodextrins with Hydrophilic and Hydrophobic Spacers

    PubMed Central

    2017-01-01

    A novel synthetic methodology, employing a combination of the strain-promoted azide–alkyne cycloaddition and maleimide–thiol reactions, for the preparation of permethylated β-cyclodextrin-linker-peptidyl conjugates is reported. Two different bifunctional maleimide cross-linking probes, the polyethylene glycol containing hydrophilic linker bicyclo[6.1.0] nonyne-maleimide and the hydrophobic 5′-dibenzoazacyclooctyne-maleimide, were attached to azide-appended permethylated β-cyclodextrin. The successfully introduced maleimide function was exploited to covalently graft a cysteine-containing peptide (Ac-Tyr-Arg-Cys-Amide) to produce the target conjugates. The final target compounds were isolated in high purity after purification by isocratic preparative reverse-phase high-performance liquid chromatography. This novel synthetic approach is expected to give access to many different cyclodextrin–linker peptides. PMID:28697600

  11. Methodologies for Crawler Based Web Surveys.

    ERIC Educational Resources Information Center

    Thelwall, Mike

    2002-01-01

    Describes Web survey methodologies used to study the content of the Web, and discusses search engines and the concept of crawling the Web. Highlights include Web page selection methodologies; obstacles to reliable automatic indexing of Web sites; publicly indexable pages; crawling parameters; and tests for file duplication. (Contains 62…

  12. Embodied Writing: Choreographic Composition as Methodology

    ERIC Educational Resources Information Center

    Ulmer, Jasmine B.

    2015-01-01

    This paper seeks to examine how embodied methodological approaches might inform dance education practice and research. Through a series of examples, this paper explores how choreographic writing might function as an embodied writing methodology. Here, choreographic writing is envisioned as a form of visual word choreography in which words move,…

  13. Solid Waste Management Planning--A Methodology

    ERIC Educational Resources Information Center

    Theisen, Hilary M.; And Others

    1975-01-01

    This article presents a twofold solid waste management plan consisting of a basic design methodology and a decision-making methodology. The former provides a framework for the developing plan while the latter builds flexibility into the design so that there is a model for use during the planning process. (MA)

  14. Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

    PubMed Central

    Mazurkiewicz, Roman; Fryczkowska, Beata

    2017-01-01

    The main synthetic routes towards vinylphosphonium salts and their wide applications in organic synthesis are discussed in this review. Particular attention is paid to the use of these compounds as building blocks for the synthesis of carbo- and heterocyclic systems after their prior transformation into the corresponding phosphorus ylides, followed by the intramolecular Wittig reaction with various types of nucleophiles containing a carbonyl function in their structures. PMID:29564008

  15. Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy.

    PubMed

    Wei, Hongbo; Li, Yun; Xiao, Ke; Cheng, Bin; Wang, Huifei; Hu, Lin; Zhai, Hongbin

    2015-12-18

    An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.

  16. 2-Hydroxybenzophenone as a Chemical Auxiliary for the Activation of Ketiminoesters for Highly Enantioselective Addition to Nitroalkenes under Bifunctional Catalysis.

    PubMed

    Guerrero-Corella, Andrea; Esteban, Francisco; Iniesta, Manuel; Martín-Somer, Ana; Parra, Mario; Díaz-Tendero, Sergio; Fraile, Alberto; Alemán, Jose

    2018-05-04

    An organocatalytic system is presented for the Michael addition of monoactivated glycine ketimine ylides with a bifunctional catalyst. The ketimine bears an ortho hydroxy group, which increases the acidity of the methylene hydrogen atoms and enhances the reactivity, thus allowing the synthesis of a large variety of α,γ-diamino acid derivatives with excellent stereoselectivity. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  17. 18 CFR 342.4 - Other rate changing methodologies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Other rate changing methodologies. 342.4 Section 342.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... METHODOLOGIES AND PROCEDURES § 342.4 Other rate changing methodologies. (a) Cost-of-service rates. A carrier may...

  18. Using Modern Methodologies with Maintenance Software

    NASA Technical Reports Server (NTRS)

    Streiffert, Barbara A.; Francis, Laurie K.; Smith, Benjamin D.

    2014-01-01

    Jet Propulsion Laboratory uses multi-mission software produced by the Mission Planning and Sequencing (MPS) team to process, simulate, translate, and package the commands that are sent to a spacecraft. MPS works under the auspices of the Multi-Mission Ground Systems and Services (MGSS). This software consists of nineteen applications that are in maintenance. The MPS software is classified as either class B (mission critical) or class C (mission important). The scheduling of tasks is difficult because mission needs must be addressed prior to performing any other tasks and those needs often spring up unexpectedly. Keeping track of the tasks that everyone is working on is also difficult because each person is working on a different software component. Recently the group adopted the Scrum methodology for planning and scheduling tasks. Scrum is one of the newer methodologies typically used in agile development. In the Scrum development environment, teams pick their tasks that are to be completed within a sprint based on priority. The team specifies the sprint length usually a month or less. Scrum is typically used for new development of one application. In the Scrum methodology there is a scrum master who is a facilitator who tries to make sure that everything moves smoothly, a product owner who represents the user(s) of the software and the team. MPS is not the traditional environment for the Scrum methodology. MPS has many software applications in maintenance, team members who are working on disparate applications, many users, and is interruptible based on mission needs, issues and requirements. In order to use scrum, the methodology needed adaptation to MPS. Scrum was chosen because it is adaptable. This paper is about the development of the process for using scrum, a new development methodology, with a team that works on disparate interruptible tasks on multiple software applications.

  19. On the methodology of Engineering Geodesy

    NASA Astrophysics Data System (ADS)

    Brunner, Fritz K.

    2007-09-01

    Textbooks on geodetic surveying usually describe a very small number of principles which should provide the foundation of geodetic surveying. Here, the author argues that an applied field, such as engineering geodesy, has a methodology as foundation rather than a few principles. Ten methodological elements (ME) are identified: (1) Point discretisation of natural surfaces and objects, (2) distinction between coordinate and observation domain, (3) definition of reference systems, (4) specification of unknown parameters and desired precisions, (5) geodetic network and observation design, (6) quality control of equipment, (7) quality control of measurements, (8) establishment of measurement models, (9) establishment of parameter estimation models, (10) quality control of results. Each ME consists of a suite of theoretical developments, geodetic techniques and calculation procedures, which will be discussed. This paper is to be considered a first attempt at identifying the specific elements of the methodology of engineering geodesy. A better understanding of this methodology could lead to an increased objectivity, to a transformation of subjective practical experiences into objective working methods, and consequently to a new structure for teaching this rather diverse subject.

  20. [Qualitative research methodology in health care].

    PubMed

    Bedregal, Paula; Besoain, Carolina; Reinoso, Alejandro; Zubarew, Tamara

    2017-03-01

    Health care research requires different methodological approaches such as qualitative and quantitative analyzes to understand the phenomena under study. Qualitative research is usually the least considered. Central elements of the qualitative method are that the object of study is constituted by perceptions, emotions and beliefs, non-random sampling by purpose, circular process of knowledge construction, and methodological rigor throughout the research process, from quality design to the consistency of results. The objective of this work is to contribute to the methodological knowledge about qualitative research in health services, based on the implementation of the study, “The transition process from pediatric to adult services: perspectives from adolescents with chronic diseases, caregivers and health professionals”. The information gathered through the qualitative methodology facilitated the understanding of critical points, barriers and facilitators of the transition process of adolescents with chronic diseases, considering the perspective of users and the health team. This study allowed the design of a transition services model from pediatric to adult health services based on the needs of adolescents with chronic diseases, their caregivers and the health team.

  1. A methodology for hypersonic transport technology planning

    NASA Technical Reports Server (NTRS)

    Repic, E. M.; Olson, G. A.; Milliken, R. J.

    1973-01-01

    A systematic procedure by which the relative economic value of technology factors affecting design, configuration, and operation of a hypersonic cruise transport can be evaluated is discussed. Use of the methodology results in identification of first-order economic gains potentially achievable by projected advances in each of the definable, hypersonic technologies. Starting with a baseline vehicle, the formulas, procedures and forms which are integral parts of this methodology are developed. A demonstration of the methodology is presented for one specific hypersonic vehicle system.

  2. Development of Methodology for Programming Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Erol, Kutluhan; Levy, Renato; Lang, Lun

    2004-01-01

    A brief report discusses the rationale for, and the development of, a methodology for generating computer code for autonomous-agent-based systems. The methodology is characterized as enabling an increase in the reusability of the generated code among and within such systems, thereby making it possible to reduce the time and cost of development of the systems. The methodology is also characterized as enabling reduction of the incidence of those software errors that are attributable to the human failure to anticipate distributed behaviors caused by the software. A major conceptual problem said to be addressed in the development of the methodology was that of how to efficiently describe the interfaces between several layers of agent composition by use of a language that is both familiar to engineers and descriptive enough to describe such interfaces unambivalently

  3. Expert System Development Methodology (ESDM)

    NASA Technical Reports Server (NTRS)

    Sary, Charisse; Gilstrap, Lewey; Hull, Larry G.

    1990-01-01

    The Expert System Development Methodology (ESDM) provides an approach to developing expert system software. Because of the uncertainty associated with this process, an element of risk is involved. ESDM is designed to address the issue of risk and to acquire the information needed for this purpose in an evolutionary manner. ESDM presents a life cycle in which a prototype evolves through five stages of development. Each stage consists of five steps, leading to a prototype for that stage. Development may proceed to a conventional development methodology (CDM) at any time if enough has been learned about the problem to write requirements. ESDM produces requirements so that a product may be built with a CDM. ESDM is considered preliminary because is has not yet been applied to actual projects. It has been retrospectively evaluated by comparing the methods used in two ongoing expert system development projects that did not explicitly choose to use this methodology but which provided useful insights into actual expert system development practices and problems.

  4. Air traffic control system baseline methodology guide.

    DOT National Transportation Integrated Search

    1999-06-01

    The Air Traffic Control System Baseline Methodology Guide serves as a reference in the design and conduct of baseline studies. : Engineering research psychologists are the intended audience for the Methodology Guide, which focuses primarily on techni...

  5. 10 CFR 455.64 - Life-cycle cost methodology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Life-cycle cost methodology. 455.64 Section 455.64 Energy..., Hospitals, Units of Local Government, and Public Care Institutions § 455.64 Life-cycle cost methodology. (a) The life-cycle cost methodology under § 455.63(b) of this part is a systematic comparison of the...

  6. 10 CFR 455.64 - Life-cycle cost methodology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Life-cycle cost methodology. 455.64 Section 455.64 Energy..., Hospitals, Units of Local Government, and Public Care Institutions § 455.64 Life-cycle cost methodology. (a) The life-cycle cost methodology under § 455.63(b) of this part is a systematic comparison of the...

  7. Soft Systems Methodology

    NASA Astrophysics Data System (ADS)

    Checkland, Peter; Poulter, John

    Soft systems methodology (SSM) is an approach for tackling problematical, messy situations of all kinds. It is an action-oriented process of inquiry into problematic situations in which users learn their way from finding out about the situation, to taking action to improve it. The learning emerges via an organised process in which the situation is explored using a set of models of purposeful action (each built to encapsulate a single worldview) as intellectual devices, or tools, to inform and structure discussion about a situation and how it might be improved. This paper, written by the original developer Peter Checkland and practitioner John Poulter, gives a clear and concise account of the approach that covers SSM's specific techniques, the learning cycle process of the methodology and the craft skills which practitioners develop. This concise but theoretically robust account nevertheless includes the fundamental concepts, techniques, core tenets described through a wide range of settings.

  8. Hardware proofs using EHDM and the RSRE verification methodology

    NASA Technical Reports Server (NTRS)

    Butler, Ricky W.; Sjogren, Jon A.

    1988-01-01

    Examined is a methodology for hardware verification developed by Royal Signals and Radar Establishment (RSRE) in the context of the SRI International's Enhanced Hierarchical Design Methodology (EHDM) specification/verification system. The methodology utilizes a four-level specification hierarchy with the following levels: functional level, finite automata model, block model, and circuit level. The properties of a level are proved as theorems in the level below it. This methodology is applied to a 6-bit counter problem and is critically examined. The specifications are written in EHDM's specification language, Extended Special, and the proofs are improving both the RSRE methodology and the EHDM system.

  9. Reviewing the methodology of an integrative review.

    PubMed

    Hopia, Hanna; Latvala, Eila; Liimatainen, Leena

    2016-12-01

    Whittemore and Knafl's updated description of methodological approach for integrative review was published in 2005. Since then, the five stages of the approach have been regularly used as a basic conceptual structure of the integrative reviews conducted by nursing researchers. However, this methodological approach is seldom examined from the perspective of how systematically and rigorously the stages are implemented in the published integrative reviews. To appraise the selected integrative reviews on the basis of the methodological approach according to the five stages published by Whittemore and Knafl in 2005. A literature review was used in this study. CINAHL (Cumulative Index to Nursing and Allied Health), PubMed, OVID (Journals@Ovid) and the Cochrane Library databases were searched for integrative reviews published between 2002 and 2014. Papers were included if they used the methodological approach described by Whittemore and Knafl, were published in English and were focused on nursing education or nursing expertise. A total of 259 integrative review publications for potential inclusion were identified. Ten integrative reviews fulfilled the inclusion criteria. Findings from the studies were extracted and critically examined according to the five methodological stages. The reviews assessed followed the guidelines of the stated methodology approach to different extents. The stages of literature search, data evaluation and data analysis were fairly poorly formulated and only partially implemented in the studies included in the sample. The other two stages, problem identification and presentation, followed those described in the methodological approach quite well. Increasing use of research in clinical practice is inevitable, and therefore, integrative reviews can play a greater role in developing evidence-based nursing practices. Because of this, nurse researchers should pay more attention to sound integrative nursing research to systematise the review process and

  10. Methodological triangulation: an approach to understanding data.

    PubMed

    Bekhet, Abir K; Zauszniewski, Jaclene A

    2012-01-01

    To describe the use of methodological triangulation in a study of how people who had moved to retirement communities were adjusting. Methodological triangulation involves using more than one kind of method to study a phenomenon. It has been found to be beneficial in providing confirmation of findings, more comprehensive data, increased validity and enhanced understanding of studied phenomena. While many researchers have used this well-established technique, there are few published examples of its use. The authors used methodological triangulation in their study of people who had moved to retirement communities in Ohio, US. A blended qualitative and quantitative approach was used. The collected qualitative data complemented and clarified the quantitative findings by helping to identify common themes. Qualitative data also helped in understanding interventions for promoting 'pulling' factors and for overcoming 'pushing' factors of participants. The authors used focused research questions to reflect the research's purpose and four evaluative criteria--'truth value', 'applicability', 'consistency' and 'neutrality'--to ensure rigour. This paper provides an example of how methodological triangulation can be used in nursing research. It identifies challenges associated with methodological triangulation, recommends strategies for overcoming them, provides a rationale for using triangulation and explains how to maintain rigour. Methodological triangulation can be used to enhance the analysis and the interpretation of findings. As data are drawn from multiple sources, it broadens the researcher's insight into the different issues underlying the phenomena being studied.

  11. Methods for the synthesis of donor-acceptor cyclopropanes

    NASA Astrophysics Data System (ADS)

    Tomilov, Yu V.; Menchikov, L. G.; Novikov, R. A.; Ivanova, O. A.; Trushkov, I. V.

    2018-03-01

    The interest in cyclopropane derivatives is caused by the facts that, first, the three-carbon ring is present in quite a few natural and biologically active compounds and, second, compounds with this ring are convenient building blocks for the synthesis of diverse molecules (acyclic, alicyclic and heterocyclic). The carbon–carbon bonds in cyclopropane are kinetically rather inert; hence, they need to be activated to be involved in reactions. An efficient way of activation is to introduce vicinal electron-donating and electron-withdrawing substituents into the ring; these substrates are usually referred to as donor-acceptor cyclopropanes. This review gives a systematic account of the key methods for the synthesis of donor-acceptor cyclopropanes. The most important among them are reactions of nucleophilic alkenes with diazo compounds and iodonium ylides and approaches based on reactions of electrophilic alkenes with sulfur ylides (the Corey–Chaykovsky reaction). Among other methods used for this purpose, noteworthy are cycloalkylation of CH-acids, addition of α-halocarbonyl compounds to alkenes, cyclization via 1,3-elimination, reactions of alkenes with halocarbenes followed by reduction, the Simmons–Smith reaction and some other. The scope of applicability and prospects of various methods for the synthesis of donor-acceptor cyclopropanes are discussed. The bibliography includes 530 references.

  12. A dynamic systems engineering methodology research study. Phase 2: Evaluating methodologies, tools, and techniques for applicability to NASA's systems projects

    NASA Technical Reports Server (NTRS)

    Paul, Arthur S.; Gill, Tepper L.; Maclin, Arlene P.

    1989-01-01

    A study of NASA's Systems Management Policy (SMP) concluded that the primary methodology being used by the Mission Operations and Data Systems Directorate and its subordinate, the Networks Division, is very effective. Still some unmet needs were identified. This study involved evaluating methodologies, tools, and techniques with the potential for resolving the previously identified deficiencies. Six preselected methodologies being used by other organizations with similar development problems were studied. The study revealed a wide range of significant differences in structure. Each system had some strengths but none will satisfy all of the needs of the Networks Division. Areas for improvement of the methodology being used by the Networks Division are listed with recommendations for specific action.

  13. Regiochemically controlled synthesis of a β-4-β' [70]fullerene bis-adduct

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cerón, Maira R.; Castro, Edison; Neti, Venkata S. Pavan K.

    2016-12-22

    A β-4-β' C 70 bis-adduct regioisomer and an uncommon mono-adduct β-malonate C 70 derivative were synthesized by using a Diels–Alder cycloaddition followed by an addition–elimination of bromo-ethylmalonate and a retro-Diels–Alder cycloaddition reaction. Here, we also report the regioselective synthesis and spectroscopic characterization of C s-symmetric tris- and C 2v-symmetric tetra-adducts of C 70, which are the precursors of the mono- and bis-adduct final products.

  14. Concurrent Stabilization and Imaging of a Novel Polymer for Second Harmonic Generation via In Situ Photopolymerization

    DTIC Science & Technology

    1994-04-26

    polymers bearing acrylatel 5. 16 ) or ethyny117 ) groups. Alternately, photoinduced crosslinking via a [2+2]cycloaddition of cinnamates , 18-21) a photo...groups.8 .9 Alternately, some improvement of stability has been achieved through photo-induced crosslinking via either a [2+2]cycloaddition of cinnamates ...2.5 x 2.5 cm) were dipped halfway into hydroiodic acid (55 % in water; 50 °C), for 30s to remove the ITO coating, polished with 0.5 g~m aluminum

  15. Rh(III)-Catalyzed C-H Activation of Benzoylacetonitriles and Tandem Cyclization with Diazo Compounds to Substituted Benzo[ de]chromenes.

    PubMed

    Fang, Feifei; Zhang, Chunmei; Zhou, Chaofan; Li, Yazhou; Zhou, Yu; Liu, Hong

    2018-04-06

    Rh (III)-catalyzed C-H activation of benzoylacetonitriles in coupling with diazo compounds was developed to synthesize diversified substituted benzo[ de]chromenes via a formal (4 + 2) cycloaddition with a diazo compound and subsequent tandem (4 + 2) cycloaddition with another diazo compound. Intriguingly, synthesis of substituted benzo[ de]chromenes and their decarboxylation products could be realized by controlling the reaction conditions. These reactions have a broad range of substrates, moderate to good yields, and high regioselectivity.

  16. Methodological Issues and Practices in Qualitative Research.

    ERIC Educational Resources Information Center

    Bradley, Jana

    1993-01-01

    Discusses methodological issues concerning qualitative research and describes research practices that qualitative researchers use to address these methodological issues. Topics discussed include the researcher as interpreter, the emergent nature of qualitative research, understanding the experience of others, trustworthiness in qualitative…

  17. Second-Generation Difluorinated Cyclooctynes for Copper-Free Click Chemistry

    PubMed Central

    2008-01-01

    The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed “click chemistry”, is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the need for copper catalysis. Here we report a novel class of DIFO reagents for copper-free click chemistry that are considerably more synthetically tractable. The new analogues maintained the same elevated rates of [3 + 2] cycloaddition as the parent compound and were used for imaging glycans on live cells. These second-generation DIFO reagents should expand the use of copper-free click chemistry in the hands of biologists. PMID:18680289

  18. Second-generation difluorinated cyclooctynes for copper-free click chemistry.

    PubMed

    Codelli, Julian A; Baskin, Jeremy M; Agard, Nicholas J; Bertozzi, Carolyn R

    2008-08-27

    The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed "click chemistry", is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the need for copper catalysis. Here we report a novel class of DIFO reagents for copper-free click chemistry that are considerably more synthetically tractable. The new analogues maintained the same elevated rates of [3 + 2] cycloaddition as the parent compound and were used for imaging glycans on live cells. These second-generation DIFO reagents should expand the use of copper-free click chemistry in the hands of biologists.

  19. Agile methodology selection criteria: IT start-up case study

    NASA Astrophysics Data System (ADS)

    Micic, Lj

    2017-05-01

    Project management in modern IT companies is often based on agile methodologies which have several advantages compared to traditional methodologies such is waterfall. Having in mind that clients sometimes change project during development it is crucial for an IT company to choose carefully which methodology is going to implement and is it going to be mostly based on one or is it going got be combination of several. There are several modern and often used methodologies but among those Scrum, Kanban and XP programming are usually the most common. Sometimes companies use mostly tools and procedures from one but quite often they use some of the combination of those methodologies. Having in mind that those methodologies are just a framework they allow companies to adapt it for their specific projects as well as for other limitations. These methodologies are in limited usage Bosnia but more and more IT companies are starting to use agile methodologies because it is practice and common not just for their clients abroad but also starting to be the only option in order to deliver quality product on time. However it is always challenging which methodology or combination of several companies should implement and how to connect it to its own project, organizational framework and HR management. This paper presents one case study based on local IT start up and delivers solution based on theoretical framework and practical limitations that case company has.

  20. Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

    PubMed

    Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

    2017-01-01

    Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.

  1. Experimental Methodology for Measuring Combustion and Injection-Coupled Responses

    NASA Technical Reports Server (NTRS)

    Cavitt, Ryan C.; Frederick, Robert A.; Bazarov, Vladimir G.

    2006-01-01

    A Russian scaling methodology for liquid rocket engines utilizing a single, full scale element is reviewed. The scaling methodology exploits the supercritical phase of the full scale propellants to simplify scaling requirements. Many assumptions are utilized in the derivation of the scaling criteria. A test apparatus design is presented to implement the Russian methodology and consequently verify the assumptions. This test apparatus will allow researchers to assess the usefulness of the scaling procedures and possibly enhance the methodology. A matrix of the apparatus capabilities for a RD-170 injector is also presented. Several methods to enhance the methodology have been generated through the design process.

  2. Comparison between two methodologies for urban drainage decision aid.

    PubMed

    Moura, P M; Baptista, M B; Barraud, S

    2006-01-01

    The objective of the present work is to compare two methodologies based on multicriteria analysis for the evaluation of stormwater systems. The first methodology was developed in Brazil and is based on performance-cost analysis, the second one is ELECTRE III. Both methodologies were applied to a case study. Sensitivity and robustness analyses were then carried out. These analyses demonstrate that both methodologies have equivalent results, and present low sensitivity and high robustness. These results prove that the Brazilian methodology is consistent and can be used safely in order to select a good solution or a small set of good solutions that could be compared with more detailed methods afterwards.

  3. Total System Design (TSD) Methodology Assessment.

    DTIC Science & Technology

    1983-01-01

    hardware implementation. Author: Martin - Marietta Aerospace Title: Total System Design Methodology Source: Martin - Marietta Technical Report MCR -79-646...systematic, rational approach to computer systems design is needed. Martin - Marietta has produced a Total System Design Methodology to support such design...gathering and ordering. The purpose of the paper is to document the existing TSD methoeology at Martin - Marietta , describe the supporting tools, and

  4. Representation of scientific methodology in secondary science textbooks

    NASA Astrophysics Data System (ADS)

    Binns, Ian C.

    The purpose of this investigation was to assess the representation of scientific methodology in secondary science textbooks. More specifically, this study looked at how textbooks introduced scientific methodology and to what degree the examples from the rest of the textbook, the investigations, and the images were consistent with the text's description of scientific methodology, if at all. The sample included eight secondary science textbooks from two publishers, McGraw-Hill/Glencoe and Harcourt/Holt, Rinehart & Winston. Data consisted of all student text and teacher text that referred to scientific methodology. Second, all investigations in the textbooks were analyzed. Finally, any images that depicted scientists working were also collected and analyzed. The text analysis and activity analysis used the ethnographic content analysis approach developed by Altheide (1996). The rubrics used for the text analysis and activity analysis were initially guided by the Benchmarks (AAAS, 1993), the NSES (NRC, 1996), and the nature of science literature. Preliminary analyses helped to refine each of the rubrics and grounded them in the data. Image analysis used stereotypes identified in the DAST literature. Findings indicated that all eight textbooks presented mixed views of scientific methodology in their initial descriptions. Five textbooks placed more emphasis on the traditional view and three placed more emphasis on the broad view. Results also revealed that the initial descriptions, examples, investigations, and images all emphasized the broad view for Glencoe Biology and the traditional view for Chemistry: Matter and Change. The initial descriptions, examples, investigations, and images in the other six textbooks were not consistent. Overall, the textbook with the most appropriate depiction of scientific methodology was Glencoe Biology and the textbook with the least appropriate depiction of scientific methodology was Physics: Principles and Problems. These findings

  5. Novel optoelectronic methodology for testing of MOEMS

    NASA Astrophysics Data System (ADS)

    Pryputniewicz, Ryszard J.; Furlong, Cosme

    2003-01-01

    Continued demands for delivery of high performance micro-optoelectromechanical systems (MOEMS) place unprecedented requirements on methods used in their development and operation. Metrology is a major and inseparable part of these methods. Optoelectronic methodology is an essential field of metrology. Due to its scalability, optoelectronic methodology is particularly suitable for testing of MOEMS where measurements must be made with ever increasing accuracy and precision. This was particularly evident during the last few years, characterized by miniaturization of devices, when requirements for measurements have rapidly increased as the emerging technologies introduced new products, especially, optical MEMS. In this paper, a novel optoelectronic methodology for testing of MOEMS is described and its applications are illustrated with representative examples. These examples demonstrate capability to measure submicron deformations of various components of the micromirror device, under operating conditions, and show viability of the optoelectronic methodology for testing of MOEMS.

  6. Human-Computer System Development Methodology for the Dialogue Management System.

    DTIC Science & Technology

    1982-05-01

    methodologies [HOSIJ78] are given below: I. The Michael Jackson Methodology [JACKM75] 2. The Warnier-Orr Methodolgy [HOSIJ78] 3. SADT (Structured...All the mentioned methodologies use top-down development strategy. The first two methodologies above ( Michael Jackson and Warnier-Orr) use data as the

  7. Using Q Methodology in Quality Improvement Projects.

    PubMed

    Tiernon, Paige; Hensel, Desiree; Roy-Ehri, Leah

    Q methodology consists of a philosophical framework and procedures to identify subjective viewpoints that may not be well understood, but its use in nursing is still quite limited. We describe how Q methodology can be used in quality improvement projects to better understand local viewpoints that act as facilitators or barriers to the implementation of evidence-based practice. We describe the use of Q methodology to identify nurses' attitudes about the provision of skin-to-skin care after cesarean birth. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  8. A design and implementation methodology for diagnostic systems

    NASA Technical Reports Server (NTRS)

    Williams, Linda J. F.

    1988-01-01

    A methodology for design and implementation of diagnostic systems is presented. Also discussed are the advantages of embedding a diagnostic system in a host system environment. The methodology utilizes an architecture for diagnostic system development that is hierarchical and makes use of object-oriented representation techniques. Additionally, qualitative models are used to describe the host system components and their behavior. The methodology architecture includes a diagnostic engine that utilizes a combination of heuristic knowledge to control the sequence of diagnostic reasoning. The methodology provides an integrated approach to development of diagnostic system requirements that is more rigorous than standard systems engineering techniques. The advantages of using this methodology during various life cycle phases of the host systems (e.g., National Aerospace Plane (NASP)) include: the capability to analyze diagnostic instrumentation requirements during the host system design phase, a ready software architecture for implementation of diagnostics in the host system, and the opportunity to analyze instrumentation for failure coverage in safety critical host system operations.

  9. Methodological Limitations of the Application of Expert Systems Methodology in Reading.

    ERIC Educational Resources Information Center

    Willson, Victor L.

    Methodological deficiencies inherent in expert-novice reading research make it impossible to draw inferences about curriculum change. First, comparisons of intact groups are often used as a basis for making causal inferences about how observed characteristics affect behaviors. While comparing different groups is not by itself a useless activity,…

  10. Summarizing Monte Carlo Results in Methodological Research.

    ERIC Educational Resources Information Center

    Harwell, Michael R.

    Monte Carlo studies of statistical tests are prominently featured in the methodological research literature. Unfortunately, the information from these studies does not appear to have significantly influenced methodological practice in educational and psychological research. One reason is that Monte Carlo studies lack an overarching theory to guide…

  11. Grounded Theory Methodology: Positivism, Hermeneutics, and Pragmatism

    ERIC Educational Resources Information Center

    Age, Lars-Johan

    2011-01-01

    Glaserian grounded theory methodology, which has been widely adopted as a scientific methodology in recent decades, has been variously characterised as "hermeneutic" and "positivist." This commentary therefore takes a different approach to characterising grounded theory by undertaking a comprehensive analysis of: (a) the philosophical paradigms of…

  12. A Narrative in Search of a Methodology.

    PubMed

    Treloar, Anna; Stone, Teresa Elizabeth; McMillan, Margaret; Flakus, Kirstin

    2015-07-01

    Research papers present us with the summaries of scholars' work; what we readers do not see are the struggles behind the decision to choose one methodology over another. A student's mental health portfolio contained a narrative that led to an exploration of the most appropriate methodology for a projected study of clinical anecdotes told by nurses who work in mental health settings to undergraduates and new recruits about mental health nursing. This paper describes the process of struggle, beginning with the student's account, before posing a number of questions needing answers before the choice of the most appropriate methodology. We argue, after discussing the case for the use of literary analysis, discourse analysis, symbolic interactionism, hermeneutics, and narrative research, that case study research is the methodology of choice. Case study is frequently used in educational research and is sufficiently flexible to allow for an exploration of the phenomenon. © 2014 Wiley Periodicals, Inc.

  13. Architectural Methodology Report

    NASA Technical Reports Server (NTRS)

    Dhas, Chris

    2000-01-01

    The establishment of conventions between two communicating entities in the end systems is essential for communications. Examples of the kind of decisions that need to be made in establishing a protocol convention include the nature of the data representation, the for-mat and the speed of the date representation over the communications path, and the sequence of control messages (if any) which are sent. One of the main functions of a protocol is to establish a standard path between the communicating entities. This is necessary to create a virtual communications medium with certain desirable characteristics. In essence, it is the function of the protocol to transform the characteristics of the physical communications environment into a more useful virtual communications model. The final function of a protocol is to establish standard data elements for communications over the path; that is, the protocol serves to create a virtual data element for exchange. Other systems may be constructed in which the transferred element is a program or a job. Finally, there are special purpose applications in which the element to be transferred may be a complex structure such as all or part of a graphic display. NASA's Glenn Research Center (GRC) defines and develops advanced technology for high priority national needs in communications technologies for application to aeronautics and space. GRC tasked Computer Networks and Software Inc. (CNS) to describe the methodologies used in developing a protocol architecture for an in-space Internet node. The node would support NASA:s four mission areas: Earth Science; Space Science; Human Exploration and Development of Space (HEDS); Aerospace Technology. This report presents the methodology for developing the protocol architecture. The methodology addresses the architecture for a computer communications environment. It does not address an analog voice architecture.

  14. Complicating Methodological Transparency

    ERIC Educational Resources Information Center

    Bridges-Rhoads, Sarah; Van Cleave, Jessica; Hughes, Hilary E.

    2016-01-01

    A historical indicator of the quality, validity, and rigor of qualitative research has been the documentation and disclosure of the behind-the-scenes work of the researcher. In this paper, we use what we call "methodological data" as a tool to complicate the possibility and desirability of such transparency. Specifically, we draw on our…

  15. VIII. THE PAST, PRESENT, AND FUTURE OF DEVELOPMENTAL METHODOLOGY.

    PubMed

    Little, Todd D; Wang, Eugene W; Gorrall, Britt K

    2017-06-01

    This chapter selectively reviews the evolution of quantitative practices in the field of developmental methodology. The chapter begins with an overview of the past in developmental methodology, discussing the implementation and dissemination of latent variable modeling and, in particular, longitudinal structural equation modeling. It then turns to the present state of developmental methodology, highlighting current methodological advances in the field. Additionally, this section summarizes ample quantitative resources, ranging from key quantitative methods journal articles to the various quantitative methods training programs and institutes. The chapter concludes with the future of developmental methodology and puts forth seven future innovations in the field. The innovations discussed span the topics of measurement, modeling, temporal design, and planned missing data designs. Lastly, the chapter closes with a brief overview of advanced modeling techniques such as continuous time models, state space models, and the application of Bayesian estimation in the field of developmental methodology. © 2017 The Society for Research in Child Development, Inc.

  16. GPS system simulation methodology

    NASA Technical Reports Server (NTRS)

    Ewing, Thomas F.

    1993-01-01

    The following topics are presented: background; Global Positioning System (GPS) methodology overview; the graphical user interface (GUI); current models; application to space nuclear power/propulsion; and interfacing requirements. The discussion is presented in vugraph form.

  17. Methodological quality of systematic reviews addressing femoroacetabular impingement.

    PubMed

    Kowalczuk, Marcin; Adamich, John; Simunovic, Nicole; Farrokhyar, Forough; Ayeni, Olufemi R

    2015-09-01

    As the body of literature on femoroacetabular impingement (FAI) continues to grow, clinicians turn to systematic reviews to remain current with the best available evidence. The quality of systematic reviews in the FAI literature is currently unknown. The goal of this study was to assess the quality of the reporting of systematic reviews addressing FAI over the last 11 years (2003-2014) and to identify the specific methodological shortcomings and strengths. A search of the electronic databases, MEDLINE, EMBASE and PubMed, was performed to identify relevant systematic reviews. Methodological quality was assessed by two reviewers using the revised assessment of multiple systematic reviews (R-AMSTAR) scoring tool. An intraclass correlation coefficient (ICC) with 95 % confidence intervals (CI) was used to determine agreement between reviewers on R-AMSTAR quality scores. A total of 22 systematic reviews were assessed for methodological quality. The mean consensus R-AMSTAR score across all studies was 26.7 out of 40.0, indicating fair methodological quality. An ICC of 0.931, 95 % CI 0.843-0.971 indicated excellent agreement between reviewers during the scoring process. The systematic reviews addressing FAI are generally of fair methodological quality. Use of tools such as the R-AMSTAR score or PRISMA guidelines while designing future systematic reviews can assist in eliminating methodological shortcomings identified in this review. These shortcomings need to be kept in mind by clinicians when applying the current literature to their patient populations and making treatment decisions. Systematic reviews of highest methodological quality should be used by clinicians when possible to answer clinical questions.

  18. Weapon Simulator Test Methodology Investigation: Comparison of Live Fire and Weapon Simulator Test Methodologies and the Effects of Clothing and Individual Equipment on Marksmanship

    DTIC Science & Technology

    2016-09-15

    METHODOLOGY INVESTIGATION: COMPARISON OF LIVE FIRE AND WEAPON SIMULATOR TEST METHODOLOGIES AND THE EFFECTS OF CLOTHING AND INDIVIDUAL EQUIPMENT ON...2. REPORT TYPE Final 3. DATES COVERED (From - To) October 2014 – August 2015 4. TITLE AND SUBTITLE WEAPON SIMULATOR TEST METHODOLOGY INVESTIGATION...COMPARISON OF LIVE FIRE AND WEAPON SIMULATOR TEST METHODOLOGIES AND THE EFFECTS OF CLOTHING AND INDIVIDUAL EQUIPMENT ON MARKSMANSHIP 5a. CONTRACT

  19. Discipline and Methodology in Higher Education Research

    ERIC Educational Resources Information Center

    Tight, Malcolm

    2013-01-01

    Higher education research is a multidisciplinary field, engaging researchers from across the academy who make use of a wide range of methodological approaches. This article examines the relation between discipline and methodology in higher education research, analysing a database of 567 articles published in 15 leading higher education journals…

  20. Advancing scoping study methodology: a web-based survey and consultation of perceptions on terminology, definition and methodological steps.

    PubMed

    O'Brien, Kelly K; Colquhoun, Heather; Levac, Danielle; Baxter, Larry; Tricco, Andrea C; Straus, Sharon; Wickerson, Lisa; Nayar, Ayesha; Moher, David; O'Malley, Lisa

    2016-07-26

    Scoping studies (or reviews) are a method used to comprehensively map evidence across a range of study designs in an area, with the aim of informing future research practice, programs and policy. However, no universal agreement exists on terminology, definition or methodological steps. Our aim was to understand the experiences of, and considerations for conducting scoping studies from the perspective of academic and community partners. Primary objectives were to 1) describe experiences conducting scoping studies including strengths and challenges; and 2) describe perspectives on terminology, definition, and methodological steps. We conducted a cross-sectional web-based survey with clinicians, educators, researchers, knowledge users, representatives from community-based organizations, graduate students, and policy stakeholders with experience and/or interest in conducting scoping studies to gain an understanding of experiences and perspectives on the conduct and reporting of scoping studies. We administered an electronic self-reported questionnaire comprised of 22 items related to experiences with scoping studies, strengths and challenges, opinions on terminology, and methodological steps. We analyzed questionnaire data using descriptive statistics and content analytical techniques. Survey results were discussed during a multi-stakeholder consultation to identify key considerations in the conduct and reporting of scoping studies. Of the 83 invitations, 54 individuals (65 %) completed the scoping questionnaire, and 48 (58 %) attended the scoping study meeting from Canada, the United Kingdom and United States. Many scoping study strengths were dually identified as challenges including breadth of scope, and iterative process. No consensus on terminology emerged, however key defining features that comprised a working definition of scoping studies included the exploratory mapping of literature in a field; iterative process, inclusion of grey literature; no quality

  1. Methodological Quality Assessment of Meta-Analyses of Hyperthyroidism Treatment.

    PubMed

    Qin, Yahong; Yao, Liang; Shao, Feifei; Yang, Kehu; Tian, Limin

    2018-01-01

    Hyperthyroidism is a common condition that is associated with increased morbidity and mortality. A number of meta-analyses (MAs) have assessed the therapeutic measures for hyperthyroidism, including antithyroid drugs, surgery, and radioiodine, however, the methodological quality has not been evaluated. This study evaluated the methodological quality and summarized the evidence obtained from MAs of hyperthyroidism treatments for radioiodine, antithyroid drugs, and surgery. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database databases. Two investigators independently assessed the meta-analyses titles and abstracts for inclusion. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. A total of 26 MAs fulfilled the inclusion criteria. Based on the AMSTAR scores, the average methodological quality was 8.31, with large variability ranging from 4 to 11. The methodological quality of English meta-analyses was better than that of Chinese meta-analyses. Cochrane reviews had better methodological quality than non-Cochrane reviews due to better study selection and data extraction, the inclusion of unpublished studies, and better reporting of study characteristics. The authors did not report conflicts of interest in 53.8% meta-analyses, and 19.2% did not report the harmful effects of treatment. Publication bias was not assessed in 38.5% of meta-analyses, and 19.2% did not report the follow-up time. Large-scale assessment of methodological quality of meta-analyses of hyperthyroidism treatment highlighted methodological strengths and weaknesses. Consideration of scientific quality when formulating conclusions should be made explicit. Future meta-analyses should improve on reporting conflict of interest. © Georg Thieme Verlag KG Stuttgart · New York.

  2. 45 CFR 98.101 - Case Review Methodology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Case Review Methodology. 98.101 Section 98.101 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Error Rate Reporting § 98.101 Case Review Methodology. (a) Case Reviews and Sampling—In preparing...

  3. 45 CFR 98.101 - Case Review Methodology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Case Review Methodology. 98.101 Section 98.101 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Error Rate Reporting § 98.101 Case Review Methodology. (a) Case Reviews and Sampling—In preparing...

  4. 45 CFR 98.101 - Case Review Methodology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Case Review Methodology. 98.101 Section 98.101 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Error Rate Reporting § 98.101 Case Review Methodology. (a) Case Reviews and Sampling—In preparing...

  5. 45 CFR 98.101 - Case Review Methodology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Case Review Methodology. 98.101 Section 98.101 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Error Rate Reporting § 98.101 Case Review Methodology. (a) Case Reviews and Sampling—In preparing...

  6. 45 CFR 98.101 - Case Review Methodology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Case Review Methodology. 98.101 Section 98.101 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Error Rate Reporting § 98.101 Case Review Methodology. (a) Case Reviews and Sampling—In preparing...

  7. ICCE/ICCAI 2000 Full & Short Papers (Methodologies).

    ERIC Educational Resources Information Center

    2000

    This document contains the full text of the following full and short papers on methodologies from ICCE/ICCAI 2000 (International Conference on Computers in Education/International Conference on Computer-Assisted Instruction): (1) "A Methodology for Learning Pattern Analysis from Web Logs by Interpreting Web Page Contents" (Chih-Kai Chang and…

  8. Methodology for evaluation of railroad technology research projects

    DOT National Transportation Integrated Search

    1981-04-01

    This Project memorandum presents a methodology for evaluating railroad research projects. The methodology includes consideration of industry and societal benefits, with special attention given to technical risks, implementation considerations, and po...

  9. Multiple Methodologies: Using Community-Based Participatory Research and Decolonizing Methodologies in Kenya

    ERIC Educational Resources Information Center

    Elder, Brent C.; Odoyo, Kenneth O.

    2018-01-01

    In this project, we examined the development of a sustainable inclusive education system in western Kenya by combining community-based participatory research (CBPR) and decolonizing methodologies. Through three cycles of qualitative interviews with stakeholders in inclusive education, participants explained what they saw as foundational components…

  10. Second Language Listening Strategy Research: Methodological Challenges and Perspectives

    ERIC Educational Resources Information Center

    Santos, Denise; Graham, Suzanne; Vanderplank, Robert

    2008-01-01

    This paper explores methodological issues related to research into second language listening strategies. We argue that a number of central questions regarding research methodology in this line of enquiry are underexamined, and we engage in the discussion of three key methodological questions: (1) To what extent is a verbal report a valid and…

  11. A Review of Citation Analysis Methodologies for Collection Management

    ERIC Educational Resources Information Center

    Hoffmann, Kristin; Doucette, Lise

    2012-01-01

    While there is a considerable body of literature that presents the results of citation analysis studies, most researchers do not provide enough detail in their methodology to reproduce the study, nor do they provide rationale for methodological decisions. In this paper, we review the methodologies used in 34 recent articles that present a…

  12. Supplement to a Methodology for Succession Planning for Technical Experts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kirk, Bernadette Lugue; Cain, Ronald A.; Agreda, Carla L.

    This report complements A Methodology for Succession Planning for Technical Experts (Ron Cain, Shaheen Dewji, Carla Agreda, Bernadette Kirk, July 2017), which describes a draft methodology for identifying and evaluating the loss of key technical skills at nuclear operations facilities. This report targets the methodology for identifying critical skills, and the methodology is tested through interviews with selected subject matter experts.

  13. Methodology for astronaut reconditioning research.

    PubMed

    Beard, David J; Cook, Jonathan A

    2017-01-01

    Space medicine offers some unique challenges, especially in terms of research methodology. A specific challenge for astronaut reconditioning involves identification of what aspects of terrestrial research methodology hold and which require modification. This paper reviews this area and presents appropriate solutions where possible. It is concluded that spaceflight rehabilitation research should remain question/problem driven and is broadly similar to the terrestrial equivalent on small populations, such as rare diseases and various sports. Astronauts and Medical Operations personnel should be involved at all levels to ensure feasibility of research protocols. There is room for creative and hybrid methodology but careful systematic observation is likely to be more achievable and fruitful than complex trial based comparisons. Multi-space agency collaboration will be critical to pool data from small groups of astronauts with the accepted use of standardised outcome measures across all agencies. Systematic reviews will be an essential component. Most limitations relate to the inherent small sample size available for human spaceflight research. Early adoption of a co-operative model for spaceflight rehabilitation research is therefore advised. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Methodological quality of systematic reviews on influenza vaccination.

    PubMed

    Remschmidt, Cornelius; Wichmann, Ole; Harder, Thomas

    2014-03-26

    There is a growing body of evidence on the risks and benefits of influenza vaccination in various target groups. Systematic reviews are of particular importance for policy decisions. However, their methodological quality can vary considerably. To investigate the methodological quality of systematic reviews on influenza vaccination (efficacy, effectiveness, safety) and to identify influencing factors. A systematic literature search on systematic reviews on influenza vaccination was performed, using MEDLINE, EMBASE and three additional databases (1990-2013). Review characteristics were extracted and the methodological quality of the reviews was evaluated using the assessment of multiple systematic reviews (AMSTAR) tool. U-test, Kruskal-Wallis test, chi-square test, and multivariable linear regression analysis were used to assess the influence of review characteristics on AMSTAR-score. Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high (median AMSTAR-score: 8), but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). Detailed analysis showed that this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05). In the adjusted analysis, no other factor, including industry sponsorship or journal impact factor had an influence on AMSTAR score. Systematic reviews on influenza vaccination showed large differences regarding their methodological quality. Reviews conducted by the Cochrane collaboration were of higher quality than others. When using systematic reviews to guide the development of vaccination recommendations, the methodological quality of a review in addition to its content should be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A methodology for boost-glide transport technology planning

    NASA Technical Reports Server (NTRS)

    Repic, E. M.; Olson, G. A.; Milliken, R. J.

    1974-01-01

    A systematic procedure is presented by which the relative economic value of technology factors affecting design, configuration, and operation of boost-glide transport can be evaluated. Use of the methodology results in identification of first-order economic gains potentially achievable by projected advances in each of the definable, hypersonic technologies. Starting with a baseline vehicle, the formulas, procedures and forms which are integral parts of this methodology are developed. A demonstration of the methodology is presented for one specific boost-glide system.

  16. New methodologies for patients rehabilitation.

    PubMed

    Fardoun, H M; Mashat, A S; Lange, B

    2015-01-01

    The present editorial is part of the focus theme of Methods of Information in Medicine titled "New Methodologies for Patients Rehabilitation", with a specific focus on technologies and human factors related to the use of Information and Communication Technologies (ICT) for improving patient rehabilitation. The focus theme explores different dimensions of empowerment methodologies for disabled people in terms of rehabilitation and health care, and to explores the extent to which ICT is a useful tool in this process. The focus theme lists a set of research papers that present different ways of using ICT to develop advanced systems that help disabled people in their rehabilitation process.

  17. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  18. Improving Learning Outcome Using Six Sigma Methodology

    ERIC Educational Resources Information Center

    Tetteh, Godson A.

    2015-01-01

    Purpose: The purpose of this research paper is to apply the Six Sigma methodology to identify the attributes of a lecturer that will help improve a student's prior knowledge of a discipline from an initial "x" per cent knowledge to a higher "y" per cent of knowledge. Design/methodology/approach: The data collection method…

  19. Methodology to Estimate the Quantity, Composition, and ...

    EPA Pesticide Factsheets

    This report, Methodology to Estimate the Quantity, Composition and Management of Construction and Demolition Debris in the US, was developed to expand access to data on CDD in the US and to support research on CDD and sustainable materials management. Since past US EPA CDD estimates have been limited to building-related CDD, a goal in the development of this methodology was to use data originating from CDD facilities and contractors to better capture the current picture of total CDD management, including materials from roads, bridges and infrastructure. This report, Methodology to Estimate the Quantity, Composition and Management of Construction and Demolition Debris in the US, was developed to expand access to data on CDD in the US and to support research on CDD and sustainable materials management. Since past US EPA CDD estimates have been limited to building-related CDD, a goal in the development of this methodology was to use data originating from CDD facilities and contractors to better capture the current picture of total CDD management, including materials from roads, bridges and infrastructure.

  20. Transportation networks : data, analysis, methodology development and visualization.

    DOT National Transportation Integrated Search

    2007-12-29

    This project provides data compilation, analysis methodology and visualization methodology for the current network : data assets of the Alabama Department of Transportation (ALDOT). This study finds that ALDOT is faced with a : considerable number of...

  1. Risk Assessment Methodology for Hazardous Waste Management (1998)

    EPA Pesticide Factsheets

    A methodology is described for systematically assessing and comparing the risks to human health and the environment of hazardous waste management alternatives. The methodology selects and links appropriate models and techniques for performing the process.

  2. Applying a contemporary grounded theory methodology.

    PubMed

    Licqurish, Sharon; Seibold, Carmel

    2011-01-01

    The aim of this paper is to discuss the application of a contemporary grounded theory methodology to a research project exploring the experiences of students studying for a degree in midwifery. Grounded theory is a qualitative research approach developed by Glaser and Strauss in the 1950s but the methodology for this study was modelled on Clarke's (2005) approach and was underpinned by a symbolic interactionist theoretical perspective, post-structuralist theories of Michel Foucault and a constructionist epistemology. The study participants were 19 midwifery students completing their final placement. Data were collected through individual in-depth interviews and participant observation, and analysed using the grounded theory analysis techniques of coding, constant comparative analysis and theoretical sampling, as well as situational maps. The analysis focused on social action and interaction and the operation of power in the students' environment. The social process in which the students were involved, as well as the actors and discourses that affected the students' competency development, were highlighted. The methodology allowed a thorough exploration of the students' experiences of achieving competency. However, some difficulties were encountered. One of the major issues related to the understanding and application of complex sociological theories that challenged positivist notions of truth and power. Furthermore, the mapping processes were complex. Despite these minor challenges, the authors recommend applying this methodology to other similar research projects.

  3. Symbiotic empirical ethics: a practical methodology.

    PubMed

    Frith, Lucy

    2012-05-01

    Like any discipline, bioethics is a developing field of academic inquiry; and recent trends in scholarship have been towards more engagement with empirical research. This 'empirical turn' has provoked extensive debate over how such 'descriptive' research carried out in the social sciences contributes to the distinctively normative aspect of bioethics. This paper will address this issue by developing a practical research methodology for the inclusion of data from social science studies into ethical deliberation. This methodology will be based on a naturalistic conception of ethical theory that sees practice as informing theory just as theory informs practice - the two are symbiotically related. From this engagement with practice, the ways that such theories need to be extended and developed can be determined. This is a practical methodology for integrating theory and practice that can be used in empirical studies, one that uses ethical theory both to explore the data and to draw normative conclusions. © 2010 Blackwell Publishing Ltd.

  4. Methodology of management of dredging operations II. Applications.

    PubMed

    Junqua, G; Abriak, N E; Gregoire, P; Dubois, V; Mac Farlane, F; Damidot, D

    2006-04-01

    This paper presents the new methodology of management of dredging operations. Derived partly from existing methodologies (OECD, PNUE, AIPCN), it aims to be more comprehensive, mixing the qualities and the complementarities of previous methodologies. The application of the methodology has been carried out on the site of the Port of Dunkirk (FRANCE). Thus, a characterization of the sediments of this site has allowed a zoning of the Port to be established in to zones of probable homogeneity of sediments. Moreover, sources of pollution have been identified, with an aim of prevention. Ways of waste improvement have also been developed, to answer regional needs, from a point of view of competitive and territorial intelligence. Their development has required a mutualisation of resources between professionals, research centres and local communities, according to principles of industrial ecology. Lastly, a tool of MultiCriteria Decision-Making Aid (M.C.D.M.A.) has been used to determine the most relevant scenario (or alternative, or action) for a dredging operation intended by the Port of Dunkirk. These applications have confirmed the relevance of this methodology for the management of dredging operations.

  5. A methodology for collecting valid software engineering data

    NASA Technical Reports Server (NTRS)

    Basili, Victor R.; Weiss, David M.

    1983-01-01

    An effective data collection method for evaluating software development methodologies and for studying the software development process is described. The method uses goal-directed data collection to evaluate methodologies with respect to the claims made for them. Such claims are used as a basis for defining the goals of the data collection, establishing a list of questions of interest to be answered by data analysis, defining a set of data categorization schemes, and designing a data collection form. The data to be collected are based on the changes made to the software during development, and are obtained when the changes are made. To insure accuracy of the data, validation is performed concurrently with software development and data collection. Validation is based on interviews with those people supplying the data. Results from using the methodology show that data validation is a necessary part of change data collection. Without it, as much as 50% of the data may be erroneous. Feasibility of the data collection methodology was demonstrated by applying it to five different projects in two different environments. The application showed that the methodology was both feasible and useful.

  6. METHODOLOGICAL QUALITY OF ECONOMIC EVALUATIONS ALONGSIDE TRIALS OF KNEE PHYSIOTHERAPY.

    PubMed

    García-Pérez, Lidia; Linertová, Renata; Arvelo-Martín, Alejandro; Guerra-Marrero, Carolina; Martínez-Alberto, Carlos Enrique; Cuéllar-Pompa, Leticia; Escobar, Antonio; Serrano-Aguilar, Pedro

    2017-01-01

    The methodological quality of an economic evaluation performed alongside a clinical trial can be underestimated if the paper does not report key methodological features. This study discusses methodological assessment issues on the example of a systematic review on cost-effectiveness of physiotherapy for knee osteoarthritis. Six economic evaluation studies included in the systematic review and related clinical trials were assessed using the 10-question check-list by Drummond and the Physiotherapy Evidence Database (PEDro) scale. All economic evaluations were performed alongside a clinical trial but the studied interventions were too heterogeneous to be synthesized. Methodological quality of the economic evaluations reported in the papers was not free of drawbacks, and in some cases, it improved when information from the related clinical trial was taken into account. Economic evaluation papers dedicate little space to methodological features of related clinical trials; therefore, the methodological quality can be underestimated if evaluated separately from the trials. Future economic evaluations should follow more strictly the recommendations about methodology and the authors should pay special attention to the quality of reporting.

  7. Differing antidepressant maintenance methodologies.

    PubMed

    Safer, Daniel J

    2017-10-01

    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

  8. Development of economic consequence methodology for process risk analysis.

    PubMed

    Zadakbar, Omid; Khan, Faisal; Imtiaz, Syed

    2015-04-01

    A comprehensive methodology for economic consequence analysis with appropriate models for risk analysis of process systems is proposed. This methodology uses loss functions to relate process deviations in a given scenario to economic losses. It consists of four steps: definition of a scenario, identification of losses, quantification of losses, and integration of losses. In this methodology, the process deviations that contribute to a given accident scenario are identified and mapped to assess potential consequences. Losses are assessed with an appropriate loss function (revised Taguchi, modified inverted normal) for each type of loss. The total loss is quantified by integrating different loss functions. The proposed methodology has been examined on two industrial case studies. Implementation of this new economic consequence methodology in quantitative risk assessment will provide better understanding and quantification of risk. This will improve design, decision making, and risk management strategies. © 2014 Society for Risk Analysis.

  9. Optimized planning methodologies of ASON implementation

    NASA Astrophysics Data System (ADS)

    Zhou, Michael M.; Tamil, Lakshman S.

    2005-02-01

    Advanced network planning concerns effective network-resource allocation for dynamic and open business environment. Planning methodologies of ASON implementation based on qualitative analysis and mathematical modeling are presented in this paper. The methodology includes method of rationalizing technology and architecture, building network and nodal models, and developing dynamic programming for multi-period deployment. The multi-layered nodal architecture proposed here can accommodate various nodal configurations for a multi-plane optical network and the network modeling presented here computes the required network elements for optimizing resource allocation.

  10. Research methodology in recurrent pregnancy loss.

    PubMed

    Christiansen, Ole B

    2014-03-01

    The aim of this article is to highlight pitfalls in research methodology that may explain why studies in recurrent pregnancy loss (RPL) often provide very divergent results. It is hoped that insight into this issue may help clinicians decide which published studies are the most valid. It may help researchers to eliminate methodological flaws in future studies, which may hopefully come to some kind of agreement about the usefulness of diagnostic tests and treatments in RPL. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Health economic evaluation: important principles and methodology.

    PubMed

    Rudmik, Luke; Drummond, Michael

    2013-06-01

    To discuss health economic evaluation and improve the understanding of common methodology. This article discusses the methodology for the following types of economic evaluations: cost-minimization, cost-effectiveness, cost-utility, cost-benefit, and economic modeling. Topics include health-state utility measures, the quality-adjusted life year (QALY), uncertainty analysis, discounting, decision tree analysis, and Markov modeling. Economic evaluation is the comparative analysis of alternative courses of action in terms of both their costs and consequences. With increasing health care expenditure and limited resources, it is important for physicians to consider the economic impact of their interventions. Understanding common methodology involved in health economic evaluation will improve critical appraisal of the literature and optimize future economic evaluations. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides.

    PubMed

    Qiu, Guanyinsheng; Wu, Jie

    2016-02-01

    As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. A Nursing Process Methodology.

    ERIC Educational Resources Information Center

    Ryan-Wenger, Nancy M.

    1990-01-01

    A nursing methodology developed by the faculty at The Ohio State University teaches nursing students problem-solving techniques applicable to any nursing situation. It also provides faculty and students with a basis for measuring students' progress and ability in applying the nursing process. (Author)

  14. Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun

    Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Here in this study, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced numbermore » of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.« less

  15. Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

    DOE PAGES

    Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun; ...

    2017-03-13

    Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Here in this study, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced numbermore » of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.« less

  16. Examining emotional expressions in discourse: methodological considerations

    NASA Astrophysics Data System (ADS)

    Hufnagel, Elizabeth; Kelly, Gregory J.

    2017-10-01

    This methodological paper presents an approach for examining emotional expressions through discourse analysis and ethnographic methods. Drawing on trends in the current literature in science education, we briefly explain the importance of emotions in science education and examine the current research methodologies used in interactional emotion studies. We put forth and substantiate a methodological approach that attends to the interactional, contextual, intertextual, and consequential aspects of emotional expressions. By examining emotional expressions in the discourse in which they are constructed, emotional expressions are identified through semantics, contextualization, and linguistic features. These features make salient four dimensions of emotional expressions: aboutness, frequency, type, and ownership. Drawing on data from a large empirical study of pre-service elementary teachers' emotional expressions about climate change in a science course, we provide illustrative examples to describe what counts as emotional expressions in situ. In doing so we explain how our approach makes salient the nuanced nature of such expressions as well as the broader discourse in which they are constructed and the implications for researching emotional expressions in science education discourse. We suggest reasons why this discourse orientated research methodology can contribute to the interactional study of emotions in science education contexts.

  17. Essential methodological considerations when using grounded theory.

    PubMed

    Achora, Susan; Matua, Gerald Amandu

    2016-07-01

    To suggest important methodological considerations when using grounded theory. A research method widely used in nursing research is grounded theory, at the centre of which is theory construction. However, researchers still struggle with some of its methodological issues. Although grounded theory is widely used to study and explain issues in nursing practice, many researchers are still failing to adhere to its rigorous standards. Researchers should articulate the focus of their investigations - the substantive area of interest as well as the focal population. This should be followed by a succinct explanation of the strategies used to collect and analyse data, supported by clear coding processes. Finally, the resolution of the core issues, including the core category and related categories, should be explained to advance readers' understanding. Researchers should endeavour to understand the tenets of grounded theory. This enables 'neophytes' in particular to make methodological decisions that will improve their studies' rigour and fit with grounded theory. This paper complements the current dialogue on improving the understanding of grounded theory methodology in nursing research. The paper also suggests important procedural decisions researchers need to make to preserve their studies' scientific merit and fit with grounded theory.

  18. A Generalizable Methodology for Quantifying User Satisfaction

    NASA Astrophysics Data System (ADS)

    Huang, Te-Yuan; Chen, Kuan-Ta; Huang, Polly; Lei, Chin-Laung

    Quantifying user satisfaction is essential, because the results can help service providers deliver better services. In this work, we propose a generalizable methodology, based on survival analysis, to quantify user satisfaction in terms of session times, i. e., the length of time users stay with an application. Unlike subjective human surveys, our methodology is based solely on passive measurement, which is more cost-efficient and better able to capture subconscious reactions. Furthermore, by using session times, rather than a specific performance indicator, such as the level of distortion of voice signals, the effects of other factors like loudness and sidetone, can also be captured by the developed models. Like survival analysis, our methodology is characterized by low complexity and a simple model-developing process. The feasibility of our methodology is demonstrated through case studies of ShenZhou Online, a commercial MMORPG in Taiwan, and the most prevalent VoIP application in the world, namely Skype. Through the model development process, we can also identify the most significant performance factors and their impacts on user satisfaction and discuss how they can be exploited to improve user experience and optimize resource allocation.

  19. Towards Methodologies for Building Knowledge-Based Instructional Systems.

    ERIC Educational Resources Information Center

    Duchastel, Philippe

    1992-01-01

    Examines the processes involved in building instructional systems that are based on artificial intelligence and hypermedia technologies. Traditional instructional systems design methodology is discussed; design issues including system architecture and learning strategies are addressed; and a new methodology for building knowledge-based…

  20. On the Unification of Psychology, Methodology, and Pedagogy.

    ERIC Educational Resources Information Center

    Wettersten, John

    1987-01-01

    The psychological and methodological bases of the Agassi teaching method are described to provide a context for evaluating the theory. A brief history of Selzian psychology and Popper's methodology is given. The Agassi method, which stresses learning through questioning, is detailed. (JL)

  1. Common Methodological Problems in Research on the Addictions.

    ERIC Educational Resources Information Center

    Nathan, Peter E.; Lansky, David

    1978-01-01

    Identifies common problems in research on the addictions and offers suggestions for remediating these methodological problems. The addictions considered include alcoholism and drug dependencies. Problems considered are those arising from inadequate, incomplete, or biased reviews of relevant literatures and methodological shortcomings of subject…

  2. The need for a comprehensive expert system development methodology

    NASA Technical Reports Server (NTRS)

    Baumert, John; Critchfield, Anna; Leavitt, Karen

    1988-01-01

    In a traditional software development environment, the introduction of standardized approaches has led to higher quality, maintainable products on the technical side and greater visibility into the status of the effort on the management side. This study examined expert system development to determine whether it differed enough from traditional systems to warrant a reevaluation of current software development methodologies. Its purpose was to identify areas of similarity with traditional software development and areas requiring tailoring to the unique needs of expert systems. A second purpose was to determine whether existing expert system development methodologies meet the needs of expert system development, management, and maintenance personnel. The study consisted of a literature search and personal interviews. It was determined that existing methodologies and approaches to developing expert systems are not comprehensive nor are they easily applied, especially to cradle to grave system development. As a result, requirements were derived for an expert system development methodology and an initial annotated outline derived for such a methodology.

  3. A hierarchical clustering methodology for the estimation of toxicity.

    PubMed

    Martin, Todd M; Harten, Paul; Venkatapathy, Raghuraman; Das, Shashikala; Young, Douglas M

    2008-01-01

    ABSTRACT A quantitative structure-activity relationship (QSAR) methodology based on hierarchical clustering was developed to predict toxicological endpoints. This methodology utilizes Ward's method to divide a training set into a series of structurally similar clusters. The structural similarity is defined in terms of 2-D physicochemical descriptors (such as connectivity and E-state indices). A genetic algorithm-based technique is used to generate statistically valid QSAR models for each cluster (using the pool of descriptors described above). The toxicity for a given query compound is estimated using the weighted average of the predictions from the closest cluster from each step in the hierarchical clustering assuming that the compound is within the domain of applicability of the cluster. The hierarchical clustering methodology was tested using a Tetrahymena pyriformis acute toxicity data set containing 644 chemicals in the training set and with two prediction sets containing 339 and 110 chemicals. The results from the hierarchical clustering methodology were compared to the results from several different QSAR methodologies.

  4. Rater methodology for stroboscopy: a systematic review.

    PubMed

    Bonilha, Heather Shaw; Focht, Kendrea L; Martin-Harris, Bonnie

    2015-01-01

    Laryngeal endoscopy with stroboscopy (LES) remains the clinical gold standard for assessing vocal fold function. LES is used to evaluate the efficacy of voice treatments in research studies and clinical practice. LES as a voice treatment outcome tool is only as good as the clinician interpreting the recordings. Research using LES as a treatment outcome measure should be evaluated based on rater methodology and reliability. The purpose of this literature review was to evaluate the rater-related methodology from studies that use stroboscopic findings as voice treatment outcome measures. Systematic literature review. Computerized journal databases were searched for relevant articles using terms: stroboscopy and treatment. Eligible articles were categorized and evaluated for the use of rater-related methodology, reporting of number of raters, types of raters, blinding, and rater reliability. Of the 738 articles reviewed, 80 articles met inclusion criteria. More than one-third of the studies included in the review did not report the number of raters who participated in the study. Eleven studies reported results of rater reliability analysis with only two studies reporting good inter- and intrarater reliability. The comparability and use of results from treatment studies that use LES are limited by a lack of rigor in rater methodology and variable, mostly poor, inter- and intrarater reliability. To improve our ability to evaluate and use the findings from voice treatment studies that use LES features as outcome measures, greater consistency of reporting rater methodology characteristics across studies and improved rater reliability is needed. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  5. Diels-Alder reactions of five-membered heterocycles containing one heteroatom

    PubMed Central

    Ding, Xiaoyuan; Nguyen, Son T.; Williams, John D.; Peet, Norton P.

    2015-01-01

    Diels-Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6). PMID:25838605

  6. K-Means Subject Matter Expert Refined Topic Model Methodology

    DTIC Science & Technology

    2017-01-01

    Refined Topic Model Methodology Topic Model Estimation via K-Means U.S. Army TRADOC Analysis Center-Monterey 700 Dyer Road...January 2017 K-means Subject Matter Expert Refined Topic Model Methodology Topic Model Estimation via K-Means Theodore T. Allen, Ph.D. Zhenhuan...Matter Expert Refined Topic Model Methodology Topic Model Estimation via K-means 5a. CONTRACT NUMBER W9124N-15-P-0022 5b. GRANT NUMBER 5c

  7. Tobacco documents research methodology

    PubMed Central

    McCandless, Phyra M; Klausner, Kim; Taketa, Rachel; Yerger, Valerie B

    2011-01-01

    Tobacco documents research has developed into a thriving academic enterprise since its inception in 1995. The technology supporting tobacco documents archiving, searching and retrieval has improved greatly since that time, and consequently tobacco documents researchers have considerably more access to resources than was the case when researchers had to travel to physical archives and/or electronically search poorly and incompletely indexed documents. The authors of the papers presented in this supplement all followed the same basic research methodology. Rather than leave the reader of the supplement to read the same discussion of methods in each individual paper, presented here is an overview of the methods all authors followed. In the individual articles that follow in this supplement, the authors present the additional methodological information specific to their topics. This brief discussion also highlights technological capabilities in the Legacy Tobacco Documents Library and updates methods for organising internal tobacco documents data and findings. PMID:21504933

  8. Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations.

    PubMed

    Cao, Jun

    2015-06-28

    In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π(*) transition induces a cleavage of the C-N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π(*) excitation of the imine chromophore results in a cleavage of the C-C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N-O bond cleavages on both S1((1)ππ(*)) and S2((1)nNπ(*)) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

  9. Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations

    NASA Astrophysics Data System (ADS)

    Cao, Jun

    2015-06-01

    In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π* transition induces a cleavage of the C—N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π* excitation of the imine chromophore results in a cleavage of the C—C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N—O bond cleavages on both S1(1ππ*) and S2(1nNπ*) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

  10. Teaching Labor Market Survey Methodology in Rehabilitation Counseling

    ERIC Educational Resources Information Center

    Barros-Bailey, Mary

    2012-01-01

    Labor Market Survey (LMS) and labor market analysis knowledge and methodologies are minimum competencies expected of rehabilitation counselors through credentialing and accreditation boards. However, LMS knowledge and methodology is an example of a contemporary oral tradition that is universally recognized in rehabilitation and disability services…

  11. Learning Methodology in the Classroom to Encourage Participation

    ERIC Educational Resources Information Center

    Luna, Esther; Folgueiras, Pilar

    2014-01-01

    Service learning is a methodology that promotes the participation of citizens in their community. This article presents a brief conceptualization of citizen participation, characteristics of service learning methodology, and validation of a programme that promotes service-learning projects. This validation highlights the suitability of this…

  12. Analysis and methodology for aeronautical systems technology program planning

    NASA Technical Reports Server (NTRS)

    White, M. J.; Gershkoff, I.; Lamkin, S.

    1983-01-01

    A structured methodology was developed that allows the generation, analysis, and rank-ordering of system concepts by their benefits and costs, indicating the preferred order of implementation. The methodology is supported by a base of data on civil transport aircraft fleet growth projections and data on aircraft performance relating the contribution of each element of the aircraft to overall performance. The performance data are used to assess the benefits of proposed concepts. The methodology includes a computer program for performing the calculations needed to rank-order the concepts and compute their cumulative benefit-to-cost ratio. The use of the methodology and supporting data is illustrated through the analysis of actual system concepts from various sources.

  13. Methodology issues in implementation science.

    PubMed

    Newhouse, Robin; Bobay, Kathleen; Dykes, Patricia C; Stevens, Kathleen R; Titler, Marita

    2013-04-01

    Putting evidence into practice at the point of care delivery requires an understanding of implementation strategies that work, in what context and how. To identify methodological issues in implementation science using 4 studies as cases and make recommendations for further methods development. Four cases are presented and methodological issues identified. For each issue raised, evidence on the state of the science is described. Issues in implementation science identified include diverse conceptual frameworks, potential weaknesses in pragmatic study designs, and the paucity of standard concepts and measurement. Recommendations to advance methods in implementation include developing a core set of implementation concepts and metrics, generating standards for implementation methods including pragmatic trials, mixed methods designs, complex interventions and measurement, and endorsing reporting standards for implementation studies.

  14. Methodological update in Medicina Intensiva.

    PubMed

    García Garmendia, J L

    2018-04-01

    Research in the critically ill is complex by the heterogeneity of patients, the difficulties to achieve representative sample sizes and the number of variables simultaneously involved. However, the quantity and quality of records is high as well as the relevance of the variables used, such as survival. The methodological tools have evolved to offering new perspectives and analysis models that allow extracting relevant information from the data that accompanies the critically ill patient. The need for training in methodology and interpretation of results is an important challenge for the intensivists who wish to be updated on the research developments and clinical advances in Intensive Medicine. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  15. Behavior Analysis: Methodological Foundations.

    ERIC Educational Resources Information Center

    Owen, James L.

    Behavior analysis provides a unique way of coming to understand intrapersonal and interpersonal communication behaviors, and focuses on control techniques available to a speaker and counter-control techniques available to a listener. "Time-series methodology" is a convenient term because it subsumes under one label a variety of baseline…

  16. Space Transportation Operations: Assessment of Methodologies and Models

    NASA Technical Reports Server (NTRS)

    Joglekar, Prafulla

    2001-01-01

    The systems design process for future space transportation involves understanding multiple variables and their effect on lifecycle metrics. Variables such as technology readiness or potential environmental impact are qualitative, while variables such as reliability, operations costs or flight rates are quantitative. In deciding what new design concepts to fund, NASA needs a methodology that would assess the sum total of all relevant qualitative and quantitative lifecycle metrics resulting from each proposed concept. The objective of this research was to review the state of operations assessment methodologies and models used to evaluate proposed space transportation systems and to develop recommendations for improving them. It was found that, compared to the models available from other sources, the operations assessment methodology recently developed at Kennedy Space Center has the potential to produce a decision support tool that will serve as the industry standard. Towards that goal, a number of areas of improvement in the Kennedy Space Center's methodology are identified.

  17. Space Transportation Operations: Assessment of Methodologies and Models

    NASA Technical Reports Server (NTRS)

    Joglekar, Prafulla

    2002-01-01

    The systems design process for future space transportation involves understanding multiple variables and their effect on lifecycle metrics. Variables such as technology readiness or potential environmental impact are qualitative, while variables such as reliability, operations costs or flight rates are quantitative. In deciding what new design concepts to fund, NASA needs a methodology that would assess the sum total of all relevant qualitative and quantitative lifecycle metrics resulting from each proposed concept. The objective of this research was to review the state of operations assessment methodologies and models used to evaluate proposed space transportation systems and to develop recommendations for improving them. It was found that, compared to the models available from other sources, the operations assessment methodology recently developed at Kennedy Space Center has the potential to produce a decision support tool that will serve as the industry standard. Towards that goal, a number of areas of improvement in the Kennedy Space Center's methodology are identified.

  18. Integration of infrared thermography into various maintenance methodologies

    NASA Astrophysics Data System (ADS)

    Morgan, William T.

    1993-04-01

    Maintenance methodologies are in developmental stages throughout the world as global competitiveness drives all industries to improve operational efficiencies. Rapid progress in technical advancements has added an additional strain on maintenance organizations to progressively change. Accompanying needs for advanced training and documentation is the demand for utilization of various analytical instruments and quantitative methods. Infrared thermography is one of the primary elements of engineered approaches to maintenance. Current maintenance methodologies can be divided into six categories; Routine ('Breakdown'), Preventive, Predictive, Proactive, Reliability-Based, and Total Productive (TPM) maintenance. Each of these methodologies have distinctive approaches to achieving improved operational efficiencies. Popular though is that infrared thermography is a Predictive maintenance tool. While this is true, it is also true that it can be effectively integrated into each of the maintenance methodologies for achieving desired results. The six maintenance strategies will be defined. Infrared applications integrated into each will be composed in tabular form.

  19. The ethics of placebo-controlled trials: methodological justifications.

    PubMed

    Millum, Joseph; Grady, Christine

    2013-11-01

    The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling. © 2013.

  20. A comparison of results of empirical studies of supplementary search techniques and recommendations in review methodology handbooks: a methodological review.

    PubMed

    Cooper, Chris; Booth, Andrew; Britten, Nicky; Garside, Ruth

    2017-11-28

    The purpose and contribution of supplementary search methods in systematic reviews is increasingly acknowledged. Numerous studies have demonstrated their potential in identifying studies or study data that would have been missed by bibliographic database searching alone. What is less certain is how supplementary search methods actually work, how they are applied, and the consequent advantages, disadvantages and resource implications of each search method. The aim of this study is to compare current practice in using supplementary search methods with methodological guidance. Four methodological handbooks in informing systematic review practice in the UK were read and audited to establish current methodological guidance. Studies evaluating the use of supplementary search methods were identified by searching five bibliographic databases. Studies were included if they (1) reported practical application of a supplementary search method (descriptive) or (2) examined the utility of a supplementary search method (analytical) or (3) identified/explored factors that impact on the utility of a supplementary method, when applied in practice. Thirty-five studies were included in this review in addition to the four methodological handbooks. Studies were published between 1989 and 2016, and dates of publication of the handbooks ranged from 1994 to 2014. Five supplementary search methods were reviewed: contacting study authors, citation chasing, handsearching, searching trial registers and web searching. There is reasonable consistency between recommended best practice (handbooks) and current practice (methodological studies) as it relates to the application of supplementary search methods. The methodological studies provide useful information on the effectiveness of the supplementary search methods, often seeking to evaluate aspects of the method to improve effectiveness or efficiency. In this way, the studies advance the understanding of the supplementary search methods. Further

  1. Methodological Review of Intimate Partner Violence Prevention Research

    ERIC Educational Resources Information Center

    Murray, Christine E.; Graybeal, Jennifer

    2007-01-01

    The authors present a methodological review of empirical program evaluation research in the area of intimate partner violence prevention. The authors adapted and utilized criterion-based rating forms to standardize the evaluation of the methodological strengths and weaknesses of each study. The findings indicate that the limited amount of…

  2. Posthumanism as Research Methodology: Inquiry in the Anthropocene

    ERIC Educational Resources Information Center

    Ulmer, Jasmine B.

    2017-01-01

    The posthuman turn has radically--and rapidly--shifted what is possible in research methodology. In response, my aim in this conceptual paper is to suggest entry points into posthuman educational research methodology. I outline aspects of posthumanism while recognizing its multiplicity: there are many posthumanisms and each offers different…

  3. Representation of Scientific Methodology in Secondary Science Textbooks

    ERIC Educational Resources Information Center

    Binns, Ian C.; Bell, Randy L.

    2015-01-01

    This study explored how eight widely used secondary science textbooks described scientific methodology and to what degree the textbooks' examples and investigations were consistent with this description. Data consisted of all text from student and teacher editions that referred to scientific methodology and all investigations. Analysis used an…

  4. Do we need methodological theory to do qualitative research?

    PubMed

    Avis, Mark

    2003-09-01

    Positivism is frequently used to stand for the epistemological assumption that empirical science based on principles of verificationism, objectivity, and reproducibility is the foundation of all genuine knowledge. Qualitative researchers sometimes feel obliged to provide methodological alternatives to positivism that recognize their different ethical, ontological, and epistemological commitments and have provided three theories: phenomenology, grounded theory, and ethnography. The author argues that positivism was a doomed attempt to define empirical foundations for knowledge through a rigorous separation of theory and evidence; offers a pragmatic, coherent view of knowledge; and suggests that rigorous, rational empirical investigation does not need methodological theory. Therefore, qualitative methodological theory is unnecessary and counterproductive because it hinders critical reflection on the relation between methodological theory and empirical evidence.

  5. Methodological rigor and citation frequency in patient compliance literature.

    PubMed Central

    Bruer, J T

    1982-01-01

    An exhaustive bibliography which assesses the methodological rigor of the patient compliance literature, and citation data from the Science Citation Index (SCI) are combined to determine if methodologically rigorous papers are used with greater frequency than substandard articles by compliance investigators. There are low, but statistically significant, correlations between methodological rigor and citation indicators for 138 patient compliance papers published in SCI source journals during 1975 and 1976. The correlation is not strong enough to warrant use of citation measures as indicators of rigor on a paper-by-paper basis. The data do suggest that citation measures might be developed as crude indicators of methodological rigor. There is no evidence that randomized trials are cited more frequently than studies that employ other experimental designs. PMID:7114334

  6. A Design Methodology for Medical Processes.

    PubMed

    Ferrante, Simona; Bonacina, Stefano; Pozzi, Giuseppe; Pinciroli, Francesco; Marceglia, Sara

    2016-01-01

    Healthcare processes, especially those belonging to the clinical domain, are acknowledged as complex and characterized by the dynamic nature of the diagnosis, the variability of the decisions made by experts driven by their experiences, the local constraints, the patient's needs, the uncertainty of the patient's response, and the indeterminacy of patient's compliance to treatment. Also, the multiple actors involved in patient's care need clear and transparent communication to ensure care coordination. In this paper, we propose a methodology to model healthcare processes in order to break out complexity and provide transparency. The model is grounded on a set of requirements that make the healthcare domain unique with respect to other knowledge domains. The modeling methodology is based on three main phases: the study of the environmental context, the conceptual modeling, and the logical modeling. The proposed methodology was validated by applying it to the case study of the rehabilitation process of stroke patients in the specific setting of a specialized rehabilitation center. The resulting model was used to define the specifications of a software artifact for the digital administration and collection of assessment tests that was also implemented. Despite being only an example, our case study showed the ability of process modeling to answer the actual needs in healthcare practices. Independently from the medical domain in which the modeling effort is done, the proposed methodology is useful to create high-quality models, and to detect and take into account relevant and tricky situations that can occur during process execution.

  7. A Design Methodology for Medical Processes

    PubMed Central

    Bonacina, Stefano; Pozzi, Giuseppe; Pinciroli, Francesco; Marceglia, Sara

    2016-01-01

    Summary Background Healthcare processes, especially those belonging to the clinical domain, are acknowledged as complex and characterized by the dynamic nature of the diagnosis, the variability of the decisions made by experts driven by their experiences, the local constraints, the patient’s needs, the uncertainty of the patient’s response, and the indeterminacy of patient’s compliance to treatment. Also, the multiple actors involved in patient’s care need clear and transparent communication to ensure care coordination. Objectives In this paper, we propose a methodology to model healthcare processes in order to break out complexity and provide transparency. Methods The model is grounded on a set of requirements that make the healthcare domain unique with respect to other knowledge domains. The modeling methodology is based on three main phases: the study of the environmental context, the conceptual modeling, and the logical modeling. Results The proposed methodology was validated by applying it to the case study of the rehabilitation process of stroke patients in the specific setting of a specialized rehabilitation center. The resulting model was used to define the specifications of a software artifact for the digital administration and collection of assessment tests that was also implemented. Conclusions Despite being only an example, our case study showed the ability of process modeling to answer the actual needs in healthcare practices. Independently from the medical domain in which the modeling effort is done, the proposed methodology is useful to create high-quality models, and to detect and take into account relevant and tricky situations that can occur during process execution. PMID:27081415

  8. Systematic review of communication partner training in aphasia: methodological quality.

    PubMed

    Cherney, Leora R; Simmons-Mackie, Nina; Raymer, Anastasia; Armstrong, Elizabeth; Holland, Audrey

    2013-10-01

    Twenty-three studies identified from a previous systematic review examining the effects of communication partner training on persons with aphasia and their communication partners were evaluated for methodological quality. Two reviewers rated the studies on defined methodological quality criteria relevant to each study design. There were 11 group studies, seven single-subject participant design studies, and five qualitative studies. Quality scores were derived for each study. The mean inter-rater reliability of scores for each study design ranged from 85-93%, with Cohen's Kappa indicating substantial agreement between raters. Methodological quality of research on communication partner training in aphasia was highly varied. Overall, group studies employed the least rigorous methodology as compared to single subject and qualitative research. Only two of 11 group studies complied with more than half of the quality criteria. No group studies reported therapist blinding and only one group study reported participant blinding. Across all types of studies, the criterion of treatment fidelity was most commonly omitted. Failure to explicitly report certain methodological quality criteria may account for low ratings. Using methodological rating scales specific to the type of study design may help improve the methodological quality of aphasia treatment studies, including those on communication partner training.

  9. Enantioselective construction of C-chiral allylic sulfilimines via the iridium-catalyzed allylic amination with S,S-diphenylsulfilimine: asymmetric synthesis of primary allylic amines† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc01317d Click here for additional data file.

    PubMed Central

    Grange, Rebecca L.; Clizbe, Elizabeth A.; Counsell, Emma J.

    2015-01-01

    We have devised a highly regio- and enantioselective iridium-catalyzed allylic amination reaction with the sulfur-stabilized aza-ylide, S,S-diphenylsulfilimine. This process provides a robust and scalable method for the construction of aryl-, alkyl- and alkenyl-substituted C-chiral allylic sulfilimines, which are important functional groups for organic synthesis. Additionally, the combination of the allylic amination with an in situ deprotection of the sulfilimine constitutes a convenient one-pot protocol for the construction of chiral nonracemic primary allylic amines. PMID:28936319

  10. Enantioselective Synthesis of α-Mercapto-β-amino Esters via Rh(II)/Chiral Phosphoric Acid-Cocatalyzed Three-Component Reaction of Diazo Compounds, Thiols, and Imines.

    PubMed

    Xiao, Guolan; Ma, Chaoqun; Xing, Dong; Hu, Wenhao

    2016-12-02

    An enantioselective method for the synthesis of α-mercapto-β-amino esters has been developed via a rhodium(II)/chiral phosphoric acid-cocatalyzed three-component reaction of diazo compounds, thiols, and imines. This transformation is proposed to proceed through enantioselective trapping of the sulfonium ylide intermediate generated in situ from the diazo compound and thiol by the phosphoric acid-activated imine. With this method, a series of α-mercapto-β-amino esters were obtained in good yields with moderate to good stereoselectivities.

  11. Straightforward Entry toward Highly Substituted 2,3-Dihydrobenz[ b]oxepines by Ring Expansion of Benzopyryliums with Donor-Acceptor Diazo Compounds.

    PubMed

    Courant, Thibaut; Pasco, Morgane; Lecourt, Thomas

    2018-05-04

    Ylide-type reactivity of diazo compounds is exploited in a new way to prepare benzo[ b]oxepines thanks to the formation of three chemical bonds and two contiguous and highly substituted stereocenters in a single pot. This cationic reaction cascade first involves addition of a donor-acceptor-substituted diazo compound to a benzopyrylium. Selective 1,2 migration of the endocyclic C-C bond then results in a ring-expansion and generates a second oxocarbenium that is trapped by a nucleophile added sequentially.

  12. The integrative review: updated methodology.

    PubMed

    Whittemore, Robin; Knafl, Kathleen

    2005-12-01

    The aim of this paper is to distinguish the integrative review method from other review methods and to propose methodological strategies specific to the integrative review method to enhance the rigour of the process. Recent evidence-based practice initiatives have increased the need for and the production of all types of reviews of the literature (integrative reviews, systematic reviews, meta-analyses, and qualitative reviews). The integrative review method is the only approach that allows for the combination of diverse methodologies (for example, experimental and non-experimental research), and has the potential to play a greater role in evidence-based practice for nursing. With respect to the integrative review method, strategies to enhance data collection and extraction have been developed; however, methods of analysis, synthesis, and conclusion drawing remain poorly formulated. A modified framework for research reviews is presented to address issues specific to the integrative review method. Issues related to specifying the review purpose, searching the literature, evaluating data from primary sources, analysing data, and presenting the results are discussed. Data analysis methods of qualitative research are proposed as strategies that enhance the rigour of combining diverse methodologies as well as empirical and theoretical sources in an integrative review. An updated integrative review method has the potential to allow for diverse primary research methods to become a greater part of evidence-based practice initiatives.

  13. Methodological pluralism in the teaching of Astronomy

    NASA Astrophysics Data System (ADS)

    de Macedo, Josué Antunes; Voelzke, Marcos Rincon

    2015-04-01

    This paper discusses the feasibility of using a teaching strategy called methodological pluralism, consisting of the use of various methodological resources in order to provide a meaningful learning. It is part of a doctoral thesis, which aims to investigate contributions to the use of traditional resources combined with digital technologies, in order to create autonomy for future teachers of Natural Sciences and Mathematics in relation to themes in Astronomy. It was offered an extension course at the "Federal Institution of Education, Science and Technology" in the North of Minas Gerais (FINMG), Campus Januaria, for thirty-two students of licentiate courses in Physics, Mathematics and Biological Sciences, involving themes of Astronomy, in order to search and contribute to improving the training of future teachers. The following aspects are used: the mixed methodology, with pre-experimental design, combined with content analysis. The results indicate the rates of students' prior knowledge in relation to Astronomy was low; meaningful learning indications of concepts related to Astronomy, and the feasibility of using digital resources Involving technologies, articulated with traditional materials in the teaching of Astronomy. This research sought to contribute to the initial teacher training, especially in relation to Astronomy Teaching, proposing new alternatives to promote the teaching of this area of knowledge, extending the methodological options of future teachers.

  14. Methodological Problems of Soviet Pedagogy

    ERIC Educational Resources Information Center

    Noah, Harold J., Ed.; Beach, Beatrice S., Ed.

    1974-01-01

    Selected papers presented at the First Scientific Conference of Pedagogical Scholars of Socialist Countries, Moscow, 1971, deal with methodology in relation to science, human development, sociology, psychology, cybernetics, and the learning process. (KM)

  15. Using a Realist Research Methodology in Policy Analysis

    ERIC Educational Resources Information Center

    Lourie, Megan; Rata, Elizabeth

    2017-01-01

    The article describes the usefulness of a realist methodology in linking sociological theory to empirically obtained data through the development of a methodological device. Three layers of analysis were integrated: 1. the findings from a case study about Maori language education in New Zealand; 2. the identification and analysis of contradictions…

  16. Representation of Scientific Methodology in Secondary Science Textbooks

    ERIC Educational Resources Information Center

    Binns, Ian C.

    2009-01-01

    The purpose of this investigation was to assess the representation of scientific methodology in secondary science textbooks. More specifically, this study looked at how textbooks introduced scientific methodology and to what degree the examples from the rest of the textbook, the investigations, and the images were consistent with the text's…

  17. Health economic assessment: a methodological primer.

    PubMed

    Simoens, Steven

    2009-12-01

    This review article aims to provide an introduction to the methodology of health economic assessment of a health technology. Attention is paid to defining the fundamental concepts and terms that are relevant to health economic assessments. The article describes the methodology underlying a cost study (identification, measurement and valuation of resource use, calculation of costs), an economic evaluation (type of economic evaluation, the cost-effectiveness plane, trial- and model-based economic evaluation, discounting, sensitivity analysis, incremental analysis), and a budget impact analysis. Key references are provided for those readers who wish a more advanced understanding of health economic assessments.

  18. Health Economic Assessment: A Methodological Primer

    PubMed Central

    Simoens, Steven

    2009-01-01

    This review article aims to provide an introduction to the methodology of health economic assessment of a health technology. Attention is paid to defining the fundamental concepts and terms that are relevant to health economic assessments. The article describes the methodology underlying a cost study (identification, measurement and valuation of resource use, calculation of costs), an economic evaluation (type of economic evaluation, the cost-effectiveness plane, trial- and model-based economic evaluation, discounting, sensitivity analysis, incremental analysis), and a budget impact analysis. Key references are provided for those readers who wish a more advanced understanding of health economic assessments. PMID:20049237

  19. Space Engineering Projects in Design Methodology

    NASA Technical Reports Server (NTRS)

    Crawford, R.; Wood, K.; Nichols, S.; Hearn, C.; Corrier, S.; DeKunder, G.; George, S.; Hysinger, C.; Johnson, C.; Kubasta, K.

    1993-01-01

    NASA/USRA is an ongoing sponsor of space design projects in the senior design courses of the Mechanical Engineering Department at The University of Texas at Austin. This paper describes the UT senior design sequence, focusing on the first-semester design methodology course. The philosophical basis and pedagogical structure of this course is summarized. A history of the Department's activities in the Advanced Design Program is then presented. The paper includes a summary of the projects completed during the 1992-93 Academic Year in the methodology course, and concludes with an example of two projects completed by student design teams.

  20. The retrospective chart review: important methodological considerations.

    PubMed

    Vassar, Matt; Holzmann, Matthew

    2013-01-01

    In this paper, we review and discuss ten common methodological mistakes found in retrospective chart reviews. The retrospective chart review is a widely applicable research methodology that can be used by healthcare disciplines as a means to direct subsequent prospective investigations. In many cases in this review, we have also provided suggestions or accessible resources that researchers can apply as a "best practices" guide when planning, conducting, or reviewing this investigative method.

  1. Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors.

    PubMed

    Kia, Yalda; Osman, Hasnah; Suresh Kumar, Raju; Basiri, Alireza; Murugaiyah, Vikneswaran

    2014-04-01

    Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 μM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 μM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Transportation technology and methodology reports

    DOT National Transportation Integrated Search

    1999-12-22

    This Internet site sponsored by the Office of Highway Policy Information provides links to a compilation of PDF reports on transportation technology and methodology. Reports include "FHWA Statistical Programs;" "Nonresponse in Household Travel Survey...

  3. The 'Direct Attack' Strategy for Poverty Removal: Implementation Methodology.

    ERIC Educational Resources Information Center

    Sinha, Sanjay

    1981-01-01

    Discusses elements of an implementation methodology for the removal of poverty in India. Includes background, methodology, aggregation of demands, economics of the strategy, complementary activities and infrastructure, mechanics of implementation, and monitoring. (CT)

  4. Applications of mixed-methods methodology in clinical pharmacy research.

    PubMed

    Hadi, Muhammad Abdul; Closs, S José

    2016-06-01

    Introduction Mixed-methods methodology, as the name suggests refers to mixing of elements of both qualitative and quantitative methodologies in a single study. In the past decade, mixed-methods methodology has gained popularity among healthcare researchers as it promises to bring together the strengths of both qualitative and quantitative approaches. Methodology A number of mixed-methods designs are available in the literature and the four most commonly used designs in healthcare research are: the convergent parallel design, the embedded design, the exploratory design, and the explanatory design. Each has its own unique advantages, challenges and procedures and selection of a particular design should be guided by the research question. Guidance on designing, conducting and reporting mixed-methods research is available in the literature, so it is advisable to adhere to this to ensure methodological rigour. When to use it is best suited when the research questions require: triangulating findings from different methodologies to explain a single phenomenon; clarifying the results of one method using another method; informing the design of one method based on the findings of another method, development of a scale/questionnaire and answering different research questions within a single study. Two case studies have been presented to illustrate possible applications of mixed-methods methodology. Limitations Possessing the necessary knowledge and skills to undertake qualitative and quantitative data collection, analysis, interpretation and integration remains the biggest challenge for researchers conducting mixed-methods studies. Sequential study designs are often time consuming, being in two (or more) phases whereas concurrent study designs may require more than one data collector to collect both qualitative and quantitative data at the same time.

  5. A Triazole-Containing Metal-Organic Framework as a Highly Effective and Substrate Size-Dependent Catalyst for CO2 Conversion.

    PubMed

    Li, Pei-Zhou; Wang, Xiao-Jun; Liu, Jia; Lim, Jie Sheng; Zou, Ruqiang; Zhao, Yanli

    2016-02-24

    A highly porous metal-organic framework (MOF) incorporating both exposed metal sites and nitrogen-rich triazole groups was successfully constructed via solvothermal assembly of a clicked octcarboxylate ligand and Cu(II) ions, which presents a high affinity toward CO2 molecules clearly verified by gas adsorption and Raman spectral detection. The constructed MOF featuring CO2-adsorbing property and exposed Lewis-acid metal sites could serve as an excellent catalyst for CO2-based chemical fixation. Catalytic activity of the MOF was confirmed by remarkably high efficiency on CO2 cycloaddition with small epoxides. When extending the substrates to larger ones, its activity showed a sharp decrease. These observations reveal that MOF-catalyzed CO2 cycloaddition of small substrates was carried out within the framework, while large ones cannot easily enter into the porous framework for catalytic reactions. Thus, the synthesized MOF exhibits high catalytic selectivity to different substrates on account of the confinement of the pore diameter. The high efficiency and size-dependent selectivity toward small epoxides on catalytic CO2 cycloaddition make this MOF a promising heterogeneous catalyst for carbon fixation.

  6. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  7. [Methodology of psychiatric case histories].

    PubMed

    Scherbaum, N; Mirzaian, E

    1999-05-01

    This paper deals with the methodology of psychiatric case histories. Three types of case histories are differentiated. The didactic case history teaches about the typical aspects of a psychiatric disorder or treatment by using an individual patient as an example. In the heuristic case history the individual case gives rise to challenging established concepts or to generate new hypotheses. Such hypotheses drawn from inductive reasoning have then to be tested using representative samples. The focus of hermeneutic case histories is the significance of pathological behaviour and experience in the context of the biography of an individual patient. So-called psychopathographies of important historical figures can also be differentiated according to these types. Based on these methodological considerations, quality standards for the named types of case histories are stated.

  8. Design methodology of Dutch banknotes

    NASA Astrophysics Data System (ADS)

    de Heij, Hans A. M.

    2000-04-01

    Since the introduction of a design methodology for Dutch banknotes, the quality of Dutch paper currency has improved in more than one way. The methodology is question provides for (i) a design policy, which helps fix clear objectives; (ii) design management, to ensure a smooth cooperation between the graphic designer, printer, papermaker an central bank, (iii) a program of requirements, a banknote development guideline for all parties involved. This systematic approach enables an objective selection of design proposals, including security features. Furthermore, the project manager obtains regular feedback from the public by conducting market surveys. Each new design of a Netherlands Guilder banknote issued by the Nederlandsche Bank of the past 50 years has been an improvement on its predecessor in terms of value recognition, security and durability.

  9. A Call for a New National Norming Methodology.

    ERIC Educational Resources Information Center

    Ligon, Glynn; Mangino, Evangelina

    Issues related to achieving adequate national norms are reviewed, and a new methodology is proposed that would work to provide a true measure of national achievement levels on an annual basis and would enable reporting results in current-year norms. Statistical methodology and technology could combine to create a national norming process that…

  10. Political Transformation and Research Methodology in Doctoral Education

    ERIC Educational Resources Information Center

    Herman, Chaya

    2010-01-01

    This paper examines the relationship between political change and epistemologies and methodologies employed at doctorate level. It does so by analysing the range of topics, questions and methodologies used by doctoral students at the University of Pretoria's Faculty of Education between 1985 and 2005--a time-frame that covers the decade before and…

  11. Methodological Advances in the Study of Self-Concept.

    ERIC Educational Resources Information Center

    Schwartz, Terrence J.

    Critical review of previous techniques for the measurement of an individual's self-concept (SC) is a necessary prelude to the development of more adequate methodologies. This paper focuses on recent methodological innovations in the study of the self, namely, those derived from cognitive social psychology. A view of the self as a cognitive…

  12. Tire pressure special study : methodology

    DOT National Transportation Integrated Search

    2001-08-01

    Tire Pressure Special Study: Methodology is the : first in a series of research notes pertaining to the : Tire Pressure Special Study (TPSS) conducted by : the National Highway Traffic Safety Administration : (NHTSA). Upcoming research notes wi...

  13. Observations of fallibility in applications of modern programming methodologies

    NASA Technical Reports Server (NTRS)

    Gerhart, S. L.; Yelowitz, L.

    1976-01-01

    Errors, inconsistencies, or confusing points are noted in a variety of published algorithms, many of which are being used as examples in formulating or teaching principles of such modern programming methodologies as formal specification, systematic construction, and correctness proving. Common properties of these points of contention are abstracted. These properties are then used to pinpoint possible causes of the errors and to formulate general guidelines which might help to avoid further errors. The common characteristic of mathematical rigor and reasoning in these examples is noted, leading to some discussion about fallibility in mathematics, and its relationship to fallibility in these programming methodologies. The overriding goal is to cast a more realistic perspective on the methodologies, particularly with respect to older methodologies, such as testing, and to provide constructive recommendations for their improvement.

  14. Field Test of the Methodology for Succession Planning for Technical Experts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cain, Ronald A.; Kirk, Bernadette Lugue; Agreda, Carla L.

    This report complements A Methodology for Succession Planning for Technical Experts (Ron Cain, Shaheen Dewji, Carla Agreda, Bernadette Kirk, July 2017), which describes a methodology for identifying and evaluating the loss of key technical skills at nuclear operations facilities. This report targets the methodology for identifying critical skills, hereafter referred to as “core competencies”. The methodology has been field tested by interviewing selected retiring subject matter experts (SMEs).

  15. Exploring Alternative Approaches to Methodology in Educational Research

    ERIC Educational Resources Information Center

    Niaz, Mansoor

    2004-01-01

    The objective of this study is to provide in-service teachers an opportunity to become familiar with the controversial nature of progress in science (growth of knowledge) and its implications for research methodology in education. The study is based on 41 participants who had registered for a nine-week course on Methodology of Investigation in…

  16. Methodological quality of meta-analyses of single-case experimental studies.

    PubMed

    Jamshidi, Laleh; Heyvaert, Mieke; Declercq, Lies; Fernández-Castilla, Belén; Ferron, John M; Moeyaert, Mariola; Beretvas, S Natasha; Onghena, Patrick; Van den Noortgate, Wim

    2017-12-28

    Methodological rigor is a fundamental factor in the validity and credibility of the results of a meta-analysis. Following an increasing interest in single-case experimental design (SCED) meta-analyses, the current study investigates the methodological quality of SCED meta-analyses. We assessed the methodological quality of 178 SCED meta-analyses published between 1985 and 2015 through the modified Revised-Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. The main finding of the current review is that the methodological quality of the SCED meta-analyses has increased over time, but is still low according to the R-AMSTAR checklist. A remarkable percentage of the studies (93.80% of the included SCED meta-analyses) did not even reach the midpoint score (22, on a scale of 0-44). The mean and median methodological quality scores were 15.57 and 16, respectively. Relatively high scores were observed for "providing the characteristics of the included studies" and "doing comprehensive literature search". The key areas of deficiency were "reporting an assessment of the likelihood of publication bias" and "using the methods appropriately to combine the findings of studies". Although the results of the current review reveal that the methodological quality of the SCED meta-analyses has increased over time, still more efforts are needed to improve their methodological quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Guidelines for reporting evaluations based on observational methodology.

    PubMed

    Portell, Mariona; Anguera, M Teresa; Chacón-Moscoso, Salvador; Sanduvete-Chaves, Susana

    2015-01-01

    Observational methodology is one of the most suitable research designs for evaluating fidelity of implementation, especially in complex interventions. However, the conduct and reporting of observational studies is hampered by the absence of specific guidelines, such as those that exist for other evaluation designs. This lack of specific guidance poses a threat to the quality and transparency of these studies and also constitutes a considerable publication hurdle. The aim of this study thus was to draw up a set of proposed guidelines for reporting evaluations based on observational methodology. The guidelines were developed by triangulating three sources of information: observational studies performed in different fields by experts in observational methodology, reporting guidelines for general studies and studies with similar designs to observational studies, and proposals from experts in observational methodology at scientific meetings. We produced a list of guidelines grouped into three domains: intervention and expected outcomes, methods, and results. The result is a useful, carefully crafted set of simple guidelines for conducting and reporting observational studies in the field of program evaluation.

  18. Some Findings Concerning Requirements in Agile Methodologies

    NASA Astrophysics Data System (ADS)

    Rodríguez, Pilar; Yagüe, Agustín; Alarcón, Pedro P.; Garbajosa, Juan

    Agile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies.

  19. Methodology for Designing Fault-Protection Software

    NASA Technical Reports Server (NTRS)

    Barltrop, Kevin; Levison, Jeffrey; Kan, Edwin

    2006-01-01

    A document describes a methodology for designing fault-protection (FP) software for autonomous spacecraft. The methodology embodies and extends established engineering practices in the technical discipline of Fault Detection, Diagnosis, Mitigation, and Recovery; and has been successfully implemented in the Deep Impact Spacecraft, a NASA Discovery mission. Based on established concepts of Fault Monitors and Responses, this FP methodology extends the notion of Opinion, Symptom, Alarm (aka Fault), and Response with numerous new notions, sub-notions, software constructs, and logic and timing gates. For example, Monitor generates a RawOpinion, which graduates into Opinion, categorized into no-opinion, acceptable, or unacceptable opinion. RaiseSymptom, ForceSymptom, and ClearSymptom govern the establishment and then mapping to an Alarm (aka Fault). Local Response is distinguished from FP System Response. A 1-to-n and n-to- 1 mapping is established among Monitors, Symptoms, and Responses. Responses are categorized by device versus by function. Responses operate in tiers, where the early tiers attempt to resolve the Fault in a localized step-by-step fashion, relegating more system-level response to later tier(s). Recovery actions are gated by epoch recovery timing, enabling strategy, urgency, MaxRetry gate, hardware availability, hazardous versus ordinary fault, and many other priority gates. This methodology is systematic, logical, and uses multiple linked tables, parameter files, and recovery command sequences. The credibility of the FP design is proven via a fault-tree analysis "top-down" approach, and a functional fault-mode-effects-and-analysis via "bottoms-up" approach. Via this process, the mitigation and recovery strategy(s) per Fault Containment Region scope (width versus depth) the FP architecture.

  20. A Hierarchical Clustering Methodology for the Estimation of Toxicity

    EPA Science Inventory

    A Quantitative Structure Activity Relationship (QSAR) methodology based on hierarchical clustering was developed to predict toxicological endpoints. This methodology utilizes Ward's method to divide a training set into a series of structurally similar clusters. The structural sim...