Recent work has shown that sulfones are unique synthetic tools capable of undergoing numerous transformations and reactions. The sulfone group is a strong electron withdrawing group and has the ability to stabilize an α-sulfonyl carbanion. As such, unsaturated sulfones can undergo a variety of reactions, i.e. conjugate additions, alkylation etc. Beside this, α sulfonyl carbanion can be generated with strong base and α sulfonyl carbanion can also be used in various reactions. This report is an investigation of a novel base induced cyclization of various alkynyl sulfones. The results revealed that the reaction does not significantly depend on the electronic effects of substituents in the aromatic ring. Additional versatility in this process was demonstrated with respect to a diverse array of functionality at various positions i.e. benzylic position, aromatic ring and terminal position of alkyne. These alkynyl sulfones, bearing a larger group at ortho position and any group at benzylic position underwent intramolecular cyclization when treated with base affording benzothiopyran S,S-dioxide. The results demonstrated that the cyclization efficiency was significantly influenced by the steric effects of substituents of aromatic ring at ortho positions and blocking the terminal position with phenyl since the cyclization reaction gave low or no yields with aromatic rings having a substituent at para, meta or to position than those having no substituent. It was also found that 2-thiophenylmethyl sulfones cyclize more efficiently than benzyl and furfuryl sulfones. The evidence from mechanistic studies points to a mechanism for the cyclization that involves disruption of aromaticity. To disrupt aromaticity, a deprotonation at benzylic position is a requirement for this cyclization reaction. Results suggest that the cyclization also requires an available hydrogen at the point where the potential ring would be fused. Several intermediates were also observed spectroscopically and identified by ReactIR®.

Transition-metal-catalyzed asymmetric hydrogenation is one of the most efficient, straightforward, and well-established methods for preparing enantiomerically enriched compounds. Over the past decades, significant progress has been made with iridium, rhodium and ruthenium complexes to asymmetric hydrogenate a selection of olefins, such as, α,β-unsaturated carboxylic acid derivatives, ketones, imines and phosphonates. Although these metals have been applied successfully in the hydrogenation of olefins, they differ in their substrate tolerance.  Ruthenium and rhodium based catalysts require a coordinating group in the vicinity of the C=C bond. However, iridium based catalysts do not require this coordinating group, hence, asymmetric hydrogenation with iridium catalysts has been widely used for both functionalized and unfunctionalized olefin substrates. This thesis focuses on expanding the substrate scope for asymmetric hydrogenation using chiral N,P-ligated iridium catalysts. Papers I and II investigate the asymmetric hydrogenation of prochiral N-heterocyclic compounds prepared by ring-closing metathesis using the iridium catalysts developed in our group.  These substrates are interesting as they bear resemblance to pharmaceutically active compounds and therefore have tremendous value in medicinal chemistry.  Excellent enantioselectivities, up to >99% ee and conversions were obtained. In papers III and IV we synthesized many unsaturated acyclic and cyclic sulfones with varying substitution patterns.  The sulfones were subjected to hydrogenation using our N,P-ligated iridium catalysts, producing the chiral sulfone products in high enantiomeric excess (up to 99% ee). This methodology was combined with the Ramberg-Bäcklund reaction, offering a novel route to chiral allylic and homoallylic compounds. In addition to obtaining these chiral compounds in good yields, no decrease in enantiomeric excess was observed after the Ramberg-Bäcklund reaction. This strategy has been applied in the preparation of the chiral building block for renin inhibitors.

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High temperature, solvent resistant materials which also display good mechanical properties are desired for use as aerospace structural adhesives and polymer matrix/carbon fiber composites. High molecular weight amorphous poly(arylene ether sulfone) thermoplastic materials display many of these desirable characteristics but are deficient in solvent resistance. Previous attempts to prepare poly(arylene ether) based thermosets to improve solvent resistance have been largely unsuccessful due to processiblity issues from the low curing temperature and high glass transition temperature of the thermoset precursor. Incorporation of a high temperature curable (* 350°C) endgroup such as 3-phenylethynylphenol in the synthesis of controlled molecular weight poly(arylene ether sulfone) oligomers has allowed for a large processing window prior to the exothermic cure that forms the desired networks. Control of oligomer molecular weight and backbone structure has allowed for further control of the processing, thermal transitions and adhesive properties of the thermosets. A systematic series of phenylethynyl terminated oligomers derived from either bisphenol A, or wholly aromatic hydroquinone or biphenol has been synthesized and characterized to determine the influence of backbone structure, molecular weight, and endgroup structure on thermoset properties. The features most affected by backbone structure included thermal stability (weight loss behavior) as well as transition temperatures (Tg, Tm), and processing characteristics. Increasing molecular weight of the oligomer produced a decrease in the glass transition temperature of the network and an increase in the adhesive properties of the thermoset. Comparison of the curing behavior of the 3-phenylethynylphenol endcapped materials with other related phenylethynyl terminated compounds led to the synthesis and systematic investigation of the curing behavior of phenylethynyl endcappers in which the electronic environment in relation to the reactive ethynyl carbons was systematically varied. Electron withdrawing groups, eg. sulfone, ketone, imide on the aryl ring para to the acetylene bond enhanced the rate of cure and also appear to improve the lap shear adhesion to suface treated titanium adherands. Discussion of the background, synthesis and characterization are described in this dissertation. / Ph. D.

Les spirocétals sont des sous-unités présentes dans de nombreuses molécules naturelles d’intérêt biologique. Pour accéder à ces structures, la spirocyclisation d’éthers d’énol en milieu acide est une méthode de choix. L’application de la réaction de Julia-Kocienski à des lactones a permis d’obtenir exo-glycals et éthers d’énol exo-cycliques tri- et tétrasubstitués. Selon l’hétérocycle porté parla sulfone engagée, l’un ou l’autre des diastéréoisomères de l’éther d’énol peut être obtenu préférentiellement. La spirocyclisation des produits formés, si elle est réalisée dans des conditions thermodynamiques, mène au [6.6]-spirocétal le plus stable. Des conditions permettant d’obtenir le diastéréoisomère cinétique ont également été étudiées. Les spirocétals ainsi préparés ont été utilisés en synthèse totale. Par exemple, le fragment spirocétal de la Broussonetine H, ainsi que l’unité iminosucre, ont été obtenus efficacement de façon énantiopure. Enfin, les spirocétals diversement substitués ont permis de préparer plusieurs analogues du Bistramide A. Ce métabolite marin est un agent anticancéreux puissant qui se lie à l’actine pour bloquer la division cellulaire mais des interactions avec PKC-TM, notamment impliquant l’apoptose, sont à l’étude / Spiroketals are often found as structural subunits of many biologically active natural compounds. One of the more powerful methods to access this structure is the acid-catalyzed cyclization of enol ethers. The reaction of Julia-Kocienski reagents with lactones allows us to synthesize various tri- and tetrasubstituted exo-glycals and exo-cyclic enol ethers. It is possible to obtain preferentially either one or the other of the two diastereoisomeric enol ethers by varrying the heterocycle moiety of the sulfone. These enol éthers are cyclized under thermodynamic conditions leading to the more stable [6.6]-spiroketal but other conditions may allow us to obtain the kineticisomer. Thermodynamic spiroketals were used in total synthesis. For example, both fragments ofBroussonetine H (one iminosugar and one spiroketal) have been readily and effectively prepared.Finally, diversely substituted spiroketals have been synthesized to prepare analogues of Bistramide A.This marine metabolite is a powerful antitumor agent that binds to actin and thus blocks cell divisionalthough some interactions involving PKC-TM are actually under study.

Les « -Izidines » sont des motifs présents dans de nombreuses alcaloïdes. Pour accéder à ces structures, la formation de la liaison C=C exendo est une méthode de choix. L’application de la réaction de Julia-Kocienski intramoléculaire sur des imides permettrait d’obtenir des enamides portant la liaison C=C exendo. Notre équipe s’est intéressée depuis 2005 à l’application de la réaction de Julia-Kocienski les lactones. Dans la continuité de travaux précédents, cette thèse décrit l’application de la réaction de Julia-Kocienski intramoléculaire pour former des enamides. Cette réaction permet d’obtenir tous les motifs « -Izidine » tels que le pyrrolidizine, l’indolizidine ou le quinolizidine. Selon les conditions réactionnelles, il est possible d’obtenir les enamides ou les vinylsulfones. Pour ces deux types de réactions, les résultats obtenus peuvent être classés en fonction des groupements présents sur les imidesL’étude mécanistique par les calculs de DFT, en collaboration avec Dr. Lionel Perrin, montre que l’effet stérique ou électronique des groupements sur les imides peut influencer les résultats de la formation des enamides ou des vinylsulfones. Afin d’illustrer la méthodologie de la réaction de Julia-Kocienski intramoléculaire sur les imides, un analogue oxo du FR901483 a été choisi comme une cible de la synthèse totale. Les réactivités différentes de celles observées dans la littérature des groupements présents sur les intermédiaires nous avons conduits à appliquer d’autres alternatives à littérature. Ce phénomène pourrait bien être lié à l’interaction entre les groupements sur une espace atomique restreint / “-Izidines” units are often found as structural subunits of many alkaloids. One of the powerful methods to access this structure is the formation of the C=C bond exendo. The application of the intramolecular Julia-Kocienski reaction on imides should allow this formation.Our group has a long-standing interest in the application of the Julia-Kocienski reaction on lactones. In line with previous efforts, the herein presented work details the syntheses of enamides via application of the intramolecular Julia-Kocienski reaction on imides. This new method enables us to obtain different “-Izidine” units such as pyrrolizidine, indolizidine, and quinolizidine. Depending on the reaction conditions, it is possible to obtain the enamide or vinylsulfones. In both reactions, the present moiety on imides can affect the outcome.Computational mechanistic study, by collaboration with Dr. Lionel Perrin, shows the steric or electronic effect of the present functional groups on imides influence the results of the formation of the enamides or vinylsulfones.Having a goal of applying this new methodology towards total synthesis of natural products, we started the synthesis of oxo-analog of FR901483. During our synthesis, a number of uncommon reactivities of the presented functional groups were observed. This phenomenon led us to applying different methods than those of the literature

L’utilisation du dioxyde de carbone (CO₂) comme source de composés C1 pour la chimie fine est intéressante d’un point de vue économique et pour des raisons écologiques. Issu de l’oxydation de la matière carbonée, le CO₂ est un gaz non-toxique, abondant et peu coûteux. Sa transformation en produits chimiques présentant de hautes valeurs ajoutées est actuellement entravée par sa stabilité thermodynamique. Afin de développer de nouveaux processus et catalyseurs pour la réduction catalytique du CO₂, une compréhension détaillée des mécanismes réactionnels de l’activation et de la réduction de ce gaz est nécessaire. En utilisant comme catalyseurs des paires de Lewis frustrée (FLPs) contenant une base azotée liée à un ion silicénium, les influences respectives de l’adduit CO₂-FLP et du réducteur ont été déterminées expérimentalement et par calcul DFT dans le cadre de l’hydroboration du CO₂ en équivalent de méthanol. Une nouvelle réaction visant à la création de liaisons carbone–carbone par le transfert du fragment pyridyle de molécules de pyridylsilanes (C₅H₄N–SiMe₃) sur le CO₂ était également étudiée. Le mécanisme réactionnel de cette transformation a été établi sur la base de calculs théoriques. Nous avons montré le double rôle du CO₂ qui est à la fois un réactif et un catalyseur de la réaction de transfert du groupe pyridyle. La compréhension fine de cette réaction nous a permis de l’étendre à la formation de sulfones et sulfonamides qui sont des groupements chimiques essentiels dans le domaine pharmaceutique. En utilisant le SO₂ à la fois comme catalyseur et réactif, des silanes aromatiques et hétéro-aromatiques ont été transformés en sulfones correspondants en une seule étape. Finalement, nous avons trouvé un couplage croisé original, de type Hiyama, entre espèces aromatiques électrophiles et des espèces C(sp2)–Si nucléophiles en présence de SO₂. / The use of CO₂ as a C1 chemical feedstock for the fine chemical industry is interesting both economically and ecologically, as CO₂ is non-toxic, abundant and cheap. Nevertheless, transformations of CO₂ into value-added products is hampered by its high thermodynamic stability and its inertness toward reduction. In order to design new catalysts able to overcome this kinetic challenge, a profound understanding of the reaction mechanisms at play in CO₂ reduction is needed. Using novel N/Si+ frustrated Lewis pairs (FLPs), the influence of CO₂ adducts and different hydroborane reducing agents on the reaction mechanism in the catalytic hydroboration of CO₂ were investigated, both by DFT calculations and experiments. In a second step, the reaction mechanism of a novel reaction for the creation of C–C bonds from CO₂ and pyridylsilanes (C₅H₄N–SiMe₃) was analyzed by DFT calculations. It was shown that CO₂ plays a double role in this transformation, acting both as a catalyst and a C1-building block. The fine understanding of this transformation then led to the development of a novel approach for the synthesis of sulfones and sulfonamides. Starting from SO₂ and aromatic silanes/amine silanes, these products were obtained in a single step under metal-free conditions. Noteworthy, sulfones and sulfonamides are common motifs in organic chemistry and found in a variety of highly important drugs. Finally, this concept was extended to aromatic halides as coupling partners, and it was thus shown for the first time that a sulfonylative Hiyama reaction is a possible approach to the synthesis of sulfones.

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The results described in this dissertation have demonstrated several alternative proton exchange membranes (PEM) for hydrogen-air and direct methanol fuel cells (DMFC) that perform as well or better than the state of the art Nafion perfluorosulfonic acid membrane. Direct aromatic nucleophilic substitution polycondensations of disodium 3,3′ S-disulfonate-4,4′ S-difluorodiphenylsulfone (SDFDPS), 4,4′ S-difluorodiphenylsulfone (DFDPS) (or their chlorinated analogs, SDCDPS, DCDPS) and 4,4′ S-thiobisbenzenethiol (TBBT) in the presence of potassium carbonate were investigated. Electrophilic aromatic substitution was employed to synthesize the SDFDPS or SDCDPS comonomers in high yields and purity. High molecular weight disulfonated poly(arylene thioether sulfone) (PATS) copolymers were easily obtained using the SDFDPS monomers, but in general, slower rates and a lower molecular weight copolymer was obtained using the analogous chlorinated monomers. Tough and ductile membranes were solution cast from N,N-dimethylacetamide for both series of copolymers. The degrees of disulfonation (20-50%, PATS 20-50) were controlled by varying the ratio of disulfonated to unsulfonated comonomers. Composite membranes were prepared by homogeneous solution blending the copolymers with phosphotungstic acid (PTA) in dimethylacetamide (DMAc). The composite PATS membranes exhibited moderate PTA molecule water extraction after acidification treatments performed at either room or boiling temperatures. The membranes containing HPA showed improved conductivity at high temperatures (120 °C) and low relative humidities when compared to the pure copolymers. Molecular weight of the copolymers plays a critical role in the overall copolymer physical behavior. It is well known that molecular weight has an enormous impact on practically all of the physical properties of polymeric systems. This dissertation discusses the influence of molecular weight on the characteristics of a specific family of PEM PATS copolymers. This study elucidated that the lower molecular weight materials did indeed behave differently than the higher molecular weight copolymers. Specifically, the water uptake and permeability to methanol decreased with increasing molecular weight. Furthermore, the fully hydrated mechanical properties also improved with molecular weight. The synthesis and fabrication of 45 mole percent disulfonated poly(arylene ether phenyl phosphine oxide diphenyl sulfone) terpolymer-heteropolyacid (HPA) composite membranes and membrane electrode assemblies were chosen for detailed investigation. A series of 45 mole percent disulfonated biphenol-based poly(arylene ether phenyl phosphine oxide diphenyl sulfone) terpolymers (BPSH45-PPO) were also synthesized by nucleophilic aromatic substitution polymerizations. The level of disulfonation was constant at 45 mole percent providing a compromise between high conductivity at low humidity and reasonable mechanical properties in liquid water. The amounts of 4,4′-difluorodiphenyl phenyl phosphine oxide comonomer incorporated into the terpolymer backbone were precisely controlled from 0-50 mole percent relative to the 4,4′-dihalodiphenyl sulfone. Phosphine oxide moieties were employed to enhance the interactions with the PTA relative to the pure copolymer. The composite BPSH45-PPO membranes exhibited lower HPA molecule water extraction after acidification at room and boiling temperatures, which was ascribed to the strong hydrogen and polar interactions between the phosphine oxide moiety and functional groups on the HPA. The membranes containing HPA displayed improved conductivity at high temperatures and low relative humidities when compared to the pure terpolymer samples. The increase of proton conductivity was attributed to the water retention characteristics of the HPA molecules, which allowed enhanced mobility of the protons even at lower humidification levels, providing superior hydrogen-air fuel cell performance. The effect of hexafluoroisopropylidene bisphenol (6FBP) incorporation into 45 mole percent disulfonated poly(arylene ether sulfone) copolymers was investigated. This novel series of directly disulfonated poly(arylene ether sulfone) copolymers with various mole ratios of the 6FBP were synthesized in high molecular weight. The levels of fluorination within the statistically random copolymer architecture were varied from 0-100 mole percent using 6FBP and the correct stoichiometric amount of 4,4′-biphenol. The 6FBP monomer was introduced to decrease the water swelling and improve bonding characteristics with Nafion-bonded electrodes. Indeed, water uptake decreased with increasing incorporation of the 6FBP monomer into the terpolymer. This suggested that the hydrophobic fluorinated material aided in water repulsion of the system. Proton conductivity decreased slightly as the amount of fluorination increased, which was interpreted to be due to the decrease in the ion-exchange capacity. High temperature hydrogen/air fuel cell experiments indicated better Nafion-bonded electrode adhesion for the partially fluorinated materials, as depicted by high temperature (120 °C) and low humidity (50% RH) hydrogen-air fuel cell performance. Investigations into polymeric electromechanical transducers were based on poly(arylene sulfone) ion-exchange membranes bonded between two conductive metal layer electrodes. Imposed deformations and small electric fields allowed similar explorations of both sensing and actuation applications. These copolymers produced larger sensitivities than the benchmark Nafion systems, which was interpreted as being due to their higher hydrated moduli. Methodologies for better defining the morphology of the electrodes were identified to enhance the capacitance and effective interfacial area of the conductive electrodes. The new procedures afforded major improvements to performance and transduction. Transducer actuation at lower frequencies was improved by employing a new direct assembly electrode fabrication technique that suggested a strong correlation between the capacitance and charge motion. / Ph. D.