The development of the interrupted Nazarov cyclization of allenyl vinyl ketones is presented. The intermediate oxyallyl cation, derived from an allenyl vinyl ketone, may be trapped efficiently by a divergent array of nucleophilic species generating functionalized cyclopent-2-enone products. Allenyl vinyl ketones are also a versatile source of cyclic molecules via a tandem reaction sequence terminated via reaction with acyclic dienes, cyclic dienes, aza-heterocycles, electron-rich alkenes, or styrenes by the formation of an additional ring by a [4 + 3] and/or [3 + 2] cyclization or by the formation of one additional carbon-carbon bond. The bicyclic compounds generated by these processes are densely substituted, and would be difficult to access as succinctly in other ways. The products of these interrupted Nazarov reactions generally reflect excellent regio- and stereoselectivity in the trapping reaction. In some instances, equilibrating conditions were shown to enhance the proportion of one product at the expense of another or to provide a different carbon skeleton. This process appears fairly general, and can be conducted with unsubstituted or alkyl, aromatic, or heteroaromatic allenyl vinyl ketones. The exceptional affinity of allenyl vinyl ketones to undergo interrupted Nazarov reactions is likely a result of the increased longevity of the intermediate oxyallyl cation, due in part to the increased resonance stabilization provided by the allene unit. The high regioselectivity noted in the trapping process was computationally and experimentally confirmed to be a result of a localization of the positive charge in the intermediate oxyallyl cation. The application of this recently developed methodology towards the synthesis of the natural product (+)-roseadione is also described. The tandem Nazarov/[4 + 3] cascade of allenyl vinyl ketones provides a unique manner in which to access the tricyclic core of this cyclooctanoid natural product, a molecule which, to date, has never been synthesized.

Carbo- and heterocyclic compounds are of great interest to chemists. Intramolecular cyclization strategies of donor-acceptor (D-A) cyclopropanes and alkylidene malonate monoamides have excellent potential for synthesis as they offer easy access to structurally-diverse compounds. The work described in this thesis accesses the scope of the In(OTf)3-catalyzed cyclization reaction of cyclopropanes and alkylidene malonate monoamides. In(OTf)3-catalyzed reactions of alkenyl and heteroaryl cyclopropyl ketones were examined in the synthesis of functionalized cyclohexenone-based derivatives (Chapter 2). Subsequent efforts to utilize a tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence of methyl 1-(1H-indolecarbonyl)-1-cyclopropanecarboxylates to prepare functionalized hydropyrido[1,2-a]indole-6(7H)-ones is discussed in Chapter 3. The extension of this tandem protocol towards the total synthesis of (±)-deethyleburnamonine is the subject of Chapter 6. Intramolecular Friedel-Crafts alkylation of N-indolyl alkylidene malonate monoamides was also examined. An In(OTf)3-catalyzed cyclization of substituted methyl 2-(1H-indole-1-carbonyl) acrylates afforded a series of 1H-pyrrolo[1,2-a]indole-3(2H)-ones (Chapter 4), whereas substrates with the indole 2-position blocked provided access to substituted 4H-pyrrolo[3,2,1-ij]quinolin-4-ones (Chapter 5).

Employing a chiral pool strategy, enantiospecific syntheses of di- and triquinanes have been accomplished. α-Campholenaldehyde 95, readily available from the abundantly available monoterpene α-pinene 94, has been utilised as the chiral starting material. To begin with, enantiospecific synthesis of the diquinane 134 has been developed employing Nazarov cyclisation of the cross-conjugated dienone 132 as the key reaction (Scheme 37).71 Synthesis of the dienone 132 was accomplished by selenium dioxide mediated oxidation of the olefinic methyl group in α-campholenyl methyl ether 130, followed by further elaboration of the resultant aldehyde 131. OMe P2O5 MsOH The Nazarov cyclisation strategy has been further extended, as depicted in Scheme 38, for the synthesis of the triquinane enones 145 and 146 via the cross conjugated enone 144.71 The dienone 144 was obtained from the diquinane 136, which is readily available from campholenaldehyde 95 via an intramolecular rhodium carbenoid CH insertion reaction. Of the three methyl groups in campholenaldehyde 95, the olefinic methyl group can easily be functionalised, for example, via allylic oxidation. However, the remaining two tertiary methyl groups are difficult to functionalise, and there is no report in the literature on the utility of these two gem dimethyl groups either for functionalisation or for further elaboration, and remained only as gem dimethyl group in the products. It was conceived that it could be possible to utilise the tertiary methyl carbon for the ring construction via an intramolecular rhodium carbenoid γ-CH insertion reaction. To test the hypothesis, campho¬lenaldehyde 95 was converted into the diazoketone 165. Treatment of the diazoketone 165 with a catalytic amount of rhodium acetate furnished the diquinane 166, via a highly regio-and stereoselective insertion of the intermediate rhodium carbenoid in the CH bond of the tertiary methyl group, which is located cis with respect to the diazoketone, Scheme 39.72 As an application of the Nazarov cyclisation mediated synthesis of the diquinane 134, enantiospecific synthesis of the analogues of capnellenes, ABC and ABD ring systems of aberraranes have been carried out. A methyl cuprate reaction on the enone 134 generated the key intermediate, the ketone 169. A ring-closing metathesis (RCM) based cyclo¬pentannulation has transformed the diquinane 169 into the analogue of capnellene 175, as well as the analogue 197 of the ABC ring system of aberrarane. On the other hand, a Wacker reaction-intramolecular aldol condensation based spirocyclohexannulation transformed the diquinane 169 into an analogue 201 of the ABD ring system of aberrarane, Scheme 40.73 Finally, degradation of the two additional carbon atoms present on the A-ring furnished the ABC and ABD ring systems 235 and 238 of aberrarane, Scheme 41.(For structural formula pl refer the abstract pdf file)

Nous avons développé deux méthodes originales de synthèse de cyclopenténones fonctionnalisées et découvert de nouveaux réarrangements d’alcools 1-styryl propargyliques catalysés par des acides.Ce travail de thèse a aussi permis de mettre en évidence les limitations d’une méthode de synthèse des flavaglines développée par des chercheurs de la compagnie Bayer. De plus, la resynthèse de certaines flavaglines et la synthèse d’une sonde de fluorescence originale ont permis de mieux caractériser le mode d’action et le potentiel thérapeutique des flavaglines pour leurs effets anticancéreux (notamment dans la résistance aux inhibiteurs de B-RAF), la régulation du canal TRPM6 et l’infection par le virus du Chikungunya. / We have developed two novel methods to prepare functionalized cyclopentenones and also discovered new acid-catalyzed rearrangements of 1-styryl propargylic alcohols. This work also explored the limitations of a method for the synthesis of flavaglines reported by Bayer researchers. Moreover, the re-synthesis of some flavaglines and the synthesis of an original fluorescence probe allowed some advances in the characterization of the mechanism of action and therapeutic potential of flavaglines for their anti-cancer effects (especially in the resistance to B6RAF inhibitors), the regulation of TRPM6 channel and the infection by Chikungunya virus.

La catalyse organométallique est l’un des outils les plus puissants de la synthèse chimique, car elle permet de réaliser des transformations sélectives et spécifiques selon le catalyseur employé. Dans ce contexte, les sels et complexes d’or ont émergé il y a une quinzaine d’années et se sont révélés très utiles et attractifs pour la synthèse organique, faisant preuve de propriétés particulières de type acide de Lewis à la fois π (alcyno- alcènophilie) et σ (oxo- azaphile). L’objectif initial de cette thèse a été d'approfondir l’étude de la réactivité de l’or au travers la mise au point de nouvelles réactions catalysées par l’or(I/III). Si la majorité des réactions développées en catalyse à l’or concerne des processus de type π, nous avons dans un premier temps, souhaité évaluer son potentiel dans une réaction qui repose sur une activation purement σ, la cyclisation de Nazarov. Cette réaction a ensuite été étendue à un processus de type cascade, combinant activations π et σ. De plus, la formation d’un sous-produit inattendu au cours de cette étude a orienté nos recherches vers un nouveau processus catalytique, le réarrangement de γ–acyloxy alcynylcétones en furanes. Par la suite, nous nous sommes aussi intéressés au potentiel de l’or dans les réactions asymétriques, ce qui a conduit au développement d’un nouveau type de complexes d’or chiraux basés sur des ligands de type NHC-oxazoline. Enfin, nous nous sommes proposés d’utiliser la spectroscopie RMN J-résolue hétéronucléaire (une méthode simple mais peu exploitée), pour répondre à des problèmes d’attribution structurale. / Organometallic catalysis is one of the most powerful tools in chemical synthesis, because, depending on the catalyst, it allows for selective and specific transformations. Thus, the reactivity of gold salts and complexes was revamped around fifteen years ago. Nowadays, they are considered as powerful and very attractive for organic synthesis, showing both π (alcyno- alcènophilie) and σ (oxo- azaphile) Lewis acid properties.The first objective of this thesis was to study the reactivity of gold catalysts by the development of new reactions catalyzed by gold(I/III). If most of the developed reactions in gold catalysis is related to π activation, we proved its potential in a reaction dealing with σ activation, the Nazarov cyclization. This reaction was then extended to a cascade process, combining both π and σ Lewis acidities. Moreover, the obtainment of an unexpected by-product during the study directed our research towards a new gold catalytic reaction, the formation of furans from γ-acyloxyalkynyl ketones. Subsequently, we were also interested in the potential of gold in asymmetric reactions, which led to the development of new chiral gold complexs, based on NHC-oxazoline type ligands. Finally, we proposed to use the heteronuclear J-resolved NMR spectroscopy (a simple but scarce method), to answer some structural assignment problems.

In this thesis, superconducting nanostructures for quantum detection of electromagnetic radiation are studied. In this regard, electrodynamics of topological excitations in 1D superconducting nanowires and 2D superconducting nanostrips is investigated. Topological excitations in superconducting nanowires and nanostrips lead to crucial deviation from the bulk properties. In 1D superconductors, topological excitations are phase slippages of the order parameter in which the magnitude of the order parameter locally drops to zero and the phase jumps by integer multiple of 2\pi. We investigate the effect of high-frequency field on 1D superconducting nanowires and derive the complex conductivity. Our study reveals that the rate of the quantum phase slips (QPSs) is exponentially enhanced under high-frequency irradiation. Based on this finding, we propose an energy-resolving terahertz radiation detector using superconducting nanowires. In superconducting nanostrips, topological fluctuations are the magnetic vortices. The motion of magnetic vortices result in dissipative processes that limit the efficiency of devices using superconducting nanostrips. It will be shown that in a multi-layer structure, the potential barrier for vortices to penetrate inside the structure is elevated. This results in significant reduction in dissipative process. In superconducting nanowire single photon detectors (SNSPDs), vortex motion results in dark counts and reduction of the critical current which results in low efficiency in these detectors. Based on this finding, we show that a multi-layer SNSPD is capable of approaching characteristics of an ideal single photon detector in terms of the dark count and quantum efficiency. It is shown that in a multi-layer SNSPD the photon coupling efficiency is dramatically enhanced due to the increase in the optical path of the incident photon.