The unifying theme of this thesis is the exploitation of the reactivity of aryliodonium salts as electrophile transfer reagents. In the first part of the thesis, diaryliodonium salts are employed as arylation reagents for the enantioselective copper-catalysed arylative semipinacol rearrangement (SPR) of various tertiary allylic alcohols. This cascade reaction is a rare example of asymmetrically activating SPR using carbon electrophiles. Different substrate classes - including dihydropyran, indene and dihydronaphthalene moieties - are converted to enantioenriched beta-aryl spirocyclic ketones in excellent yields and enantioselectivities, and often as a single diastereomer. These are in turn useful functional handles for transformations into other moieties, including further rearrangements via Baeyer-Villiger oxidation. In the second part of this thesis, a two-step process for the macrocyclisation of native peptides via a non-natural linkage is developed. This study exploits previous work conducted in the group on the use of aryliodonium salts as methionine-selective diazoacetate transfer reagents. The functionalised methionine is in turn used for an intramolecular rhodium-catalysed insertion into tryptophan. Eventual translation onto solid-phase enables facile access into various macrocyclic peptides.

Three examples of bis(diaryliodonium) perfluorosulfonimide (BDI-PFSI) zwitterions have been prepared as a potential new class of ionic photo-acid generators for chemically amplified photoresist formulations.

Les maladies du système nerveux central (SNC) comme la sclérose en plaques, les accidents vasculaires cérébraux et les maladies neurodégénératives (Alzheimer et Parkinson) entraînent une réponse inflammatoire au niveau cérébrale appelée neuroinflammation. Ce phénomène peut avoir pour conséquence la limitation de la propagation de la maladie mais aussi la réparation et la régénération des tissus touchés. La microglie, principale défense du SNC, passe à un stade activé lors de phénomènes neuroinflammatoires et va libérer de nombreux facteurs neuroprotecteurs mais aussi pro-inflammatoires. Cette dualité d’action va ainsi maintenir un cercle vicieux, pouvant conduire à la mort neuronale. Il serait donc intéressant de comprendre le mécanisme de la neuroinflammation pour diagnostiquer et traiter au mieux les pathologies du SNC. Il existe plusieurs cibles moléculaires, parmi elles se trouvent la CycloOXygénase 2 (COX-2), une enzyme qui permet la formation de prostaglandines à partir de l'acide arachidonique, qui apparaît précocement et est fortement surexprimée en cas de neuroinflammation. Cette enzyme serait donc une cible de choix pour le développement d’outils d’imagerie dans le but de diagnostiquer les pathologies dans lesquelles les processus inflammatoires centraux sont présents et ce afin d’améliorer la prise en charge du patient. La tomographie d’émission de positons (TEP) est une technique d’imagerie fonctionnelle très sensible qui permet de quantifier de manière fine les variations d’activités métaboliques ou moléculaires. Cette technique requiert l’utilisation de radiotraceurs marqués avec un émetteur béta+. / Central nervous system (CNS) disorders as multiple sclerosis, stroke and neurodegenerative diseases (Alzheimer’s and Parkinson’s) lead to inflammatory response in the brain called neuroinflammation. This phenomenon usually should result in limiting the spread of the disease but also repair and regeneration of the affected tissues. Microglia, the main defense of the SNC, which is activated during a neurodegenerative event leading to the production of many factors including neuroprotectors but also pro-inflammatories. This duality of actions will thereby maintain endless vicious circle leading to neuronal death. It would be interesting to understand the neuroinflammation mechanism to better diagnose and treat CNS diseases. There are several molecular targets, among them are the CycloOXygenase 2 (COX-2), an enzyme which allows the formation of prostaglandins from arachidonic acid, which appears early and it is significantly overexpressed in case of neuroinflammation. This enzyme is therefore a good biological target for the development of imaging tools in order to diagnose pathologies in which central inflammatory processes are present in order to improve patient care. Postiron emission tomography (PET) is a very sensitive functional imaging technique that quantifies minute variations in metabolic or molecular activities. This technique requires the use of radiotracers labeled with a beta + emitter.

Made available in DSpace on 2014-08-20T14:30:12Z (GMT). No. of bitstreams: 1 Tese_Fabricio_Aulo_Ogliari.pdf: 990670 bytes, checksum: 3309e79bda50d0506e497074067ddfca (MD5) Previous issue date: 2009-07-10 / The present investigation evaluated the effect of the diphenyliodonium hexafluorphosphate (DPIHFP) on the radical polymerization of methacrylates. Rate of polymerization from binary and ternary photoinitiation systems, performance of such systems in the presence of solvent and its effects on the bonding strength to bovine dentin were investigated. As a model adhesive resin, a blend of Bis-GMA, TEGDMA and HEMA (50/25/25 %wt) was prepared. Real-time degree of conversion was performed in a Fourier transform infrared spectrometer. To assess the photoinitiator system efficiency in a dental adhesive composition, the adhesion between the model resin and bovine dentin was investigated using microtensile bond strength(μTBS). When CQ was used as photo-initiator, a slow polymerization reaction was observed. The addition of a second component (onium salt or amine) increases the polymerization rate and conversion independent on the co-initiator concentration. Ternary photo-initiator system showed an improvement on the polymerization rate of the dental adhesive model resin leading to high conversion in short photo-activation time.The addition of a solvent to the monomer blends decreased the polymerization kinetics, directly affecting the rate of polymerization, delaying vitrification, and attenuating the Trommsdorf effect. The introduction of DPIHFP displayed a strong increase in reaction kinetics, reducing the solvent inhibition effect. After one year of storage, the μTBS values of the group CQ+EDAB+DPIHFP showed significantly higher bond strength(p<0.05) than CQ, CQ+DPIHFP and CQ+EDAB groups and no difference from commercial adhesive group. The ternary photoinitiation system with DPIHFP maintained increased bond strength to dentin of model self-etching adhesive systems after one year of aging / O objetivo do presente projeto foi avaliar o uso do hexafluorfosfato de difeniliodônio (DPIHFP) na polimerização radicalar de metacrilatos para aplicação odontológica. Para tal fim, foram considerados: aspectos relacionados ao potencial de sensibilização do DPIHFP pela canforoquinona; velocidade da reação de polimerização em sistemas binários e ternários; efeito em sistemas contendo solvente orgânico; e,influência nos valores e estabilidade da resistência de união ao tecido dentinário. Uma resina adesiva modelo constituída de 50% de Bis-GMA, 25% de TEGDMA e 25% de HEMA em massa foi formulada e utilizada em todos os experimentos realizados. Para a avaliação da cinética de conversão foram realizadas análises em espectroscopia no infravermelho em tempo real (RT-FTIR).Para a avaliação da resistência de união em dentina bovina, foram realizados ensaios de resistência de união à microtração na configuração de palitos, após 24 horas e 1 ano de realização das restaurações. Quando CQ foi utilizada como fotoiniciador, uma lenta reação de polimerização foi observada, sendo que a adição do DPIHFP como co-iniciador promoveu um aumento na reatividade do sistema, independentemente da concentração utilizada. A utilização de DPIHFP no sistema de fotoiniciação promoveu um aumento expressivo na reatividade do sistema, aumentando a taxa de polimerização máxima e o grau de conversão final do material. Adicionalmente, o DPIHFP reduziu o efeito inibitório provocado pela presença de solvente durante a polimerização, mantendo as taxas de polimerização semelhantes ao controle sem solvente. Quando o DPIHFP foi introduzido em um adesivo odontológico, foi observado um aumento significativo dos valores de resistência de união, sendo que estes valores mantiveram-se constantes em avaliação após 1 ano

Hypervalent iodine (HVI) reagents are easily accessed, highly tunable, mild, selective oxidants that are less toxic and more environmentally benign compared to their heavy metal counterparts. λ3-Iodanes, which possess an iodine center bound to one aryl substituent and two heteroatom ligands, have been the subject of recent interest due to their electrophilicity and hypernucleofugality. A central focus of the Wengryniuk laboratory has been the further development and application of a class of electrostatically activated (bis)cationic nitrogen-ligated HVI (N-HVI) reagents. N-HVIs feature datively bound heterocyclic ligands which results in dramatically enhanced electrophilicity and redox potentials. Despite being a highly tunable platform for reagent development, N-HVIs remain a relatively underexplored class of λ3-iodanes. This dissertation focuses on demonstrating N-HVI’s synthetic potential and developing novel variants to enhance their synthetic utility. Chapter 1 of this dissertation serves as a general background and introduction to nitrogen-ligated HVI reagents. Chapter 2 outlines our efforts in N-HVI library expansion, novel syntheses, and characterization. With a library of 33 novel N-HVIs in hand, ligand effects on N-HVI reactivity were analyzed via qualitative and quantitative methods. Chapter 3 describes our first synthetic application of N-HVIs in the development of novel oxidative rearrangements of simple and complex cyclic alcohols. This chapter describes the chemoselective ring expansion of 2° and 3° cyclic alcohols accessing medium-sized cyclic acetal products in good to excellent yields with applicability to Complexity-to-Diversity (CTD) efforts. Chapter 4 demonstrates our initial efforts toward the development of another synthetic method where the functionalized N-heterocyclic ligands of the N-HVIs can be regioselectivity incorporated into a molecule following N-HVI activation of an olefin. The pyridinium lactone salts formed from olefinic acids were isolated in excellent yields via simple trituration, supplying a synthetically useful functional handle that was easily derivatized via known methods. These four chapters summarize the current state of the research with nitrogen-ligated HVI salts, expand upon our initial publications to highlight the development of novel heterocyclic syntheses, and provide a useful guide to further explore the reactivity of these tunable reagents. / Chemistry

Le motif fluoropyridine est très fréquent dans les molécules d’intérêt thérapeutique et diagnostique pour l’imagerie par tomographie par émission de positons. Bien que les 3/5-[18F]fluoropyridines soient a priori plus stables in vivo que leurs analogues radiofluorés en position 2, 4 ou 6, leur radiosynthèse par voie nucléophile à partir du [18F]fluorure reste difficile et peu documentée. Dans ce contexte, les travaux ont porté sur l’étude du radiomarquage au fluor-18 de 3/5-fluoropyridines par radiofluoration de précurseurs iodoniums. Dans une première partie, la préparation d’une vingtaine de sels de iodonium possédant une structure pyridine ou pyridinium différemment substituée, a été mise au point. Une seconde partie a été dédiée à l’optimisation de la réaction de radiofluoration des sels de iodoniums. Cette étude a conduit à la mise en évidence du rôle important du TEMPO et de la base K2CO3 dans cette réaction. Enfin, la dernière partie a été consacrée à la radiosynthèse de 3/5-[18F]fluoropyridines portant des groupements carboxamides ou aminés par une approche multi-étape. L’ensemble des résultats ont montré que la radiofluoration de triflates de iodonium en présence de TEMPO était une méthode efficace, générale et robuste de radiosynthèse de 3/5-[18F]fluoropyridines. Cette méthode a été transposée avec succès sur deux automates de synthèse. / The fluoropyridinyl moieties have become of increasing importance in the development of drug candidates as well as of radiotracers for positron emission tomography (PET) imaging after radiolabeling with fluorine-18. Although 3/5-[18F]fluoropyridines are more stable in vivo than their 2,4 or 6 radiofluorinated analogues, their radiosynthesis by nucleophilic pathway from cyclotron produced [18F]fluoride remains difficult and poorly documented. In this context, the work focused on the development of a robust and general route to 3/5-[18F]fluoropyridines based on the radiofluorination of iodonium precursors. In a first part, the preparation of about twenty iodonium salts containing a pyridine or pyridinium scaffold, has been developed. A second part was devoted to the optimization of the radiofluorination reaction of iodonium salts. This study highlighted the important role of TEMPO and K2CO3 in this reaction. Finally, the last part was dedicated to the radiosynthesis of 3/5-[18F]fluoropyridines bearing carboxamide or amine groups according to a multistep approach. All the results showed that radiofluorination of iodonium triflates in the presence of TEMPO was an efficient, general and robust method for the radiosynthesis of 3/5-[18F]fluoropyridines. This method was also successfully transposed on two automated systems.

A arilação seletiva de compostos orgânicos confere-lhes propriedades com amplas aplicações: em compostos de atividade biológica, inibidora da protease do vírus HIV-1, e de interesse como agroquímicos ou na engenharia de materiais. Em razão disso, novos métodos e reagentes tem sido desenvolvidos com essa finalidade. Sabe-se que a N-arilação de várias aminas, catalisadas por paládio, com haletos de arila e triflatos é tida como ferramenta importante a disposição do químico sintético. Do mesmo modo, publicou-se que a N-arilação de certos -amino ácidos por haletos de arila, procede-se facilmente quando catalisada por CuI. Alternativamente, a literatura cita outros métodos eficientes usando ácidos borônicos, compostos arilbismuto e compostos organochumbo. Neste trabalho foi estudada a arilação seletiva de ânions ambidentados pelo sal de iodo polivalente cloreto de difenil iodônio, em diferentes condições de reação, visando a otimização da síntese: 1) reação térmica (agitação magnética), sem catalisador, e em diferentes solventes, ou mistura de solventes; 2) reação sonoquímica, sem catalisador e em diferentes soluções; 3) reação térmica e sonoquímica na presença de catalisador CuCl (10%). Sacarinato de sódio, acesulfame de potássio, e ftalimida potássica foram escolhidos como ânions ambidentados derivados de sulfoimidas e imidas a serem arilados. No caso de N-fenil sacarina a quemiosseletividade e o melhor rendimento são observados com acetonitrila/água (1:1, v/v), sob refluxo para formação do par iônico intermediário (ou o iodano correspondente), seguido por fusão térmica na ausência de solvente. O acesulfame potássico, por sua vez, forneceu seletivamente produtos de N- ou O-fenilação, de acordo com as seguintes condições estabelecidas: 1) produto de fenilação por via térmica ou sonoquímica em etanol; 2) produto de O-fenilação, por via térmica ou sonoquímica em acetonitrila. A ftalimida potássica, na ausência de catalisador, é arilada em baixos rendimentos. A melhor condição de síntese é encontrada com acetonitrila e CuCl (10%), sendo 92% o rendimento por via sonoquímica e 78% por via térmica. A seletividade verificada foi analisada em termos das interações dos ânions ambidentados e dos solventes em questão. / The arylation of organic compounds gives place to a wide number of applications: concerning to their biological properties as HIV-1, protease inhibitor, as well as synthetic intermediates in pharmaceuticals, agrochemical and polymer chemistry. New methodologies and reagents have been developed as consequence of this. It is already known that N-arylation of several amines, catalyzed by palladium, with aryl halides and trifflates is a valuable tool to various reported organic synthesis. In the same way, it has been published that the N-arylation of certain -amino acids by aryl halides, proceeds smoothly when catalized by CuI. Alternatively, the literature reports other efficient methods using boranic acids, arylbismuth and organolead compounds. In the present work, it was studied the selective arylation of ambident anions by hypervalent iodine salts (chloride of diphenyl iodonium), in a different set of conditions, seeking the synthesis optimizations: 1) thermal reactions (silent mode, magnetic stirring), without catalyst, and, in different solvents or mixture of then; 2) sonochemical reactions, without catalyst, and in a different solvent composition; 3) thermal and sonochemical reactions carried out in the presence of (10%) CuCl as the catalyst. Sodium saccharinate, acessulfame K and potassium phthalimide were chosen as the ambident anions (derived from sulfonimides and imide functional groups) to be studied. In the N-phenyl saccharin case the chemioselectivity was achieved along the best yields when water/acetonitrila (1:1, v/v) solvent was employed in the step to form the ion pair (or the 3-iodane, intermediate), followed by the thermal fusion in the absence of solvent. The acessulfame K, for its turn, supplied selectively products of N- and O-arylation under the following established conditions: 1) N-phenylation in etanol through thermal and sonochemical approach; 2) O-phenylation product, in acetonitrila, by thermal and sonochemical method. Finally, arylation of potassium phthalimide with diaryliodonium is sluggish and gives low yields without catalyst. The best protocol to this synthesis was found with the solvent acetonitrile and (10%) CuCl catalyst addition, being 92% the yield of sonochemical reaction and 78% of the thermal one. The selectivity achieving was analyzed in accord with the solution interaction between the ambident anion and the solvent molecules.

A arilação seletiva de compostos orgânicos confere-lhes propriedades com amplas aplicações: em compostos de atividade biológica, inibidora da protease do vírus HIV-1, e de interesse como agroquímicos ou na engenharia de materiais. Em razão disso, novos métodos e reagentes tem sido desenvolvidos com essa finalidade. Sabe-se que a N-arilação de várias aminas, catalisadas por paládio, com haletos de arila e triflatos é tida como ferramenta importante a disposição do químico sintético. Do mesmo modo, publicou-se que a N-arilação de certos -amino ácidos por haletos de arila, procede-se facilmente quando catalisada por CuI. Alternativamente, a literatura cita outros métodos eficientes usando ácidos borônicos, compostos arilbismuto e compostos organochumbo. Neste trabalho foi estudada a arilação seletiva de ânions ambidentados pelo sal de iodo polivalente cloreto de difenil iodônio, em diferentes condições de reação, visando a otimização da síntese: 1) reação térmica (agitação magnética), sem catalisador, e em diferentes solventes, ou mistura de solventes; 2) reação sonoquímica, sem catalisador e em diferentes soluções; 3) reação térmica e sonoquímica na presença de catalisador CuCl (10%). Sacarinato de sódio, acesulfame de potássio, e ftalimida potássica foram escolhidos como ânions ambidentados derivados de sulfoimidas e imidas a serem arilados. No caso de N-fenil sacarina a quemiosseletividade e o melhor rendimento são observados com acetonitrila/água (1:1, v/v), sob refluxo para formação do par iônico intermediário (ou o iodano correspondente), seguido por fusão térmica na ausência de solvente. O acesulfame potássico, por sua vez, forneceu seletivamente produtos de N- ou O-fenilação, de acordo com as seguintes condições estabelecidas: 1) produto de fenilação por via térmica ou sonoquímica em etanol; 2) produto de O-fenilação, por via térmica ou sonoquímica em acetonitrila. A ftalimida potássica, na ausência de catalisador, é arilada em baixos rendimentos. A melhor condição de síntese é encontrada com acetonitrila e CuCl (10%), sendo 92% o rendimento por via sonoquímica e 78% por via térmica. A seletividade verificada foi analisada em termos das interações dos ânions ambidentados e dos solventes em questão. / The arylation of organic compounds gives place to a wide number of applications: concerning to their biological properties as HIV-1, protease inhibitor, as well as synthetic intermediates in pharmaceuticals, agrochemical and polymer chemistry. New methodologies and reagents have been developed as consequence of this. It is already known that N-arylation of several amines, catalyzed by palladium, with aryl halides and trifflates is a valuable tool to various reported organic synthesis. In the same way, it has been published that the N-arylation of certain -amino acids by aryl halides, proceeds smoothly when catalized by CuI. Alternatively, the literature reports other efficient methods using boranic acids, arylbismuth and organolead compounds. In the present work, it was studied the selective arylation of ambident anions by hypervalent iodine salts (chloride of diphenyl iodonium), in a different set of conditions, seeking the synthesis optimizations: 1) thermal reactions (silent mode, magnetic stirring), without catalyst, and, in different solvents or mixture of then; 2) sonochemical reactions, without catalyst, and in a different solvent composition; 3) thermal and sonochemical reactions carried out in the presence of (10%) CuCl as the catalyst. Sodium saccharinate, acessulfame K and potassium phthalimide were chosen as the ambident anions (derived from sulfonimides and imide functional groups) to be studied. In the N-phenyl saccharin case the chemioselectivity was achieved along the best yields when water/acetonitrila (1:1, v/v) solvent was employed in the step to form the ion pair (or the 3-iodane, intermediate), followed by the thermal fusion in the absence of solvent. The acessulfame K, for its turn, supplied selectively products of N- and O-arylation under the following established conditions: 1) N-phenylation in etanol through thermal and sonochemical approach; 2) O-phenylation product, in acetonitrila, by thermal and sonochemical method. Finally, arylation of potassium phthalimide with diaryliodonium is sluggish and gives low yields without catalyst. The best protocol to this synthesis was found with the solvent acetonitrile and (10%) CuCl catalyst addition, being 92% the yield of sonochemical reaction and 78% of the thermal one. The selectivity achieving was analyzed in accord with the solution interaction between the ambident anion and the solvent molecules.

Les cyclopropanes sont des motifs d’une grande importance puisqu’ils sont présents dans plusieurs molécules biologiquement actives en plus d’être de puissants intermédiaires dans la synthèse de molécules complexes. Au cours de cet ouvrage, nous avons développé une nouvelle méthode générale pour la synthèse d’ylures d’iodonium de malonates, soit d’importants précurseurs d’esters cyclopropane-1,1-dicarboxyliques. Ainsi, à l’aide de ces ylures, une méthode très efficace pour la synthèse d’esters cyclopropane-1,1-dicarboxyliques racémiques a été développée. Des travaux ont aussi été entrepris pour la synthèse énantiosélective de ces composés. Par ailleurs, les esters cyclopropane-1,1-dicarboxyliques ont été utilisés dans le développement de deux nouvelles méthodologies, soit dans une réaction de cycloaddition (3+3) avec des imines d’azométhines et dans la formation d’allènes par l’addition-1,7 de cuprates. Nous avons aussi poursuivi l’étude synthétique du cylindrocyclophane F impliquant l’utilisation de cyclopropanes pour le contrôle des centres chiraux. Ainsi l’addition-1,5 d’un cuprate sur un ester cyclopropane-1,1-dicarboxylique a été utilisée comme l’une des étapes clés de notre synthèse. L’autre centre chiral a pu être contrôlé par l’hydrogénolyse sélective d’un cyclopropylméthanol. Ces études ont, par ailleurs, mené au développement d’une nouvelle réaction d’arylcyclopropanation énantiosélective utilisant des carbénoïdes de zinc générés in situ à partir de réactifs diazoïques. Cette méthode permet d’accéder très efficacement aux cyclopropanes 1,2,3-substitués. De plus, nous avons développé la première réaction de Simmons-Smith catalytique en zinc menant à un produit énantioenrichi. / Cyclopropanes are important scaffolds as they are present in many biologically actives compounds and they are useful intermediates in the synthesis of complex molecules. In this thesis, we developed a novel general method for the synthesis of iodonium ylides of malonates, which are important precursors in the synthesis of cyclopropane-1,1-dicarboxylic esters. From these ylides, a method to generate racemic cyclopropane-1,1-dicarboxylic esters very efficiently was developed. Further works was also achieved on an asymmetric version of this reaction. Cyclopropane-1,1-dicarboxylic esters were used to develop two new methods: a (3+3) cycloaddition reaction with azomethine imines and the formation of allenes by the 1,7-addition of cuprates. We also continued our studies towards the total synthesis of cylindrocyclophane F, which use the cyclopropanes to control all chiral centers. The 1,5-addition of a cuprate on a cyclopropane-1,1-dicarboxylic ester was utilized as one of the key steps of our synthesis. The other chiral centre was controlled by the hydrogenolysis of a cyclopropylmethanol. Moreover, these studies led to the development of a novel highly enantioselective arylcyclopropanation reaction using zinc carbenoids generated in situ from diazo compounds. This method allows the efficient access to 1,2,3-substituted cyclopropanes. Moreover, we developed the first Simmons-Smith reaction using a catalytic amount of zinc to produce an enantioenriched product.

Les cyclopropanes sont des motifs d’une grande importance puisqu’ils sont présents dans plusieurs molécules biologiquement actives en plus d’être de puissants intermédiaires dans la synthèse de molécules complexes. Au cours de cet ouvrage, nous avons développé une nouvelle méthode générale pour la synthèse d’ylures d’iodonium de malonates, soit d’importants précurseurs d’esters cyclopropane-1,1-dicarboxyliques. Ainsi, à l’aide de ces ylures, une méthode très efficace pour la synthèse d’esters cyclopropane-1,1-dicarboxyliques racémiques a été développée. Des travaux ont aussi été entrepris pour la synthèse énantiosélective de ces composés. Par ailleurs, les esters cyclopropane-1,1-dicarboxyliques ont été utilisés dans le développement de deux nouvelles méthodologies, soit dans une réaction de cycloaddition (3+3) avec des imines d’azométhines et dans la formation d’allènes par l’addition-1,7 de cuprates. Nous avons aussi poursuivi l’étude synthétique du cylindrocyclophane F impliquant l’utilisation de cyclopropanes pour le contrôle des centres chiraux. Ainsi l’addition-1,5 d’un cuprate sur un ester cyclopropane-1,1-dicarboxylique a été utilisée comme l’une des étapes clés de notre synthèse. L’autre centre chiral a pu être contrôlé par l’hydrogénolyse sélective d’un cyclopropylméthanol. Ces études ont, par ailleurs, mené au développement d’une nouvelle réaction d’arylcyclopropanation énantiosélective utilisant des carbénoïdes de zinc générés in situ à partir de réactifs diazoïques. Cette méthode permet d’accéder très efficacement aux cyclopropanes 1,2,3-substitués. De plus, nous avons développé la première réaction de Simmons-Smith catalytique en zinc menant à un produit énantioenrichi. / Cyclopropanes are important scaffolds as they are present in many biologically actives compounds and they are useful intermediates in the synthesis of complex molecules. In this thesis, we developed a novel general method for the synthesis of iodonium ylides of malonates, which are important precursors in the synthesis of cyclopropane-1,1-dicarboxylic esters. From these ylides, a method to generate racemic cyclopropane-1,1-dicarboxylic esters very efficiently was developed. Further works was also achieved on an asymmetric version of this reaction. Cyclopropane-1,1-dicarboxylic esters were used to develop two new methods: a (3+3) cycloaddition reaction with azomethine imines and the formation of allenes by the 1,7-addition of cuprates. We also continued our studies towards the total synthesis of cylindrocyclophane F, which use the cyclopropanes to control all chiral centers. The 1,5-addition of a cuprate on a cyclopropane-1,1-dicarboxylic ester was utilized as one of the key steps of our synthesis. The other chiral centre was controlled by the hydrogenolysis of a cyclopropylmethanol. Moreover, these studies led to the development of a novel highly enantioselective arylcyclopropanation reaction using zinc carbenoids generated in situ from diazo compounds. This method allows the efficient access to 1,2,3-substituted cyclopropanes. Moreover, we developed the first Simmons-Smith reaction using a catalytic amount of zinc to produce an enantioenriched product.