Homogenous Au(I)-catalysis has become a valuable synthetic tool to activate a host of unsaturated carbon functional groups towards nucleophilic addition. Over the course of the past two decades, many have embarked on new journeys within this field. Notably, the advancements in this field hinge on the development of new ligand systems that impart novel reactivity at the metal. Our group has focused on this area, as we have successfully demonstrated the utility of 1,2,3-triazoles as ligands for gold and a host of other transition metals and Lewis acids. With respect to gold catalysis, these ligands enhance the stability of the metal center, thus inhibiting typical reductive decomposition pathways that have plagued this field. The enhanced stability comes with a price though as higher temperatures can be required. We’ve addressed this challenge by discovering an interesting synergy between triazole-gold and Lewis acids, allowing us to overcome the lower reactivity of these catalysts. During my time as a graduate student, I have focused heavily on enlisting these catalytic systems for new reaction discovery. In my first experimental chapter, I was able to develop an interesting reaction cascade in which triazole-gold and secondary amine catalysts were used. I started with a well-known gold-catalyzed Claisen rearrangement of propargyl vinyl ether, yielding functionalized allenes. The identical oxidation state between these allenes and synthetically appealing dienals was an impetus to develop a new isomerization strategy. After screening various conditions, I was able to successfully execute this design. Most of the work I have been involved in over the past two years has surrounded a gold-catalyzed hydroboration to yield interesting hetercocycles containing a N-B bond. The N-B bond offers some unique properties as it is isoelectronic to a C-C double bond. Despite the simplicity in this design, it would become apparent early on in this research that mitigating the reducing strength of the starting materials was absolutely critical. Starting materials that were too strongly reducing led to rapid catalyst decomposition. Through thorough reaction screening, we have been able to identify a catalytic system that performs extremely well in this context. Ultimately, our goal in this work is to access 1,2-azaborines, which are isosteres of benzene. This compound exhibits aromaticity, as determined through structural and quantitative analyses by several groups. However, subtle differences in properties between the azaborine and benzene, such as its polarity, have intrigued many researchers across various disciplines. Moreover, the ubiquity of its carbonaceous parent in biological systems has prompted many to pursue new synthetic routes to access 1,2-azaborines.

L’objectif principal des travaux de recherche décrits dans ce manuscrit de thèse, est de concevoir de nouvelles méthodes de synthèse en chimie radicalaire et organométallique, de les associer dans une catalyse duale afin qu’elles puissent être appliquées à l’élaboration de briques moléculaires élaborées. Nous avons développé dans une première étude une alternative photocatalytique à la réaction de désoxygénation classique de Barton-McCombie d’alcools secondaires et tertiaires par l’hydrure de tributylétain. Celle-ci repose sur l’utilisation d’un précurseur O-thiocarbamate dérivé d’alcools pouvant être réduit par catalyse photorédox. Une étude mécanistique, basée sur des expériences de fluorescence et de voltammétrie cyclique, est aussi présentée. Dans une seconde étude, une élégante méthode de génération de radicaux alkyles non stabilisés, par photooxydation de « ate-complexes » de bore ou d’espèces hypervalentes à base de silicium est présentée. Ces radicaux sont piégés en présence d’accepteurs radicalaires ou engagés dans une catalyse duale avec des complexes de Nickel. / Visible-light photoredox catalysis has emerged as a very powerful strategy to generate radical species replacing more and more tin-mediated or stoichiometric redox methodologies. The main objective of the research described in this Ph. D. thesis is to develop new synthetic methodologies in radical and organometallic chemistry, and merge them in a dual catalysis process for the preparation of elaborated molecular building blocks. In a first study, we report a photocatalytic alternative of Barton-McCombie deoxygenation based on a visible-light photoreduction of O-thiocarbamates derived from secondary and tertiary alcohols. A mechanistic investigation is presented based on fluorescence quenching and cyclic voltammetry experiments. In a second study, a challenging method of generation of unstabilized alkyl radicals by photooxidation of borate salts or hypervalent silicon species is reported. These radicals are trapped by free radical scavengers or engaged in a photoredox/nickel dual catalysis.

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Nowadays, the requirement to design highly valuable compounds is undoubtedly one of the major challenges in the field of organic and organometallic chemistry. The use of the versatile and efficient N-heterocyclic carbenes (NHCs) combined with transition metals represents a key feature in modern organometallic chemistry and homogeneous catalysis. In the course of this thesis, the straightforward design and synthesis of a library of Pd(0) bearing NHC ligands was achieved. Their catalytic performances (Chapter 1) and their phosphorescence properties in solution (Chapter 2) were disclosed. Currently, cross-couplings are some of the most important types of reaction in palladium catalysis. The formation of highly hindered biaryls substrates is one of the main requirements in cross-coupling chemistry. The design and synthesis of a palladium dimer bearing a bulky NHC ligand can fulfil this proposal (Chapter 4). The development of new classes of ligands is a topic of interest. For this reason, normal, abnormal, remote and mesoionic N-heterocyclic carbenes copper complexes were investigated and their reactivity compared in the [3+2] cycloaddition of azides and alkynes (Chapter 7). Air and moisture stable Cu(I)-NHC species have also been compared to their silver analogues for the alkynylation of ketones (Chapter 9). The different reactivity of the two latter organometallic species (Cu and Ag) with ethyldiazoacetate reagent via the formation of carbenes or C-H activated product is presented in Chapter 8. Recently, the development of a bimetallic catalytic system is strongly considered and has high impact. For this reason, two dual catalytic transformations (Pd-NHC and Cu-NHC) were studied for the C-H arylation (Chapter 5) and the synthesis of substituted alkenes products via a relay or cooperative mechanisms (Chapter 6). The isolation of intermediates and mechanistic studies were examined in each of these studies.

Ce mémoire de thèse se concentre sur le développement de réactions multicatalysées impliquant une activation iminium et un transfert d’hydrogène réversible rédox-neutre pour la synthèse de briques moléculaires complexes énantioenrichies à partir de composés 1,3-dicarbonylés et d’alcools allyliques.Une cascade réactionnelle combinant un complexe de fer et une pyrrolidine chirale a été développée pour la préparation d’alcools g-fonctionnalisés énantioenrichis par une approche impliquant économie d’étapes et d’atomes. L’efficacité de cette méthode impliquant une catalyse duale ainsi qu’une étape de rétro-Claisen a été démontré dans la synthèse de fragments clés de produits naturels. Cette méthodologie a ensuite été complétée par une étude mécanistique expérimentale aboutissant à une meilleure compréhension du mécanisme de cette transformation et conduisant également au développement d’une catalyse triple impliquant deux complexes métalliques et un organocatalyseur. Par la suite, une nouvelle approche pour la synthèse de lactones énantioenrichies de taille de cycles moyens a été mise au point. Cette stratégie de synthèse est basée sur une addition-1,4- organocatalysée énantiosélective de Michael, suivie d’une réduction chimiosélective qui engendre une fragmentation de Claisen.Enfin, grâce aux méthodologies développées au cours de cette thèse, la synthèse totale d’un produit naturel, la floribundane B, a été étudiée. / This manuscript is focus on the development of multicatalyzed reactions involving iminium activation and reversible neutral hydrogen transfer reaction for the synthesis of complexe enantioenriched building blocks from allyl alcohols and 1,3-dicarbonyls.An unprecedented cascade catalysis combining an iron catalyst and a pyrrolidine-base catalyst is developed for the preparation of g-fonctionalized enantioenriched alcohols in a formal redox-, atom- and step-economical approach. The efficiency of this method involving a dual catalysis and a retro-Claisen xas further demonstrated in the short synthesis of several key fragments of biologically active natural products or odorant molecule. This methodolgy was then incremented by a experimental mechanistic study allowing a better understanding of the mechanism of this transformation and leading to a new catalytic systeminvolving three different catalysts (iron complex, copper and organocatalyst). Then, we focused on the development of a new synthetic approach to enantioenriched medium-sized lactones. This methodology is based on a 1,4-Michael addition of cycloalkane-1,3-diones to a,b-insaturated aldehydes. Then, a key chemoselective reductively triggered Claisen fragmentation occurred to generate desired lactones in a rapid manner.Finally, thanks to our methodology developed during this thesis, the total synthesis of floribundane B was studied.