For most of human history, precious metals such as gold, silver, and platinum were used as currency and jeweler. Beginning in the 20th century, with the onset of transition metal catalysis, chemists developed new methods to support industrial chemical synthesis. There are many notable examples, one is the Ziegler-Natta catalysts to perform olefin polymerization using titanium/aluminum-based systems. Another is the Fisher-Tropsch process to convert synthesis gas (CO/H2) into liquid hydrocarbons typically using cobalt, ruthenium, and iron. Also, the Haber-Bosch process where nitrogen and hydrogen gases are reacted in the presence of an iron catalyst to generate ammonia is a critically important process for the production of agricultural fertilizer worldwide. For precious transition metals such as gold, the first report of the metal being used in homogenous catalysis was in 1986. In this thesis, the application of gold homogenous into the synthesis of polycyclic carbocycles is being reported. This method was designed as a three-step one-pot sequence where an initial Diels-Alder reaction forms the first carbocycle with an embedded silyl enol ether moiety reactive to homogenous gold(I) catalysis. By selecting specific catalyst ligand and solvent conditions, selectivity between tri or steroid-like tetracycles was achieved via gold then Prins cyclizations or gold then Diels-Alder cyclizations. A combined total of 31 examples across 3 scopes was demonstrated using this divergent and modular strategy. This methodology aims to be applied in medicinal chemistry research in the synthesis of libraries of structurally related compounds baring resemblance to bioactive natural products. A related synthetic strategy was also used by our group in the total synthesis of salvinorin A. Initially isolated from Salvia divinorum in 1972, salvinorin A is trans neo-clerodane diterpene and was found to be a selective agonist of the kappa opioid receptor (κOR). This is unique compared to traditional morphine type opioids which are substrates of mu (μOR) and delta (δOR) opioid receptors. And as such, extensive work in medicinal chemistry has been published on utilizing salvinorin A as starting point towards the development of new analgesics. Our approach to synthesize salvinorin A centered around using a Diels-Alder reaction then gold cyclization to form the AB rings. The remaining C ring was formed via gold photoredox catalyzed radical cyclization, 1,2-addition of a furanyl organotitanium, and palladium catalyzed carbonylation. The formal synthesis of salvinorin A was completed in 21 steps by intercepting an intermediate in Hagiwara’s reported synthesis, and addition 3 steps would complete the total synthesis.

Ce mémoire de thèse est composé de deux parties distinctes ayant comme thématique commune, les réactions multicomposants (MCR). Nous nous sommes intéressés dans un premier temps au développement d’une nouvelle MCR conduisant à des dérivés de l’indole, hétérocycle rencontré dans de nombreuses substances naturelles et composés biologiquement actifs. Nous avons ainsi mis au point un nouvelle méthodologie MCR séquentielle, rapide et efficace permettant d’accéder sélectivement, à partir des trois mêmes substrats (un précurseur indolique, un alcyne vrai et un accepteur de Michael) à deux familles de composés : les cyclopent[b]indoles ou les pyrrolo[1,2-a]indoles par une simple inversion de l’ordre des réactions. Puis dans un deuxième temps, nous avons élaboré une nouvelle synthèse totale diastéréosélective de lignanes tétrahydrofuraniques trisubstitués, connus pour leur abondance dans la nature et leurs propriétés biologiques très variées. Cette synthèse courte est composée de trois étapes clés : une réaction de cyclofonctionnalisation multicomposants palladocatalysée, une déméthoxycarboxylation -élimination utilisant des conditions de Krapcho modifiées et une réaction de type Hayashi-Miyaura permettant d’introduire le deuxième groupement aryle. Cette dernière réaction d’addition conjuguée a représenté le défi de cette synthèse et a donc fait l’objet d’une étude particulière sur un substrat modèle. / This thesis was split in two parts with the same thematic: multicomponent reactions (MCR). In the first one, we were focused on the development of two novel MCR leading to indole derivatives, an important heterocycle with numerous biological properties. We elaborated two new sequential, rapid and efficient methodologies involving three same partners, an indolic precursor, a terminal alkyne and a Michael acceptor added in predetermined order. This sequence allowed us to obtain two type of heterocycles, cyclopent[b]indoles or pyrrolo[1,2-a]indoles. In the second one, we developed a new diastereoselective total synthesis of trisubstitued tetrahydrofurans-type lignans, known for their abundance in nature and diverse biological activities. This short and efficient synthesis was composed of three key steps: a palladium-catalyzed threecomponents cyclization step, a Krapcho demethoxycarboxylation-elimination procedure and a stereoselective rhodium-catalyzed conjugate addition of an aryl group. This Hayashi-Miyaura reaction has represented the synthetic challenge that we have firstly studied on a model substrate.