This doctoral dissertation described herein will be comprised of two parts. The first portion will address our efforts towards the synthesis of [alpha]-amino carbonyls from silyl enol ethers and the second portion will describe our unrelated efforts towards the synthesis of proaporphine alkaloids. A full discussion of the relevant literature, experiments and development of the methodologies will be provided along with all relevant experimental data. Part I: The [alpha]-amino carbonyl moiety has great potential for being a very useful synthetic intermediate for the incorporation of nitrogen owing to the synthetic utility and versatility of the carbonyl functional group. Despite this potential the synthesis has long been problematic owing to their tendency to undergo condensation reactions. We aimed to synthesize them utilizing a protected carbonyl in the form of a triisopropylsilyl enol ether and an electrophilic nitrogen source that could incorporate the nitrogen via an ene-[2,3] sigmatropic reaction sequence. To this end we used an N-sulfinyl carbamate as an electrophilic source of nitrogen that could be utilized for a regiospecific allylic amination of alkenes or could be used to form a highly reactive sulfur diimide that could be used for the allylic amination of alkenes or silyl enol ethers. Part II: Many pharmacologically important and synthetically interesting alkaloids have been formed in nature by the o,p oxidative phenolic coupling of various benzyl-tetrahydroisoquinoline alkaloids. One major class of alkaloids derived from this generalized oxidation is the proaporphine alkaloids and they possess an acid labile spirocyclic-dienone system obtained from this coupling. These compounds have great potential for being used for their anesthetic properties. Despite the relative ease of synthesizing the benzylisoquinoline alkaloids the application of the biomimetic oxidative coupling to make the quaternary center of these compounds gives very poor yields. We opted to form this spiro-dienone system by using a two step Suzuki coupling-para phenolate alkylation methodology that had been used to synthesize the related alkaloids codeine and narwedeine. In doing this we opted to extend the practical application of this methodology by the displacement of an alcohol derived leaving group. / text

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La quinocarcine, la tétrazomine et la lémonomycine constituent une sous-famille appartenant à la famille des tétrahydroisquinoléines trisubstituées naturelles. Ce sont des puissants agents cytotoxiques et possèdent de nombreuses activités biologiques telles qu’antitumorales et antibiotiques. Leur complexité structurale, leurs intérêts biologiques ainsi que leur faible rendement d’extraction du milieu naturel font de ces molécules des cibles attrayantes pour les chimistes de synthèse.Ces trois molécules sont constituées d’une tétrahydroisoquinoléine différemment substitué fusionnée avec un diazabicycle[3.2.1]octane commun. Le but de ce projet était de mettre au point une stratégie commune à cette sous-famille et divergente grâce à la synthèse du diazabicyclooctane en premier. Une première stratégie faisant intervenir une aziridine n’a pas permis de construire le bicycle. Cet objectif a été réalisé grâce à une seconde stratégie. Elle repose sur une première cyclisation d’un hémiaminal puis d’une cyclisation par addition nucléophile d’un éther d’énol silylé sur un N-acylimmonium formé in situ au départ d’un N,S-acétal.Parallèlement à cette étude synthétique, nous avons mis au point une réaction multicomposant séquentielle qui permet l’accès rapide et général aux a-amidosulfures, comblant un manque dans la littérature. Ensuite nous avons étudié la réactivité de ces composés en tant que précurseurs simples de N-acylimines en conditions acides douces. Trois conditions réactionnelles, nous ont permis d’accéder à cette objectif : l’utilisation stœchiométrique d’acétate d’argent, catalytique d’acide phosphorique ainsi que le NIS en quantité stœchiométrique et catalytique. Cette dernière réaction est très attrayante. En effet, ce réactif doux et neutre permet l’élimination efficace du thiol formant la N-acylimine puis son activation pour se faire piéger in situ par un nucléophile. Les rendements atteints sont très hauts en moins de 5 minutes. / Quinocarcin, tetrazomin and lemonomycin constitute a subfamily belonging to the family of natural trisubstituted tetrahydroisquinolines. These are powerful cytotoxic agents and have many biological activities such antitumor and antibiotics. Their structural complexity, biological interests and their low efficiency of extraction of the natural environment make these molecules attractive targets for synthetic chemists.These three molecules are constituted of differently substituted tetrahydroisoquinoline diazabicycle merged with a [3.2.1] octane common. The purpose of this project was to develop a common strategy in this subfamily and divergent with the synthesis of diazabicyclooctane first.A first strategy involving an aziridine failed to build the bicycle. This objective was achieved through a second strategy. It is based on a first cyclization of hemiaminal followed by cyclization of nucleophilic addition of a silyl enol ether of an N-acylimmonium formed in situ from a N, S-ketal.Along with this synthetic study, we developed a multicomponent reaction sequence that allows quick general access to -amidosulfides, filling a gap in the literature. Then we studied the reactivity of these compounds as simple precursors of N-acylimines in mild acidic conditions. Three reaction conditions allowed us to reach this goal: the use of stoichiometric silver acetate, phosphoric acid as catalyst and NIS in catalytic and stoichiometric amount. This last reaction is very attractive. Indeed, this sof and neutral reagent allows the efficient removal of the thiol forming the N-acylimine and its activation to be trapped in situ by a nucleophile. The yields are very high in less than 5 minutes.