Ce manuscrit présente le développement de systèmes électrophiles mettant en jeu des complexes π-acides de Lewis à base d'or ou de platine et des ions halogéniums et leur application dans des processus d'activation de triples liaisons C-C (réactions de cycloisomérisation stéréosélective d'ènynes en présence ou en l'absence d'un nucléophile externe et réactions d'halocarbocyclisation) et de liaisons C-H (réactions d'acyloxylation d'arènes encombrés). L'emploi d'un système catalytique composé d'un complexe bimétallique d'or portant un ligand chiral (R)-4-MeO-3,5-(t-Bu)2C6H2-MeOBIPHEP et d'un sel d'argent a permis d'accéder à des dérivés méthylènecyclopentane en présence de nucléophiles externes et à des bicyclo[4.1.0]heptènes avec d'excellents excès énantiomériques. La méthode développée a pu être appliquée à la synthèse formelle d'une molécule pharmaceutique possédant des propriétés antidépressives : GSK1360707F. Le développement d'une méthodologie combinatoire a permis de rechercher rapidement des systèmes ligand bidente/ligand monodente/Pt permettant de réaliser ces transformations de manière stéréosélective. Cette méthode a également été utilisée pour rechercher des associations de ligands pour la synthèse de bicyclo[3.1.0]hexanones par cycloisomérisation d'ènynes-1,5. Le remplacement d'un complexe cationique par un ion halogénium a été étudié pour des réactions d'halocarbocyclisation et a permis de synthétiser des iodocyclopentènes fonctionnalisés par iodocyclisation en présence de N-iodosuccinimide. Cette méthode a pu être appliquée à l'approche synthétique d'un analogue contraint de la Combrétastatine A4. L'activation de liaisons C-H sp² grâce au complexe (Ph3P)AuCl en présence d'un oxydant de la famille des hypervalents de l'iode a permis de réaliser des réactions d'acétoxylation et d'acyloxylation de noyaux aromatiques encombrés avec des rendements modestes à bons.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

This thesis describes the development of transition metal catalyzed transformations towards the synthesis of stereochemically rich motifs and heterocycles. The main themes present throughout this thesis are rhodium-catalysis in reactions of boronic acids with alkenes and alkynes, the use of alkynes as a key motif in the synthesis of heterocycles, and the use of domino and one-pot processes to effect high efficiency in multistep transformations. In Chapter 1, a rhodium-catalyzed desymmetrization of diazabicyclic alkenes with boronic acids is discussed. In this work a chemodivergent and enantioselective process for the synthesis of substituted cyclopentenes and cyclopentanes is developed. Both the chemo- and the enantioselectivity of the reaction are shown to be highly dependent on the phosphine ligand structure. The observed reactivity of rhodium is further applied to a domino reaction to synthesize highly substituted benzofuranones. In Chapter 2, the reactivity of boronic acids and alkynes under rhodium catalysis is exploited as a key step to access polycyclic motifs. In the first part of this chapter the development of a domino process using both rhodium and palladium catalysis is described. Detailed mechanistic investigations allow some insight into the interactions between two catalysts. In the last part of this chapter, preliminary experiments in the application of multimetallic catalysis in the synthesis of azadibenzoxepines are discussed. Chapter 3 summarizes work on the arylation of propargylic alcohols with boronic acids under rhodium catalysis. This reaction is shown to proceed with high regioselectivity and can be conducted under mild conditions. The resulting allylic alcohols are shown to be versatile motifs and are applied in a synthesis of indenes and quinolines. In the final chapter of this thesis, iodotriazoles are explored as key intermediates in the synthesis of fused triazole-containing heterocycles. Palladium-catalyzed cyclization, either through C-H functionalization or through Heck coupling, is achieved. Furthermore, it is shown that the copper-catalyzed azide-alkyne cycloaddition and palladium-catalyzed C-H arylation can be combined into a one-pot process.

A synthetic approach to produce lysergic acid by virtue of an asymmetric ring opening (ARO) of symmetrical 3,6-disubstituted-7,10-hydroxymethyl bridgehead substituted oxabicycles is described. The use of a Rhodium(I)/JosiPhos(R,S) catalyst system to effect an ARO using an amine nucleophile furnishes an enantiopure tetrahydronapthalene intermediate with the amine conveniently installed at the 6 position as in lysergic acid, with appropriate stereochemistry; further which, two subsequent annulations are necessary to form the fused 3,5-substituted indole and tetrahydropyridine to complete the synthesis. Progress of this work is described herein along with future directions. The second chapter in this thesis describes the modular and stereoselective synthesis of tetrasubstituted helical alkenes via a palladium-catalyzed domino reaction under Catellani conditions. These helical alkenes possess potentially interesting photochemical properties as molecular motors / switches, and can be applicable in the materials sciences as molecular machines.

A synthetic approach to produce lysergic acid by virtue of an asymmetric ring opening (ARO) of symmetrical 3,6-disubstituted-7,10-hydroxymethyl bridgehead substituted oxabicycles is described. The use of a Rhodium(I)/JosiPhos(R,S) catalyst system to effect an ARO using an amine nucleophile furnishes an enantiopure tetrahydronapthalene intermediate with the amine conveniently installed at the 6 position as in lysergic acid, with appropriate stereochemistry; further which, two subsequent annulations are necessary to form the fused 3,5-substituted indole and tetrahydropyridine to complete the synthesis. Progress of this work is described herein along with future directions. The second chapter in this thesis describes the modular and stereoselective synthesis of tetrasubstituted helical alkenes via a palladium-catalyzed domino reaction under Catellani conditions. These helical alkenes possess potentially interesting photochemical properties as molecular motors / switches, and can be applicable in the materials sciences as molecular machines.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

This thesis includes two topics. One is a low-power high-speed 8-bit pipelining CLA design using dual threshold voltage (dual- Vth) domino logic. The other is a low-cost digital I/Q separator for DVB-T receivers. A high speed and low power 8-bit CLA using dual- Vth domino logic blocks arranged in a PLA-like style with pipelining is presented. According to parallely precharge and sequentially evaluate in a cascaded set of domino logic blocks, transistors in the precharge part and the evaluation part of dual- Vth domino logic are, respectively, replaced by high Vth transistors to reduce subthreshold leakage current through OFF transistors, and low Vth transistors. Moreover, an nMOS transistor is inserted in the precharge phase of the output inverter such that the two-phase dual- Vth domino logic can be properly applied in a pipeline structure. Consequently, the proposed design keeps the advantage of high speed while attaining the effect of low power dissipation. A low-cost digital I/Q separator is presented in the second part of this thesis. Using digital I/Q separator in place of the traditional analog I/Q separator guarantees the design conquer gain and phase mismatch problems between the I and Q channels. The proposed design can berealized by inverters and shifters such that the goal of low cost can be achieved.

Nous avons réalisé une réaction domino qui a conduit à une diversité moléculaire importante avec de bons rendements et une large gamme de groupes fonctionnels. De plus, un contrôle total de la stéréochimie est exercé sur les centres introduits, ce qui a permis en particulier, la synthèse stéréocontrôlée de deux centres quaternaires adjacents.<br />Une amélioration a pu être apportée afin de diminuer la toxicité de la réaction, en remplaçant la moitié du tétra-acétate de plomb par du diacétate de iodo-benzène moins toxique.<br />Cette réaction permet ainsi l'élaboration de cyclohexanes hautement fonctionnalisés comportant jusqu'à cinq centres définis.<br />La famille des iridals (comportant plus de 30 représentants) s'est alors révélée une cible de choix pour l'utilisation de notre réaction domino en synthèse totale. Les iridals sont des triterpènes qui possèdent des propriétés biologiques importantes, principalement contre le cancer (un brevet a été déposé par une équipe de Montpellier). Les iridals ont tous en commun un noyau cyclohexane comportant quatre centres asymétriques adjacents, dont deux quaternaires, ce qui en fait des cibles synthétiques intéressantes.<br />Nous avons choisi l'iridal, molécule mère de la famille, comme première cible et nous proposons une approche de sa synthèse. La construction de la chaîne homofarnésyle est particulièrement traitée.

Alkenes are remarkably versatile motifs as they can be further functionalized by a vast array of addition, reduction, and oxidation reactions. Thus their efficient synthesis is highly desired. Over the past 35 years, the Suzuki-Miyaura cross-coupling reaction has emerged as a powerful synthetic tool for the formation of carbon-carbon bonds. Herein is described the development of a one-pot two-step protocol for the synthesis of (E)-alkenes comprising palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl or heteroaryl halides, including chlorides, with alkenyl pinacolboronates, prepared in situ via solvent-free zirconium-catalyzed hydroboration of terminal alkynes. Avoiding isolation of intermediates saves time and reduces waste. The regio- and stereochemistry of the alkene is set by initial hydrozirconation of the alkyne. Addition of water to the second step deactivates the zirconocene catalyst, which is otherwise deleterious to cross-coupling. Thus this sequence exploits the water tolerance of the Suzuki-Miyaura reaction.

Alkenes are remarkably versatile motifs as they can be further functionalized by a vast array of addition, reduction, and oxidation reactions. Thus their efficient synthesis is highly desired. Over the past 35 years, the Suzuki-Miyaura cross-coupling reaction has emerged as a powerful synthetic tool for the formation of carbon-carbon bonds. Herein is described the development of a one-pot two-step protocol for the synthesis of (E)-alkenes comprising palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl or heteroaryl halides, including chlorides, with alkenyl pinacolboronates, prepared in situ via solvent-free zirconium-catalyzed hydroboration of terminal alkynes. Avoiding isolation of intermediates saves time and reduces waste. The regio- and stereochemistry of the alkene is set by initial hydrozirconation of the alkyne. Addition of water to the second step deactivates the zirconocene catalyst, which is otherwise deleterious to cross-coupling. Thus this sequence exploits the water tolerance of the Suzuki-Miyaura reaction.