Vu l’importance des molécules fluorées dans différents domaines et vu la réactivité engendrée par le 4,4,4-trifluorobut-2-ynoate d’éthyle 1 lors des travaux antérieurs réalisés au laboratoire, nous avons décidé d’étudier le comportement de dérivé fluoré 1 vis-à-vis d’hydrure tributylétain sans l’emploi de catalyseurs ou d’additifs. Le but est d’accéder à de nouveaux synthons fluorés par voies originales.Après une étude préliminaire pour effectuer cette réaction d’hydrostannation dans les meilleures conditions, nous avons réalisé pour la première fois la synthèse totalement régio- et stéréosélective des vinylétains (Z)-2α et (Z)-2β par un simple choix de solvant et sans l’utilisation d’aucun additif. Ces résultats inédits et très encourageants, nous ont conduis à étendre cette stratégie à d’autres hydrures comme l’hydrure de diphénylphosphine et l’hydrure de triphénylgermane..Les vinylétains (Z)-2α et (Z)-2β- de configurations bien définies sont des réactifs de choix pour élaborer de nouvelles structures fonctionnelles trifluorométhylées. En effet, le couplage cupro-catalysé de ces vinylétains en présence d’une quantité catalytique de CuI (10 moles%) avec une variété de bromures d’allyles, de propargyles, d’aryles, de benzyles et d’alcynyles conduisent à une grande variété de composés fluorés jamais décrits dans la littérature.Les méthodes de synthèse développées dans ce travail sont originales et permettent la synthèse d’une grande famille de composés fluorés avec un moindre coût. / The development of a simple method to obtain perfluoroalkylated building blocks for their subsequent utilization in the synthesis of Rf-containing compounds is therefore essential to organofluorine chemistry. Perfluoroalkylated vinyl metals constitute an important class of these building blocks.In order to prepare a new perfluoroalkylated bulding blocks, we investigated transition metal-catalyzed-free hydrostannylation of ethyl 4,4,4-trifluorobut-2-ynoate 1. The hydrostannylation took place smoothly in the absence of additive, providing regioselectively high yields of the corresponding α or β stannylated alkenoates depending on the nature of the solvent used. Indeed, we have demonstrated that the hydrostannylation of 1 in hexane provided the β-stannylated product with high regioselectivity (>95%) and excellent yield (>97%). Using methanol as solvent, total α-regioselectivity of the hydrostannylation of 1 was observed, providing α -tributylstannylacrylate as the sole regioisomer in a nearly quantitative yield.Theses new vinyltins reagents readily undergo copper (I) catalyst coupling reactions with various electrophiles as allyl, propargyl, benzyl and alkynyl bromides to provide good yields of the new corresponding acrylates esters bearing a β-trifluoromethyl group.This method provided a new efficient entry to this important class of compounds

This thesis describes synthetic studies directed towards the total synthesis of the nakafuran and florlide marine natural products. Chapter One provides an overview of the importance of natural products to current medicinal chemistry and describes how the "supply issue" associated with these biologically derived compounds can be resolved through the process of total synthesis. Two families of marine natural products, the nakafurans and the florlides, are introduced as synthetic targets and strategies utilising a type II intramolecular Diels-Alder (IMDA) reaction to achieve their total synthesis are delineated. The efficient preparation of regio- and stereodefined vinyl coupling fragments via hydrostannylation and hydrohalogenation methodology is described in Chapter Two. The palladium-catalysed cross-coupling of these fragments, via Stille or Negishi coupling methodology, yielded dienes which were successfully advanced to IMDA triene precursors. Chapter Three describes investigation of the type II IMDA reaction to give bicyclo[4.3.1]decene carbocyclic skeletons. A facile acid-catalysed 6,7-alkene to 7,8-alkene olefinic isomerisation, via a proposed oxonium intermediate, and the inability to appropriately functionalise the desired adducts impeded progress along the synthetic route. Molecular modelling was conducted to investigate the causes of this unexpected reactivity. Investigations in Chapter Four describe the successful synthesis and cyclisation of homomethyl triene analogues prepared via application of enyne metathesis chemistry. The use of an exo-cyclopropylcarbinyl fragmentation was found to be unsuccessful as a means of installing the desired 6-methyl-bicyclo[4.3.1]decan-2-one core with a competing endo-ring expansion giving rise to a bicyclo[4.4.1]undecane ring system. Chapter 5 summarises the above results and gives a brief discussion of the future potential of this research to provide for a total synthesis of the nakafuran and florlide natural products.

This thesis describes synthetic studies directed towards the total synthesis of the nakafuran and florlide marine natural products. Chapter One provides an overview of the importance of natural products to current medicinal chemistry and describes how the "supply issue" associated with these biologically derived compounds can be resolved through the process of total synthesis. Two families of marine natural products, the nakafurans and the florlides, are introduced as synthetic targets and strategies utilising a type II intramolecular Diels-Alder (IMDA) reaction to achieve their total synthesis are delineated. The efficient preparation of regio- and stereodefined vinyl coupling fragments via hydrostannylation and hydrohalogenation methodology is described in Chapter Two. The palladium-catalysed cross-coupling of these fragments, via Stille or Negishi coupling methodology, yielded dienes which were successfully advanced to IMDA triene precursors. Chapter Three describes investigation of the type II IMDA reaction to give bicyclo[4.3.1]decene carbocyclic skeletons. A facile acid-catalysed 6,7-alkene to 7,8-alkene olefinic isomerisation, via a proposed oxonium intermediate, and the inability to appropriately functionalise the desired adducts impeded progress along the synthetic route. Molecular modelling was conducted to investigate the causes of this unexpected reactivity. Investigations in Chapter Four describe the successful synthesis and cyclisation of homomethyl triene analogues prepared via application of enyne metathesis chemistry. The use of an exo-cyclopropylcarbinyl fragmentation was found to be unsuccessful as a means of installing the desired 6-methyl-bicyclo[4.3.1]decan-2-one core with a competing endo-ring expansion giving rise to a bicyclo[4.4.1]undecane ring system. Chapter 5 summarises the above results and gives a brief discussion of the future potential of this research to provide for a total synthesis of the nakafuran and florlide natural products.