No description available.

No description available.

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.

Investigation of the catalytic formation, reactivity and synthetic scope of sp³-gem-organodimetallic palladio(II)/main group metal (main group metal = tributylstannyl, dialkylalumino) alkane species has been carried out. Insight was expanded regarding the inter- and intramolecular reactivity of vinylmetallic reagents in presence of transition metal catalysts. New Pd-catalysed methodologies for carbon-carbon bond formation were developed, such as cyclopropanation of strained olefins, as well as tandem vinylalane arylation/1,2-methyl transfer and 1,2-diarylation. On the one hand, geminal π-allylpalladio(II)/tributylstannylalkane intermediates are produced by oxidative addition of Pd(0) catalysts to α-tributylstannylpropenyl acetate derivatives. They adopt ambiphilic behaviour depending on the transition metal pre-catalyst, presence or absence of phosphine ligands, and reaction temperature. In presence of tetrakis(triphenylphosphine)palladium(0) with additional bidentate ligand, the carbenoid reactivity of these gem-organobismetallic species is exposed by reaction with dimethyl malonate. Deuterium-labeling studies demonstrated sequential functionalisation of the C-Sn and C-Pd bonds. Conversely, phosphine-free catalyst bis(dibenzylideneacetone)palladium(0) uncovers metal-carbene reactivity, and dimerisation and strained alkene cyclopropanation reactions are observed. The nature of the palladium catalyst controls the reactivity of the carbenoid species. Finally, bis(cyclooctadienerhodium(I) chloride) catalytically activates the alkenylstannane moiety, leaving the allylic acetate leaving group available for further transformations. On the other hand, gem-disubstituted trifluoromethanesulfonyloxy- and iodopalladio(II)/ dialkylaluminoneopentane species are generated by intramolecular migratory insertion of 2,2-disubstituted-1-butenyldialkylalanes with σ-arylpalladium(II) triflate and iodide intermediates. Using excess Lewis-basic 1,4-diazabicyclo[2.2.2]octane, electron-rich tris(para-methoxyphenyl)phosphine ligand and acetonitrile as solvent, tandem arylation/1,2-alkyl migration from aluminum to carbon affords 7-substituted-1-ethyl-1-methylindanes containing an all-carbon quaternary stereogenic centre in good yields. This reaction is tolerant of 6-aryl methyl ethers, thioethers and trimethylsilanes. Deuterium labeling established that protiodealumination of the key neopentyl(methyl)aluminum triflate intermediate is caused by the acetonitrile solvent. The organodimetallic species in that study were shown to be configurationally stable, hence the stereospecificity of the process that proceeds via carbopalladation, transmetalation and reductive elimination of an alkylpalladium(II) intermediate. When applied to 1-naphthyl triflate-tethered vinylalanes, the same reaction conditions mediate stereospecific 1,2-diarylation, leading to 2,3,3a,4-tetrahydro-1H-cyclopenta[def]phenanthrenes in excellent yields. The influence of DABCO, tether length and solvent polarity was studied. Selective tandem arylation/1,2-methyl migration could also be achieved in non-polar solvent in absence of Lewis base. While steric properties took precedence over electronic considerations when inducing product selection, preagostic C-H···Pd interactions were postulated to facilitate 1,3-metal migration in the production of 1H-cyclopenta[def]phenanthrene derivatives.

Investigation of the catalytic formation, reactivity and synthetic scope of sp³-gem-organodimetallic palladio(II)/main group metal (main group metal = tributylstannyl, dialkylalumino) alkane species has been carried out. Insight was expanded regarding the inter- and intramolecular reactivity of vinylmetallic reagents in presence of transition metal catalysts. New Pd-catalysed methodologies for carbon-carbon bond formation were developed, such as cyclopropanation of strained olefins, as well as tandem vinylalane arylation/1,2-methyl transfer and 1,2-diarylation. On the one hand, geminal π-allylpalladio(II)/tributylstannylalkane intermediates are produced by oxidative addition of Pd(0) catalysts to α-tributylstannylpropenyl acetate derivatives. They adopt ambiphilic behaviour depending on the transition metal pre-catalyst, presence or absence of phosphine ligands, and reaction temperature. In presence of tetrakis(triphenylphosphine)palladium(0) with additional bidentate ligand, the carbenoid reactivity of these gem-organobismetallic species is exposed by reaction with dimethyl malonate. Deuterium-labeling studies demonstrated sequential functionalisation of the C-Sn and C-Pd bonds. Conversely, phosphine-free catalyst bis(dibenzylideneacetone)palladium(0) uncovers metal-carbene reactivity, and dimerisation and strained alkene cyclopropanation reactions are observed. The nature of the palladium catalyst controls the reactivity of the carbenoid species. Finally, bis(cyclooctadienerhodium(I) chloride) catalytically activates the alkenylstannane moiety, leaving the allylic acetate leaving group available for further transformations. On the other hand, gem-disubstituted trifluoromethanesulfonyloxy- and iodopalladio(II)/ dialkylaluminoneopentane species are generated by intramolecular migratory insertion of 2,2-disubstituted-1-butenyldialkylalanes with σ-arylpalladium(II) triflate and iodide intermediates. Using excess Lewis-basic 1,4-diazabicyclo[2.2.2]octane, electron-rich tris(para-methoxyphenyl)phosphine ligand and acetonitrile as solvent, tandem arylation/1,2-alkyl migration from aluminum to carbon affords 7-substituted-1-ethyl-1-methylindanes containing an all-carbon quaternary stereogenic centre in good yields. This reaction is tolerant of 6-aryl methyl ethers, thioethers and trimethylsilanes. Deuterium labeling established that protiodealumination of the key neopentyl(methyl)aluminum triflate intermediate is caused by the acetonitrile solvent. The organodimetallic species in that study were shown to be configurationally stable, hence the stereospecificity of the process that proceeds via carbopalladation, transmetalation and reductive elimination of an alkylpalladium(II) intermediate. When applied to 1-naphthyl triflate-tethered vinylalanes, the same reaction conditions mediate stereospecific 1,2-diarylation, leading to 2,3,3a,4-tetrahydro-1H-cyclopenta[def]phenanthrenes in excellent yields. The influence of DABCO, tether length and solvent polarity was studied. Selective tandem arylation/1,2-methyl migration could also be achieved in non-polar solvent in absence of Lewis base. While steric properties took precedence over electronic considerations when inducing product selection, preagostic C-H···Pd interactions were postulated to facilitate 1,3-metal migration in the production of 1H-cyclopenta[def]phenanthrene derivatives.

<p>Moisture can significantly affect flexible pavement performance. As such, it is crucial to remove moisture as quickly as possible from the pavements, mainly to avoid allowing moisture into the pavement subgrade. In the 1990s the Indiana Department of Transportation (INDOT) adopted an asphalt pavement drainage system consisting of an open-graded asphalt drainage layer connected to edge drains and collector pipes to remove moisture from the pavement system.</p> <p>Over the intervening two decades, asphalt pavement materials and designs have dramatically changed in Indiana, and the effectiveness of the pavements drainage system may have changed. Additionally, there are challenges involved in producing and placing open-graded asphalt drainage layers. They can potentially increase costs, and they tend to have lower strength than traditional dense-graded asphalt pavement layers. </p> <p>Given the potential difficulties, the overall objective of this research was to evaluate the effectiveness of the INDOT’s current flexible pavement drainage systems given the changes to pavement cross-sections and materials that have occurred since the open-graded drainage layer was adopted. Additionally, the effectiveness of the filter layer and edge drains were examined.</p><p><br>Laboratory experiments were performed to obtain the hydraulic properties of field-produced asphalt mixture specimens meeting INDOT’s current specifications. The results were used in finite element modeling of moisture flow through pavement sections. Modeling was also performed to investigate the rutting performance of the drainage layers under various traffic loads and subgrade moisture conditions in combination with typical Indiana subgrade soils. The modeling results were used to develop a design tool that can assist the pavement designer in more accurately assessing the need for pavement drainage systems in flexible pavements.<br></p>

L’objectif de ce travail étaient le développement de catalyseurs hétérogènes efficaces pour promouvoir des réactions asymétriques, en utilisant la polymérisation oxydante ou la formation de polymères de coordination. De nouveaux complexes de salen Co(III) chiraux modifiés par des groupements aromatiques sur les position 5, 5’ ont été préparés et testés dans le dédoublement cinétique hydrolytique (HKR) des époxydes terminaux en conditions homogènes. Ces complexes ont été ensuite engagés dans les polymérisations oxydantes électrochimiques ou chimiques, et une stratégie de copolymérisation a fourni des polymères chiraux très efficaces et stables pour catalyser l’HKR dans des conditions hétérogènes. Nous avons alors cherché à préparer un catalyseur capable de catalyser deux réactions en cascade, en copolymérisant deux complexes de salen portant des métaux différents. Pendant ces études, les complexes de salen Mn ont révélé leur participation active à la réaction d’HKR des époxydes terminaux catalysée par les complexes de salen Co(III), en augmentant l’excès énantiomérique du produit de façon significative. Les études mécanistiques ont été ensuite réalisées pour tenter de comprendre le rôle des complexes de Mn dans cette réaction. De plus, des complexes de salen fonctionnalisés par le groupement pyridine ou le groupement de type acide isophtalique ont été synthétisés. Ces complexes ont été utilisés pour préparer de nouveaux réseaux de polymères de coordination poreux chiraux (collaboration avec l’équipe LCI de l’ICMMO et l’Institut Lavoisier à Versailles), qui sont ensuite testés comme catalyseurs hétérogènes dans la réaction de Henry asymétrique et la réaction d’HKR. / The aim of this work was to prepare new chiral heterogeneous catalysts for asymmetric catalysis by oxidative polymerization of chiral organometallic complexes or by formation of chiral metal organic frameworks. New chiral salen Co(III) complexes modified by oxidizable aromatic groups at position 5,5’ have been prepared and tested as homogeneous catalysts in the Hydrolytic Kinetic Resolution (HKR) of terminal epoxides. These complexes have also been engaged into the oxidative electrochemical and chemical polymerization, and a copolymerization strategy has afforded very efficient and stable heterogeneous catalysts for the HKR. The idea of copolymerization has then been extended to the copolymerization of two salen complexes with different metals, which is expected to promote successively two different asymmetric transformations. During preliminary investigations, the salen Mn complexes have been found to be able to enhance the catalytic performance of salen Co(III) complexes in the HKR by increasing significantly the enantiomeric excess of the products. Mechanistic studies have thus been realized to understand the role of salen Mn complexes in this reaction. Besides, some chiral salen complexes functionalized by pyridine or isophtalic acid groups have been synthesized for the preparation of new chiral metal organic frameworks (collaboration with LCI of ICMMO and Institut Lavoisier of Versailles), which have also been tested in the asymmetric Henry reaction and the HKR as heterogeneous catalysts.

Formaldehyde is a chemical used widely in the manufacture of building materials. A remarkable example is represented by the Lucite two-step Alpha technology for the large scale production of methyl methacrylate (MMA), the essential building block of all acrylic-based products. Esters and ketones are important intermediates in the manufacture of acrylate esters therefore α-hydroxymethylenation of carbonyl compounds using formaldehyde as a one carbon alkylating agent and subsequent dehydration to the corresponding methylenated derivatives has been explored in the current work. We report a novel catalytic approach for the synthesis of methyl methacrylate (MMA) via one-pot α-methylenation of methyl propanoate (a chemical intermediate of the ALPHA process) with formaldehyde, generated in situ by Ru-catalysed dehydrogenation of methanol. Elucidation of the mechanism involved in the catalytic dehydrogenation of methanol along with the collateral alcohol decarbonylation reaction was gained through a combined experimental and DFT study. The development of an alternative process where anhydrous formaldehyde is produced in situ would provide a simplification over the current second step of the ALPHA technology where the formaldehyde is initially produced as formalin, subsequently dehydrated to afford anhydrous formaldehyde in order to ensure high selectivity to MMA. As an alternative approach, ketones, in particular 3-pentanone and 2-butanone, were targeted as potential substrates in order to overcome some of the problems related to competing reactions that occur at the ester group. Hydroxymethylenation, followed by dehydration and Baeyer-Villager oxidation, possibly catalysed by enzymes to reverse the normal selectivity, leads to the formation of acrylate esters. The catalytic reaction is enabled by a gold carbene hydroxide complex in such a way that the substrate undergoes C-H activation and the nascent metal alkyl acts as a nucleophile towards the electrophilic formaldehyde, supplied in the form of alcoform* (solution of paraformaldehyde in methanol).