No / Phosphonium tosylates have been investigated as solvents for the Diels¿Alder reactions of isoprene with methyl acrylate, but-3-en-2-one and acrylonitrile. The reactions with oxygen-containing dienophiles showed high regioselectivity. Graphic

Yes / A range of twelve stabilised phosphonium ylides containing tetrahydrofuran, tetrahydropyran or 2,2- dimethyl-1,3-dioxolane rings have been prepared and fully characterised, including one X-ray structure determination of each type. The X-ray structures confirm the PvC and CvO functions to be syn and all the compounds undergo thermal extrusion of Ph3PO to give the corresponding alkynes. In some cases there is also competing loss of Ph3P to give different carbene-derived products and evidence has been obtained for the generation of 2-phenyloxete in this way. Raising the pyrolysis temperature leads in several cases to new secondary reactions of the alkyne products involving a sequence of alkyne to vinylidene isomerisation, intramolecular CH insertion, and retro Diels Alder reaction.

Les travaux réalisés au cours de cette thèse sont centrés sur la synthèse et la réactivité de ligands phosphorés à caractère faiblement s-donneur et fortement p-accepteur. Il s'agit de ligands phosphines présentant une charge cationique en position a de l'atome de phosphore. Cette charge positive est amenée alternativement par un fragment amidinium ou bien cyclopropénium, conduisant respectivement aux amidinio- et cyclopropéniophosphines. Ces travaux sont présentés en trois chapitres. Dans le premier chapitre, après un partie bibliographique, nous avons décrit la synthèse de di-imidazolo- et di-imidazoliophosphines diversement P-substituées par des groupements aryle, alkyle et di(alkyl)amino. L'étude de la réactivité de ces ligands vis-à-vis d'acides de Lewis métalliques ou non a permis de démontrer que la nature du substituant porté par l'atome de phosphore influençait de façon critique les propriétés de coordination. Divers complexes métalliques et oxydes de phosphines ont été ainsi obtenus et entièrement caractérisés. Dans le deuxième chapitre, nous nous sommes intéressés à la préparation de phosphines a-cationiques chirales. Deux cas distincts ont été ainsi considérés : des phosphines cationiques à chiralité électrostatique dans lesquelles l'effet électrostatique prime sur l'effet stérique et des phosphines cationiques à chiralité stérique dans lesquelles l'effet stérique est cette fois-ci prédominant. Il a été démontré qu'en dépit des effets électroniques et stériques présents, ces phosphines étaient capables de se coordiner à un centre métallique. Divers complexes de métaux de transition de ces phosphines P-chirogènes ont été ainsi préparés et entièrement caractérisés. Dans le cas des phosphines à chiralité électrostatique, une version énantiopure a été isolée grâce à l'utilisation d'un complexe de palladium(II) orthométallé optiquement actif comme agent de dédoublement. Le troisième chapitre est axé sur le développement de ligands carbonés anioniques fortement donneurs de type imidazolyle et de leurs complexes. Afin de contre-balancer l'extrémité carbonée donneuse, une partie phosphorée acceptrice de type imidazolophosphine a été introduite. En série rhodium(I), deux complexes de ces ligands chélatants hybrides phospho-carbonés ont été ainsi isolés et caractérisés. / The project developed during this PhD thesis aims at the synthesis and reactivity of phosphorus ligands with weak s-donor and strong p-acceptor properties. They correspond to phosphine ligands featuring a cationic charge in a position of the phosphorus atom. The cationic charge can be introduced alternatively through an amidinium or a cyclopropenium moiety affording amidinio- and cyclopropeniophosphines, respectively. In the first chapter, after a bibliographical section, the synthesis of di-imidazolo- and di-imidazoliophosphines with aryl, alkyl and dialkylamino P-substituents is described. The study of the reactivity of these phosphine ligands towards metallic (or not) Lewis acids demonstrates that the nature of the P-substituent influences dramatically the corresponding coordination properties. Various cationic metal complexes and phosphine oxides are obtained and fully characterized. The second chapter of the thesis is focused on the development of chiral a-cationic phosphines. Two different cases are considered: cationic phosphines with electrostatic chirality where steric effects may be neglected and cationic phosphines with predominant steric chirality. In both cases, despite electron-poor character, these phosphines were shown to coordinate various transition metal centers. In the case of phosphines featuring electrostatic chirality, a representative was isolated in an optically pure form through the use of chiral orthometallated palladium(II) complexes as resolving agents. Finally, the third chapter concerns the development of imidazolyl carbon ligands and the corresponding complexes. In order to balance the electron-richness of the anionic imidazolyl donor extremity, an electron-poor phosphorus coordinating end, namely an imidazolophosphine is introduced. In the rhodium(I) series, two chelating complexes of these hybrid 'rich-poor' carbon-phosphorus ligands have been isolated and characterized.

Un récent rapport de l’OMS met en garde les autorités de santé sur l’émergence de résistances chez les bactéries et le développement de souches bactériennes multi-résistantes aux traitements antibiotiques actuels. La progression de ces phénomènes est dû à différents facteurs. L’environnement hospitalier concentre un usage important de traitements antibiotiques et représente ainsi un terreau favorable au développement de résistances chez les bactéries. Le staphylocoque doré, ainsi que sa souche résistante (SARM), s’avèrent problématiques et entraînent un grand nombre de maladies nosocomiales. Dans ce contexte, il est primordial de mettre au point de nouveaux agents antibactériens permettant de lutter contre ces bactéries. Les liquides ioniques (sels à point de fusion bas) démontrent d’importantes propriétés antibactériennes. Néanmoins les mécanismes de cet effet bactéricide n’ont pas encore été établis. Ainsi nous nous proposons, dans un premier temps, de synthétiser des liquides ioniques di-cationiques afin d’étudier les différents facteurs structuraux qui régissent leur activité antibactérienne. Dans un second temps, nous concevrons des liquides ioniques à base de phosphoniums fonctionnalisés avec une sonde fluorescente. En exploitant les propriétés spectroscopiques, nous tenterons d’observer leurs interactions avec les cellules bactériennes. Enfin, nous nous proposons d'utiliser les phosphoniums comme agents de fonctionnalisation de surface dans le but de mettre au point des surfaces aux qualités bactéricides intrinsèques. Pour ce faire nous utiliserons différentes méthodes comme la conception de monocouches auto-assemblées ou l’électropolymérisation. / A recent WHO report warns the health authorities about the emergence of new bacterial resistances and the development of multi-resistant strains against current antibiotics treatments. The growth of those resistances is due to several factors. The hospital environment concentrates a significant use of antibiotics and disinfectant representing a favorable ground for bacterial resistance development. Among them the Staphylococcus aureus and its methicillin resistant strain (MRSA) represent a crucial issue in care environments and is a major cause of hospital acquired infections. In this context, it is essential to develop new antibacterial agents to fight against these bacteria. Ionic liquid are low melting point salts, they show significant antibacterial properties. However, the fact that the mechanisms of action of their bactericidal effect have not been established yet constitutes a major obstacle to their development as bactericidal agents. Thus, we propose to synthetize ammonium- and phosphonium-based di-cationic ionic liquids in order to study the different structural factors that govern their antibacterial activity. Then we will develop phosphonium based ionic liquids functionalized with a fluorescent probe. By taking advantage of their spectroscopic properties we will try to observe their interactions with bacterial cells. Finally, we propose to use the phosphonium salts as surface functionalization agents in order to design surfaces with intrinsic antibacterial properties. To do so, we will use innovative methods such as conception of self-assembled monolayers or electropolymerization technics.

The clean reaction of 5-lithio-6-diisopropylphosphinoacenaphthene (1') with dichlorophosphines, RPCl₂ (R = Ph, Fc, NMe₂, iPr), led to the formation of peri-substituted phosphino-phosphonium chloride salts 2-5. The synthetic utility of these salts was demonstrated in a range of reactions. Mixed tertiary/secondary bis(phosphines) (6 and 7) were prepared by the LiAlH₄ reduction of phenyl or ferrocenyl phosphino-phosphoniums (2 and 3), and the bis(borane) adduct of 6 was prepared by reduction of 2 with BH₃•SMe₂. Reaction of 2 and 3 with a large excess of MeOTf at elevated temperature gave 1,2-diphosphoniums (11 and 12), which were subjected to reduction and co-ordination to a molybdenum(0) centre. An investigation into the co-ordination chemistry of 2 revealed three distinct modes of reactivity. In the reaction with [(nor)Mo(CO)₄] the Mo(0) complex [(2)Mo(CO)₄Cl] (18) was isolated, in which monodentate co-ordination was observed. [PtCl₂(cod)] reacts with the chloride and triflate salts of 2 to form [(2Cl)PtCl₂] (19) and [((2Cl)PtCl)₂][TfO]₂ (21) respectively, both of which show co-ordination of 2 as a bidentate phosphine/chlorophosphine ligand. A palladium(II) dimer (22) in which 2 forms a chelating phosphine/phosphide ligand was isolated from the oxidative addition of 2 to a palladium(0) complex. The geminally bis(peri-substituted) tridentate phosphine (27) was prepared by reaction of 1' with half an equivalent of iPrPCl₂. 27 has a rather strained geometry, and displays restricted dynamics on an NMR timescale, which leads to anisochronicity of all three phosphorus nuclei at low temperatures. Strained bis and tris(sulfides) 28 and 29 and the bis(selenide) 30 have been isolated from the reaction of 27 with sulfur and selenium, respectively. A series of co-ordination complexes, [(27)Cu(MeCN)][BF₄] (32), [(27)PtCl][Cl] (33), [(27)FeCl₂] (34) and fac-[(27)Mo(CO)₃] (35), with tetrahedral, square planar, trigonal bipyramidal and octahedral geometries, respectively, were synthesised. In all of these complexes the tris(phosphine) backbone is distorted, but to a significantly smaller extent that in the chalcogenides 28-30.

The use of ionic liquids (ILs) as both reagents and solvents is widely recognised. ILs offer a number of advantages compared to regular molecular solvents. These advantages include: chemical and thermal stability, no measurable vapour pressure, no or lower toxicity, non-flammability, catalytic ability, high polarity and they can be recycled. There are a number of research groups investigating the various applications of this reaction medium and most studies have focused on solvents derived from the imidazolium cation. The use of the imidazolium-based ILs in the Diels-Alder reaction has been studied in detail and higher yields compared to conventional methods have been reported. The IL affects the rate and interesting selectivities have been observed. However, not much attention has been paid to the scope and limitations of phosphonium ILs (PILs). Therefore the focus of this thesis is the synthesis and application of novel chiral PILs as environmentally benign, task-specific solvents for the Diels-Alder reaction. In addition, this research seeks alternative ways to eliminate the use of toxic heavy metal catalysts and to exploit methodologies which reduce the energy consumption of the Diels-Alder reaction. A series of CILs were synthesised from the chiral pool and they were characterised by thermogravimetric analysis, differential scanning calorimetry and spectroscopy. They were then investigated as solvents and catalysts in the Diels-Alder reactions of a series of dienes (cyclopentadiene, isoprene, 2,3-dimethylbuta-1,3-diene, furan, pyrrole, N-methyl pyrrole) and dienophiles (methyl acrylate, methyl vinyl ketone, acrylonitrile, dimethyl maleate, acrolein, dimethylacetylene dicarboxylate, maleic anhydride and maleimide). Investigation of the effect of PILs in the presence of three heterogeneous catalysts Al2O3, SiO2 and K-10 montmorillonite were studied. Ultrasound and microwave-assisted Diels-Alder reactions in the PILs, in the absence and presence of the catalysts, were also studied. The reactions of these prototypical substrates illustrated that the solvents are indeed task-specific.

Hemisynthèse stéréosélective d’acides aminés hétérosubstitués sur la chaîne latérale.Applications au radio-fluoromarquage pour l’imagerie de peptides.Ce travail de thèse, qui a été réalisé à l’Institut de Chimie Moléculaire de l’Université de Bourgogne et en collaboration avec l’Institut de Neuroscience Cognitives et Intégrative d’Aquitaine, porte sur la mise au point de nouvelles méthodes de synthèse d’acides aminés hétérosubstitués sur la chaine latérale par des groupements phosphorés ou silylés, ainsi que sur leurs applications. Dans une première partie, la synthèse d’acides aminés silylés sur la chaine latérale est réalisée sans racémisation par réaction de Wittig entre un sel de phosphonium, dérivé d’acide L-aspartique, avec un aldéhyde aromatique porteur du groupement silylé. Ces acides aminés ont été utilisés en synthèse peptidique pour donner des di- et tripeptides silylés par réaction avec des dérivés d’alanine et de phénylalanine. Il a été montré que les acides aminés et peptides silylés pouvaient être fluorés par réaction avec des fluorures, et que dans le cas de dérivés di-t-butylsilylés, les composés fluorés obtenus se révèlent d’une très grande stabilité à pH physiologique. L’étude de la fluoration des peptides di-t-butylsilylés par K18F/K222 a permis d’obtenir les dérivés radiomarqués avec des rendements radiochimiques et des activités molaires atteignant respectivement 39% et 410 GBq.mmol-1. Dans la seconde partie, la synthèse d’acides aminés et peptides hétérosubstitués ou fonctionnalisés sur la chaine latérale, a été mise au point. Le principe de cette synthèse repose sur une cycloaddition [3+2] entre un acide aminé porteur d’un groupement azido avec un alcyne disubstitué. Alors que la réaction par catalyse avec un sel de cuivre ou un complexe de ruthénium ne conduit pas aux produits recherchés, la cycloaddition a été mise au point sous microondes en utilisant le glycérol comme solvant. Dans ces conditions, 13 nouveaux acides aminés porteurs d’un noyau triazole en position γ, et des substituants silylés, phosphorés, amines, amides …ont été préparés sans racémisation et ce avec des rendements atteignant 89%. Les méthodologies mises au point dans ce travail de thèse offrent de nouvelles voies pour la synthèse de dérivés acides aminés silylés ou phosphorés utiles pour la chimie de coordination, la catalyse asymétrique et pour le radiomarquage par les ions fluorure 18F-.Mots clés : Phosphoniums, acides aminés, silanes ; [18F]-radiofluoration, triazoles. / Stereoselective hemisynthesis of lateral chain heterosubstituted aminoacids.Applications on radiofluorolabeling for peptide imaging.This thesis work, which was carried out at the Institute of Molecular Chemistry of the University of Burgundy and in collaboration with the Institute of Cognitive and Integrative Neurosciences of Aquitaine, focuses on the development of new methods for the synthesis of side chain heterosubstituted amino acids including phosphine containing or silyl groups, as well as on their applications. In a first part, the synthesis of side chain silylated amino acids is achieved without racemization using a key Wittig reaction between a phosphonium salt, derived from L-aspartic acid, and an aromatic aldehyde bearing the silyl group. These aminoacids have been used in peptide synthesis to give silylated di- and tripeptides by reaction with alanine and phenylalanine derivatives. It has been shown that the silylated aminoacids and peptides can be fluorinated by reaction with fluorides, and that in the case of di-t-butylsilyl derivatives, the fluorinated compounds obtained are found to be very stable at physiological pH. The study of the fluorination of di-t-butylsilyl peptides by K18F / K222 allowed to obtain radiolabelled derivatives with radiochemical yields and molar activities reaching 39% and 410 GBq.mol-1, respectively. In the second part, the synthesis of aminoacids and peptides heterosubstituted or functionalized on the side chain, was developed. The principle of this synthesis is based on a [3 + 2] cycloaddition between an aminoacid bearing an azido group with disubstituted alkyne. While the reaction catalyzed using a copper salt or a ruthenium complex does not lead to the desired products, the cycloaddition was developed under microwave irradiation using glycerol as a solvent. Under these conditions, 13 new amino acids carrying a triazole ring at the γ position, and bearing silyles, phosphines, amines, amides.. substituents were prepared without racemization and with yields up to 89%. The methodologies developed in this thesis offer new efficient ways for the synthesis of silyl or phosphorus amino acid derivatives, useful for coordination chemistry, asymmetric catalysis and radiolabeling by the fluoride ion18F-.Key words: Phosphoniums, aminoacids, silanes, [18F]-radiofluorination, triazoles

In this work, ionic liquids (ILs) were investigated for use as battery electrolytes. The ILs were synthesized from quaternary ammonium and phosphonium salts and TFSI-. A dendrite free lithium metal anode was demonstrated by deposition of a lithium-potassium alloy. Several phosphonium ILs were synthesized using the TFSI- and PF6- anions until a room temperature IL was obtained. The smaller size, highly symmetric PF6- anion yielded high melting point salts, while TFSI- yielded much lower melting point ILs. When a room temperature IL, Bu3HexP+TFSI-, was obtained the analogous ammonium IL, Bu3HexP+TFSI-, was synthesized and compared. The phosphonium-based ionic liquid showed improved stability and physical properties compared to the analogous ammonium-based IL. The phosphonium-based IL had higher conductivity, 0.43 mS/cm, than the ammonium-based IL, 0.28 mS/cm. The addition of LiTFSI to both ILs led to a decrease in conductivity and increase in viscosity. The lower viscosity and higher stability of the phosphonium-based IL led to higher current density and stability for electrodeposited lithium metal. IL reduction interfered with lithium deposition reflecting lower coulombic efficiencies and giving the appearance of an unstable lithium couple. An optimum deposition potential was found which was bounded by the electrochemical stability of each IL. The stability of lithium in the ILs increased at lower temperature due to slower reactivity with the IL. Addition of higher quantities of lithium ions caused a higher fraction of the cathodic current going to lithium deposition that was reoxidized. The stability of lithium in the ILs increased at lower temperature due to slower reactivity with the IL. The electrodeposition and reoxidation of potassium was also demonstrated. Deposition of a lithium-potassium alloy caused slight increases in the cathodic and anodic currents along with higher coulombic efficiencies. Also, it was found that a lithium-potassium alloy could be deposited at high current for long times without the occurrence of dendrites.

La synthèse et caractérisation de deux nouveaux liquides ioniques à base de cholinium nommés N-(2-hydroxyethyl)-N, N-dimethyl-N-octylammonium bis(trifluoromethanesulfonyl)imide [C8linChol]+[NTf2]- et N-(2-hydroxyethyl)-N-(2-ethylhexyl)-N, N-dimethyl ammonium bis(trifluoromethanesulfonyl)imide [C8ramChol]+[NTf2]- ont été synthétisés et caractérisés par 1H NMR, 13C NMR, ATR-FTIR et ESI-MS. Les propriétés thermodynamiques comme l’énergie d’activation pour le flot visqueux, le volume molaire et l’entropie molaire ont été déduits de mesures de la masse volumique et de la viscosité. Ces calculs ont montré que les liquides ioniques possédant des chaînes alkyles ramifiées sont plus ordonnés que ceux qui ont des chaînes alkyles linéaires. L’étude des propriétés d’extraction du liquide ionique ramifié et du liquide ionique linéaire montre qu’ils sont capables d’extraire respectivement 98,6% et 40,5% d’Ag(I) à pH 5. L’extraction d’Ag(I) avec un liquide ionique dérivé du phosphonium (2,4,4 dimethyl(penthyl) phosphinate de trihexyl (tetradecyl) phosphonium a également été étudié. Cette étude montre en particulier que 80 à 85% de l’Ag(I) pet être extrait à un Ph 3 par ce liquide ionique dilué dans un kérosène modifié ou non par du decan-1-ol. La spectroscopie infrarouge montre que l’extraction provient probablement de l’anion protonné du liquide ionique. / Synthesis and characterization of two new cholinium-based ionic liquids, named N-(2-hidroxyethyl)-N,N-dimethyl-N-octylammonium bis(trifluoromethanesulfonyl)imide [C8linCol]+[NTf2]- and N-(2-hidroxyethyl)-N-(2-ethylhexyl)-N,N-dimethyl-ammonium bis(trifluoromethanesulfonyl)imide [C8ramCol]+[NTf2]- has been developed by 1H NMR, 13C NMR, ATR-FTIR y ESI-MS. Properties as the viscous flux activation energy, the volume or the molar entropy have been calculated from the experimental data on density and viscosity. Calculations showed that the ramified ionic liquid possess a higher degree of structural order when compared with the linear ionic liquid. Also, their capacity for the recovery of Ag (I) was determined and an extraction level of 98.6% for the linear and 40.5% for the ramified ionic liquid was found. Maximum extraction was found at pH 5.0 with an important selectivity on the extraction of Ag (I) and Cu (II) towards Fe (III). Ag (I) extraction with a phosphonium-based ionic liquid (2,4,4 dimethyl(penthyl) phosphinate de trihexyl(tetradecyl) phosphonium) was also tested. Extraction tests were developed at different concentration values when dissolved in kerosene or kerosene plus decan-1-ol. An extraction level of 80 to 85% was determined with the different mixtures at a maximum recovery pH of 3.0. Spectroscopic characterization (ATR-IR) showed the protonation of the anion in the ionic liquid forming the acid specie. This specie is probably the responsible for the extraction of silver. The formation of a dimeric specie was found in the 31P NMR and the value of the formation constant was calculated.

Charge transport and structural dynamics in a homologous pair of ammonium and phosphonium based room temperature ionic liquids (ILs) have been characterized over a wide temperature range using broadband dielectric spectroscopy and quasi-elastic light scattering spectroscopy. We have found that the ionic conductivity of the phosphonium based IL is significantly enhanced relative to the ammonium homolog, and this increase is primarily a result of a lower glass transition temperature and higher ion mobility. Additionally, these ILs exhibit pronounced secondary relaxations which are strongly influenced by the atomic identity of the cation charge center. While the secondary relaxation in the phosphonium IL has the expected Arrhenius temperature dependence characteristic of local beta relaxations, the corresponding relaxation process in the ammonium IL was found to exhibit a mildly non-Arrhenius temperature dependence in the measured temperature range—indicative of molecular cooperativity. These differences in both local and long-range molecular dynamics are a direct reflection of the subtly different inter-ionic interactions and mesoscale structures found in these homologous ILs.