Para a síntese de um dos quatro possíveis estereoisômeros do ácido 3-(4- clorofenil)piroglutâmico, precursor da forma mais ativa do fármaco Baclofen, foram investigadas duas metodologias alternativas, cujas etapas principais eram, respectivamente, (i) a reação de Michael entre o N-acetamidomalonato de dietila ou de dibenzila com o 4-clorotiocinamato de metila ou fenila, na ausência de solvente e na presença de catalisadores de transferência de fase enantioméricamente puros, e (ii) a reação de Michael entre complexos de níquel (quirais ou aquirais), derivados da glicina, com a (5S)-N-(E-4-clorocinamoil)-5-metoxicarbonil-2-pirrolidinona. A primeira destas metodologias não conduziu a bons resultados, mas a investigação das causas da baixa estereosseletividade, observada para reações empregando tanto tiolésteres como chalcona, permitiu a proposição de um novo modelo de interação catalisador/doador/aceptor, em que o doador é o N-acetamidomalonato de dibenzila e o aceptor é a chalcona. Quanto às adições de Michael dos complexos de níquel, empregados como equivalentes nucleofílicos da glicina, as reações foram bem sucedidas. O par aceptor/doador que se mostrou mais adequado foi aquele composto pelo complexo de níquel, derivado da (L)-prolina, e pela (5S)-N-(E-4- clorocinamoil)-5-metoxicarbonil-2-pirrolidinona. Neste caso, o ácido (2R,3S)-3-(4- clorofenil)piroglutâmico foi obtido em rendimento global de 46%. Este resultado permite prever que, pelo emprego do mesmo aceptor, mas de estereoquímica absoluta contrária, é possível preparar o precursor do (R)- baclofen, que é o enantiômero mais ativo do fármaco em questão. / Two alternative methodologies were investigated aiming the synthesis of one of the four stereoisomers of the 3-(4-chlorophenyl)pyroglutamic acid, as a precursor of Baclofen, a drug used for the treatment of some neurological diseases. The key step for the first one was the asymmetric Michael addition of diethyl or dibenzil N- acetamidomalonate to methyl or phenyl 4-chlorotiocinnamate, in the absence of solvent, and employing enatiomerically pure phase transfer catalysts. A low degree of enantioselectivity was observed for all addition reactions of dibenzil N- acetamidomalonate to tiolesters or chalcone as Michael acceptors. The investigation of the origin of such lack of stereoselectivity allowed the proposal of a model for the diastereomeric transition states of the Michael addition of dibenzil N- acetamidomalonate to chalcone. As for the second synthetic methodology, the asymmetry generating step would be the Michael addition of glycine derived chiral or achiral nickel complexes to (5S)-N-(E-4-clorocinnamoil)-5-methoxycarbonyl-2- pirrolidinone. Best results were obtained for the Michael addition of a nickel complex, bearing (S)-2-[N-(N\'-benzylprolyl)amino]benzophenone as ligand , to (5S)-N-(E-4- clorocinnamoil)-5-methoxycarbonyl-2-pirrolidinone.Such reaction afforded the expected (S)-3-(4-chlorophenyl)pyroglutamic acid, in 46% yield. Such result can be extrapolated to the synthesis of the (R)-configured analog, precursor of the more active stereoisomer of Baclofen.

Neste trabalho, foi proposta a preparação e redução, seguida de hidrólise oxidativa, de alguns derivados imínicos da 2-metilsulfinil-2-metilsufanil-1-tetralona e da 2-metilsulfinil-2-metilsulfanil-1-indanona. A 2-metilsulfinil-O-metil-oxima da 1-tetralona foi preparada pela oxidação da 2-metilsulfanil-O-metil-oxima. O sulfóxido assim obtido pôde ser sulfanilado empregando-se terc-butil lítio e metanotiolsulfonato de metila, resultando um único diastereoisômero que se mostrou inerte na reação de redução da função imínica com NaBH4. Tentativas de preparar a N-tosil-imina da 2-metilsulfinil-1-tetralona, por oxidação do sulfeto correspondente, não conduziram ao produto esperado, mas sim à enamina. Buscando uma rota alternativa para a preparação de derivados imínicos de sulfinil ciclanonas sulfaniladas, foram preparados β-cetossulfóxidos derivados da 1-tetralona e da 1-indanona que, após serem sulfanilados, seriam submetidos às reações com aminas aromáticas ou alifáticas. As reações de sulfanilação da 2-metilsulfinil-1-indanona e da 2-metilsulfinil-1-tetralona foram efetuadas em condições de transferência de fase, na presença dos catalisadores TEBAC ou QUIBEC. Para ambos os casos, os rendimentos de produto foram cerca de 80 %. Enquanto os dois catalisadores conduziram a resultados estereoquímicos similares para a sulfanilação da 2-metilsulfinil-1-indanona, para a 2-metilsulfinil-1-tetralona, o uso do catalisador quiral QUIBEC resultou em um aumento da diastereosseletividade da reação, no sentido da formação do diastereoisômero majoritário de configuração relativa CR,SR. Foram também efetuadas as reações de sulfanilação das duas 2-metilsulfinil ciclanonas em meio homogêneo, empregando como bases o hidróxido de lítio ou o di-isopropil amideto de magnésio. Porém, as reações das sulfinil ciclanonas sulfaniladas assim preparadas com a anilina e com a metil-amina não foram bem sucedidas. As reações de redução com boroidreto de sódio das duas sulfinil ciclanonas sulfaniladas conduziram aos respectivos álcoois em cerca de 70 % de rendimento e na forma de um único diastereoisômero, de configuração relativa SR,C-1R,C-2R, no caso do tetralol. As duas metilsulfinil ciclanonas sulfaniladas, opticamente ativas, foram preparadas em bons rendimentos, mas sob forma escalêmica, o que não permitiu o prosseguimento do estudo do curso estereoquímico da redução da carbonila de tais compostos. A reação de adição do enolato de lítio do acetato de etila à 2-metilsulfinil-2-metilsulfanil-1-indanona conduziu ao produto esperado em bom rendimento, mas com baixo excesso diastereoisomérico. Em condições análogas, a 2-metilsulfinil-2-metilsulfanil-1-tetralona mostrou-se inerte. / The original proposal of this research work was to prepare imines of 2-methylsulfinyl-2-methylsulfanyl-1-tetralone and 2-methylsulfinyl-2-methylsulfanyl-1-indanone that would be subsequently reduced and submitted to oxidative hydrolysis. By oxidation of 2-methylsulfanyl-1-tetralone-O-methyloxime the corresponding sulfoxide could be prepared, and submitted to the sulfanylation reaction using tert-butyllittium/methyl methanethiolsulfonate. The resulting product was obtained as a single diastereoisomer but showed to be unreactive towards reduction using sodium borohydride In attempting to convert the 2-methylsulfanyl-1-tetralone into the corresponding sulfoxide by oxidation, the corresponding sulfinylenamine was obtained instead of the expected sulfinylimine. Searching for an alternative synthetic route to the desired imines, the required β-ketosulfoxides were prepared and sulfanylated under phase-transfer catalysis using TEBAC or QUIBEC, as catalysts. In both cases, product yield was ca. 80%. Although for the sulfanylation of 2-methylsulfinyl-1-indanone using either TEBAC or QUIBEC the same diastereoselectivity was observed, for the reaction performed with 2-methylsulfinyl-1-tetralone and QUIBEC an improved diastereoselectivity was observed, in favour of the CR,SR diastereoisomer. Analogous sulfanylation reactions were performed in homogeneous medium in the presence of lithium hydroxide or magnesium diisopropylamide acting as bases. However, the reactions of the prepared 2-metylsulfinyl-2-methylsulfanyl ciclanones with aniline or methylamine were unsuccessful. The borohydride reduction of the 2-metylsulfinyl-2-methylsulfanyl ciclanones afforded the corresponding diastereoisomerically pure alcohols in ca. 70% yield, bearing, in the case of the tetralol derivative, the SR,C-1R,C-2R relative configuration. The two optically active sulfanylated 2-methylsulfinyl ciclanones could be prepared in good yields but as a scalemic mixture that precluded further studies in order to determine the stereochemical course of the carbonyl reduction. As for the addition reaction of the ethyl acetate lithium enolate to 2-methylsulfinyl-2-methylsulfanyl-1-indanone, the expected adduct was obtained in good yield but with poor diastereoselectivity. Under the same experimental conditions, the 2-methylsulfinyl-2-methylsulfanyl-1-tetralone underwent no reaction.

Neste trabalho, foi proposta a preparação e redução, seguida de hidrólise oxidativa, de alguns derivados imínicos da 2-metilsulfinil-2-metilsufanil-1-tetralona e da 2-metilsulfinil-2-metilsulfanil-1-indanona. A 2-metilsulfinil-O-metil-oxima da 1-tetralona foi preparada pela oxidação da 2-metilsulfanil-O-metil-oxima. O sulfóxido assim obtido pôde ser sulfanilado empregando-se terc-butil lítio e metanotiolsulfonato de metila, resultando um único diastereoisômero que se mostrou inerte na reação de redução da função imínica com NaBH4. Tentativas de preparar a N-tosil-imina da 2-metilsulfinil-1-tetralona, por oxidação do sulfeto correspondente, não conduziram ao produto esperado, mas sim à enamina. Buscando uma rota alternativa para a preparação de derivados imínicos de sulfinil ciclanonas sulfaniladas, foram preparados β-cetossulfóxidos derivados da 1-tetralona e da 1-indanona que, após serem sulfanilados, seriam submetidos às reações com aminas aromáticas ou alifáticas. As reações de sulfanilação da 2-metilsulfinil-1-indanona e da 2-metilsulfinil-1-tetralona foram efetuadas em condições de transferência de fase, na presença dos catalisadores TEBAC ou QUIBEC. Para ambos os casos, os rendimentos de produto foram cerca de 80 %. Enquanto os dois catalisadores conduziram a resultados estereoquímicos similares para a sulfanilação da 2-metilsulfinil-1-indanona, para a 2-metilsulfinil-1-tetralona, o uso do catalisador quiral QUIBEC resultou em um aumento da diastereosseletividade da reação, no sentido da formação do diastereoisômero majoritário de configuração relativa CR,SR. Foram também efetuadas as reações de sulfanilação das duas 2-metilsulfinil ciclanonas em meio homogêneo, empregando como bases o hidróxido de lítio ou o di-isopropil amideto de magnésio. Porém, as reações das sulfinil ciclanonas sulfaniladas assim preparadas com a anilina e com a metil-amina não foram bem sucedidas. As reações de redução com boroidreto de sódio das duas sulfinil ciclanonas sulfaniladas conduziram aos respectivos álcoois em cerca de 70 % de rendimento e na forma de um único diastereoisômero, de configuração relativa SR,C-1R,C-2R, no caso do tetralol. As duas metilsulfinil ciclanonas sulfaniladas, opticamente ativas, foram preparadas em bons rendimentos, mas sob forma escalêmica, o que não permitiu o prosseguimento do estudo do curso estereoquímico da redução da carbonila de tais compostos. A reação de adição do enolato de lítio do acetato de etila à 2-metilsulfinil-2-metilsulfanil-1-indanona conduziu ao produto esperado em bom rendimento, mas com baixo excesso diastereoisomérico. Em condições análogas, a 2-metilsulfinil-2-metilsulfanil-1-tetralona mostrou-se inerte. / The original proposal of this research work was to prepare imines of 2-methylsulfinyl-2-methylsulfanyl-1-tetralone and 2-methylsulfinyl-2-methylsulfanyl-1-indanone that would be subsequently reduced and submitted to oxidative hydrolysis. By oxidation of 2-methylsulfanyl-1-tetralone-O-methyloxime the corresponding sulfoxide could be prepared, and submitted to the sulfanylation reaction using tert-butyllittium/methyl methanethiolsulfonate. The resulting product was obtained as a single diastereoisomer but showed to be unreactive towards reduction using sodium borohydride In attempting to convert the 2-methylsulfanyl-1-tetralone into the corresponding sulfoxide by oxidation, the corresponding sulfinylenamine was obtained instead of the expected sulfinylimine. Searching for an alternative synthetic route to the desired imines, the required β-ketosulfoxides were prepared and sulfanylated under phase-transfer catalysis using TEBAC or QUIBEC, as catalysts. In both cases, product yield was ca. 80%. Although for the sulfanylation of 2-methylsulfinyl-1-indanone using either TEBAC or QUIBEC the same diastereoselectivity was observed, for the reaction performed with 2-methylsulfinyl-1-tetralone and QUIBEC an improved diastereoselectivity was observed, in favour of the CR,SR diastereoisomer. Analogous sulfanylation reactions were performed in homogeneous medium in the presence of lithium hydroxide or magnesium diisopropylamide acting as bases. However, the reactions of the prepared 2-metylsulfinyl-2-methylsulfanyl ciclanones with aniline or methylamine were unsuccessful. The borohydride reduction of the 2-metylsulfinyl-2-methylsulfanyl ciclanones afforded the corresponding diastereoisomerically pure alcohols in ca. 70% yield, bearing, in the case of the tetralol derivative, the SR,C-1R,C-2R relative configuration. The two optically active sulfanylated 2-methylsulfinyl ciclanones could be prepared in good yields but as a scalemic mixture that precluded further studies in order to determine the stereochemical course of the carbonyl reduction. As for the addition reaction of the ethyl acetate lithium enolate to 2-methylsulfinyl-2-methylsulfanyl-1-indanone, the expected adduct was obtained in good yield but with poor diastereoselectivity. Under the same experimental conditions, the 2-methylsulfinyl-2-methylsulfanyl-1-tetralone underwent no reaction.

En dépit de sa rareté au sein des produits naturels et des processus biologiques, le fluor joue un rôle de plus en plus important dans nos vies quotidiennes. Un atome de fluor ou un groupement fluoré, lorsqu’il fait partie d’une molécule biologiquement active, permet d’améliorer drastiquement ses propriétés physiques, chimiques et biologiques. Le groupement -CHF2, en plus de posséder les propriétés remarquables communes à de nombreuses espèces émergentes fluorées, est considéré comme un bioisostère des groupements hydroxyle, thiol et amino. Il peut également être engagé dans des liaisons de type hydrogène grâce à son proton acide. Cependant, les voies de synthèse permettant d’introduire stéréosélectivement le groupe -CHF2 sont encore peu nombreuses. Par exemple, seuls peu de groupes ont concentré leurs efforts sur la synthèse d’alcools α,α-difluorométhylés. Afin de remédier à ce manque de méthodologies, deux stratégies ont été imaginées au sein de notre équipe. La première consiste à utiliser un sulfoxyde α,α-difluorométhylé énantiopur en tant qu’inducteur de chiralité. La seconde méthode repose sur l’utilisation de cyclopeptoïdes chiraux lors de la difluorométhylation énantiosélective de dérivés carbonylés dans des conditions de catalyse à transfert de phase. Ces deux stratégies ainsi que les résultats qui ont été obtenus au cours de ce projet de thèse sont exposés dans le présent manuscrit. / Despite being largely absent from natural products and biological processes, fluorine plays an increasingly important role in numerous areas of our daily life. The presence of fluorine atoms or fluoroalkyl groups in bioactive molecules can indeed deeply modify their physical, chemical and biological properties. In addition to these outstanding properties common to many emerging fluorinated groups, the -CHF2 group has been shown to be an interesting bioisostere of hydroxyl, thiol and amine groups and a strong hydrogen bond donor. However, in contrast to enantioselective trifluoromethylation, the enantioselective introduction of a difluoromethyl group is still in its infancy. For instance only few examples in the literature describe the synthesis of enantioenriched α,α-difluoromethyl alcohols. As part of our study to overcome this scarcity, we envisaged two different strategies to synthesise these compounds. The first method aimed to access highly enantioenriched α,α-difluoromethyl alcohols by using an enantiopure aryl α,α-difluoromethyl sulfoxide as chiral and traceless auxiliary. Phase transfer catalysis was chosen as a second strategy for the enantioselective difluoromethylation of carbonyl derivatives in presence of chiral cyclopeptoïds. Those two methods and the results obtained are discussed in this manuscript.

High temperature synthesis of nanocrystals in non-polar solvents typically produces materials with narrow size distribution and high yields. However, the mechanism leading to the preservation of monodispersity on depletion of monomers is not understood, for example, in the case of iron oxide nanoparticles. In our study, it was found that oleic acid, a surfactant added to the mixture of iron precursor and solvent, gradually decomposed to release carbon monoxide at 320°C. This strong reducing gaseous product had a substantial impact on the size distribution of nanocrystals produced. The reduced forms of iron oxide catalyzed the disproportionation of carbon monoxide resulting in a graphitic carbon deposit on the surface of nanoparticles. The graphite coating inhibited further growth of particles and prevented Ostwald ripening. Graphite presence was demonstrated by Raman spectroscopy and Fourier transform infrared spectroscopy. It was found that the amount of graphite deposited on the surface of nanocrystals increased with time at 320°C. Quantitative data regarding the carbon content was obtained by thermo gravimetric analysis and energy dispersive spectrometry. The surface activity of the nanocrystals was shown to be affected by the carbon coating in applications such as arsenic removal.

Para a síntese de um dos quatro possíveis estereoisômeros do ácido 3-(4- clorofenil)piroglutâmico, precursor da forma mais ativa do fármaco Baclofen, foram investigadas duas metodologias alternativas, cujas etapas principais eram, respectivamente, (i) a reação de Michael entre o N-acetamidomalonato de dietila ou de dibenzila com o 4-clorotiocinamato de metila ou fenila, na ausência de solvente e na presença de catalisadores de transferência de fase enantioméricamente puros, e (ii) a reação de Michael entre complexos de níquel (quirais ou aquirais), derivados da glicina, com a (5S)-N-(E-4-clorocinamoil)-5-metoxicarbonil-2-pirrolidinona. A primeira destas metodologias não conduziu a bons resultados, mas a investigação das causas da baixa estereosseletividade, observada para reações empregando tanto tiolésteres como chalcona, permitiu a proposição de um novo modelo de interação catalisador/doador/aceptor, em que o doador é o N-acetamidomalonato de dibenzila e o aceptor é a chalcona. Quanto às adições de Michael dos complexos de níquel, empregados como equivalentes nucleofílicos da glicina, as reações foram bem sucedidas. O par aceptor/doador que se mostrou mais adequado foi aquele composto pelo complexo de níquel, derivado da (L)-prolina, e pela (5S)-N-(E-4- clorocinamoil)-5-metoxicarbonil-2-pirrolidinona. Neste caso, o ácido (2R,3S)-3-(4- clorofenil)piroglutâmico foi obtido em rendimento global de 46%. Este resultado permite prever que, pelo emprego do mesmo aceptor, mas de estereoquímica absoluta contrária, é possível preparar o precursor do (R)- baclofen, que é o enantiômero mais ativo do fármaco em questão. / Two alternative methodologies were investigated aiming the synthesis of one of the four stereoisomers of the 3-(4-chlorophenyl)pyroglutamic acid, as a precursor of Baclofen, a drug used for the treatment of some neurological diseases. The key step for the first one was the asymmetric Michael addition of diethyl or dibenzil N- acetamidomalonate to methyl or phenyl 4-chlorotiocinnamate, in the absence of solvent, and employing enatiomerically pure phase transfer catalysts. A low degree of enantioselectivity was observed for all addition reactions of dibenzil N- acetamidomalonate to tiolesters or chalcone as Michael acceptors. The investigation of the origin of such lack of stereoselectivity allowed the proposal of a model for the diastereomeric transition states of the Michael addition of dibenzil N- acetamidomalonate to chalcone. As for the second synthetic methodology, the asymmetry generating step would be the Michael addition of glycine derived chiral or achiral nickel complexes to (5S)-N-(E-4-clorocinnamoil)-5-methoxycarbonyl-2- pirrolidinone. Best results were obtained for the Michael addition of a nickel complex, bearing (S)-2-[N-(N\'-benzylprolyl)amino]benzophenone as ligand , to (5S)-N-(E-4- clorocinnamoil)-5-methoxycarbonyl-2-pirrolidinone.Such reaction afforded the expected (S)-3-(4-chlorophenyl)pyroglutamic acid, in 46% yield. Such result can be extrapolated to the synthesis of the (R)-configured analog, precursor of the more active stereoisomer of Baclofen.

Le travail qui est décrit dans ce manuscrit de thèse traite de la chimie des superbases de type proazaphosphatranes, systèmes phosphorés bicycliques très utilisés en catalyse. L’objectif des investigations qui ont été menées à été d’ouvrir de nouvelles voies d’applications de ces catalyseurs. Afin de satisfaire cet objectif, plusieurs stratégies ont été envisagées. D’une part par la mise en confinement de la structure proazaphosphatrane et l’étude de l’influence de ce confinement sur la réactivité intrinsèque du proazaphosphatrane, et d’autre part par la catalyse en conditions bi-phasiques, que ce soit à l’interface entre une phase liquide et un solide ou entre deux phases liquides non-miscibles. Les recherches se sont orientées dans un premier temps sur la synthèse et la caractérisation complète d’un proazaphosphatrane supramoléculaire, obtenu par la fonctionnalisation par un proazaphosphatrane de la cavité supramoléculaire d’un récepteur macrobicyclique. Les séparations semi-préparatives des deux énantiomères d’un intermédiaire et de la molécule phosphorée finale ont également été réalisées, séparations qui ont permis de réaliser l’attribution des configurations absolues des deux structures macrobicycliques. La synthèse d’une famille de catalyseurs de type proazaphosphatrane supportés sur silice mésoporeuse a ensuite été réalisée, suivie de sa caractérisation texturale et structurale par les procédés physico-chimiques habituels, et enfin de sa mise en application dans des réactions d’intérêts de la synthèse organique. En dernier lieu, l’exploitation de la forme acide conjuguée des proazaphosphatranes, dite forme azaphosphatrane, dans des réactions de catalyse par transfert de phase a été entreprise. Il a ainsi put être démontré leur activité en tant qu’agent de transfert dans le cadre de quatre réactions significatives de la catalyse par transfert de phase en version racémique. Ce travail de thèse s’est finalement terminé par une ouverture vers la catalyse par transfert de phase en version asymétrique, par le biais de l’utilisation d’azaphosphatranes chiraux énantiopurs. / The work described in this PhD thesis deals with the chemistry of proazaphosphatrane-type superbases, which are highly reactive bicyclic phosphorous systems largely applied in catalysis. The main goal of these investigations was to devise new applications for their use in catalysis. In this way, several strategies were followed, with an emphasis on their molecular confinement and use in interfacial catalytic systems. In the first part, the manuscript describes the synthesis and characterisation of a supramolecular proazaphosphatrane obtained via the enclosing of a proazaphosphatrane moiety in a hemicryptophane-type macrobicyclic cavity. In parallel, the semi-preparative scale resolution of two macrobicyclic intermediates allowed us to assign their absolute configurations. In the second part, the synthesis and characterisation of a new class of superbases supported on mesoporous silica was achieved. The synthesis was followed by their application in base-catalysed organic reactions. The last part reports the use of their conjugate acids, or azaphosphatranes, in phase transfer catalysis. Their usefulness as achiral phase transfer agents in four relevant reactions was thus determined. The thesis ends with an introduction into asymmetric phase transfer catalysis, using enantiopure azaphosphatranes.

Le principal objectif de cette thèse a été d'exploiter des isoxazolidin-5-ones α-substituées aisément accessibles comme plateformes originales pour la synthèse d'acides β2,2-aminés énantiomériquement enrichis. Pour cela, nous avons montré que la catalyse par transfert de phase, avec l'utilisation de faibles quantités (2-3 mol%) d'un sel d'ammonium quaternaire énantiopur dédié, était l'outil adéquate pour la fonctionnalisation énantiosélective de la position α des isoxazolidin-5-ones et ainsi générer un centre quaternaire stéréogène. Cette stratégie organocatalytique a été appliquée à la création de liaison Carbone-Soufre, Carbone-Carbone et Carbone-Azote avec des excès énantiomériques de bons à excellents. Des réactions d'hydrogénolyse de la liaison N-O ou bien des réactions d'ouvertures via l'attaque de nucléophiles ont conduit à la formation des acides β2,2-aminés correspondants énantiomériquement enrichis. Enfin, de nouveaux sels d'ammonium quaternaires chiraux de type tropos, faciles d'accès, ont été conçus et évalués dans les réactions d'α-sulfanylation et d'addition conjuguée énantiosélectives dans les conditions de catalyse par transfert de phase mises en place. / The main purpose of this thesis was to use readily available α-substituted isoxazolidin-5-ones as original building blocks for the synthesis of enantioenriched β2,2-amino acids. Phase-transfer catalysis approach, with low loading of an appropriate quaternary ammonium salt, was found to be the most efficient tool for the enantioselective functionalization of the α-position of isoxazolidin-5-ones, allowed thereby to generate a stereogenic quaternary center. This organocatalytic strategy was applied to C-S, C-C and C-N bond formation with good to excellent enantiomeric excess. Hydrogenolysis reactions of the N-O bond or ring-opening reactions via nucleophilic addition reaction led to the corresponding enantioenriched β2,2-amino acids formation. Finally, new easily available chiral quaternary tropos-ammonium salts were designed and evaluated for both the enantioselective α-sulfanylation and conjuguated addition reactions.

Phase-transfer catalysts derived from the cinchona alkaloids cinchonine and cinchonidine are widely used in the asymmetric alkylation of substrates bearing moieties that resonance stabilize their enolates. The investigation of α-oxygenated esters revealed decreased α-proton acidity, indicating the oxygen's overall destabilizing effect on enolates by electron-pair repulsion. Alkylation of α-oxygenated aryl ketones with various alkyl halides proved successful with a cinchonidine catalyst, giving products with high yield and enantioselectivity. The resulting compounds were converted to esters through modified Baeyer-Villiger oxidation. Alkylation with indolyl electrophiles gave products that underwent decomposition under Baeyer-Villiger conditions. Alternative N-methylimidazolyl ketones were explored. Alkylated imidazolyl ketones, obtained in high yield and enantioselectivity, could be converted to esters through treatment with methyl triflate and basic methanol. This technique has the advantage of not requiring stoichiometric addition of chiral reagents, which is requisite when employing traditional chiral auxiliaries. This method's utility is demonstrated in the total asymmetric syntheses of (+)-kurasoin B and analogs, and 12-(S)-HETE. Kurasoin B is a fungal-derived natural compound possessing moderate farnesyl transfer (FTase) inhibitive activity (IC50 = 58.7 μM). FTase catalyzes post-translation modifications of membrane-bound Ras proteins, which function in signal cell transduction that stimulates cell growth and division. The oncogenic nature of mutated Ras proteins is demonstrated by their commonality in human tumors. Thus, FTase inhibitors like (+)-kurasoin B possess potential as cancer chemotherapy leads. Derivatization may enable structure-activity-relationship studies and greater FTase inhibition activity to be found. 12-(S)-HETE, a metabolite from a 12-lipoxygenase pathway from arachidonic acid, has been found to participate in a large number of physiological processes. Its transient presence in natural tissues makes total synthesis an attractive avenue for obtaining sufficient quantities for further study. Five asymmetric syntheses of 12-(S)-HETE have been reported. Three require chiral resolutions of racemates, with the undesired enantiomers being discarded or used for other applications. Asymmetric PTC alkylation is also described for aryl acetates, whose products were enantioenriched through recrystallization. This technique is applied to a total synthesis of the anti-inflammatory drug (S)-Naproxen.

No / Spheric and anisotropic gold nanoparticles (GNPs) such as rods, stars or nanoprism prepared using hexadecyltrimethyl ammonium bromide (CTAB) as the stabilising agent have received a great deal of interest in the last years. The literature procedures exploited lead to GNPs in aqueous solution. We herein describe a fast, efficient, and cheap method to transfer particles of different shapes from water into toluene solution via ligand exchange (CTAB to dodecanethiol), which was mediated by acetone as a cosolvent. Absorption spectra and TEM-pictures before and after the transfer revealed that the particles survived the transfer intact and without change in shape.