Silicone oils (polysiloxane) and elastomers are a class of hydrophobic polymers with an extensive range of uses. While the high hydrophobicity can be beneficial in a variety of applications, it is not universally the case. Modification strategies for both fluid and elastomeric polydimethylsiloxane (PDMS) must be employed to create silicones with the appropriate properties for a given application, including enhanced hydrophilicity. Derivatization of PDMS leads to functional silicones with unique properties and added value. Strategies have been developed to modify both fluid and elastomeric PDMS, however, they all have varying degrees of drawbacks: the use of sophisticated equipment or expensive catalysts, restrictions to certain types of solvents, cumbersome multi-step synthetic procedures and surface reversion are some of the challenges faced. There is an opportunity to develop a simple and generic method for the controlled functionalization of PDMS. The Sharpless concept of ‘Click’ chemistry was an ideal approach to solving some of these challenges. Following nature’s lead, these reactions that are modular, wide in scope, high yielding, have simple reaction conditions and generate inoffensive byproducts. Herein, a synthetic method to functionalize silicones using the thermal Huisgen 1,3-dipolar cycloaddition of azides to alkynes is described. Initial exploration focused on the creation of inherently reactive elastomers that could be modified with a model hydrophilic moiety, poly(ethylene glycol). This was extended to the creation of amphiphilic multi-functional polysiloxanes and amphiphilic networks. Furthermore, the ‘Click’ approach was used to solve challenges faced in applications where silicones find use. The method described overcomes silicone modification challenges. The cycloaddition reaction is tolerant to many reaction conditions, is orthoganol to a variety of chemical reactions, does not require the use of a catalyst, the starting functional groups and bonds formed are stable and the reaction is high yielding, positioning the Huisgen ‘click’ reaction is an exceptional synthetic tool for the silicone chemist. / Dissertation / Doctor of Philosophy (PhD) / Polydimethylsiloxane (PDMS or silicone) fluids and elastomers are materials that find use in many applications owing to the many desirable properties they possess; personal care products, electrical insulators, sealants and biomedical are examples of products containing silicone. Native PDMS is highly hydrophobic (water repellent) and certain applications require silicones that are more compatible in environments containing water. Methods have been developed to modify both fluid and elastomeric silicones; incorporation of different molecules or polymers can enhance the properties of silicone for various applications or create unique materials. However, many of these methods have certain drawbacks: the use of sophisticated equipment, expensive ingredients, or a lack of permanence. For this reason, a new method to modify fluid and elastomeric silicones has been developed. The new method is based on the concept of ‘Click’ chemistry and has overcome some of challenges associated with other modification methods.

No description available.

L'une des préoccupations de la chimie moderne est de développer des procédés éco-compatibles : une tendance consiste à remplacer les solvants organiques par les Liquides Ioniques (LI). Ainsi ces travaux décrivent l'utilisation des LI dans deux réactions à économie d'atomes : l'addition de Michael et la réaction de cycloaddition 1,3-dipolaire catalysée (ou non) par un sel de cuivre (CuAAC). La première partie des travaux relate l'emploi de Liquides Ioniques Super-Acides (LISA), connus pour générer une activation électrophile. Une optimisation du LISA a été effectuée sur une réaction-modèle, puis l'application à d'autres électrophiles et nucléophiles a été étudiée. La pureté du LISA influe sur la chimiosélectivité : s’il est partiellement hydrolysé, la réaction d'annélation de Robinson devient prépondérante. La version asymétrique du processus a été abordée, montrant qu'il est possible d'obtenir un excès énantiomérique à partir de dérivés d'acides aminés. La seconde partie de l'étude a permis de mettre au point une synthèse de (triazolylméthyl)vinylphosphonates à partir d'un acétoxyméthylvinylphosphonate selon une procédure monotope reposant sur la cycloaddition 1,3-dipolaire dans différents LI. Nous avons ensuite montré que le LI joue aussi le rôle d'activateur pour cette réaction. / In the context of sustainable chemistry, an alternative to conventional organic solvents is the use of ionic liquids. These works reported here aims to describe the use of ionic liquids (IL) in two atoms economy reactions, namely the Michael addition reaction and 1,3-dipolar cycloaddition catalyzed (or not) by a copper salt (CuAAC). In the first part of the work reports the use of Super-Acid Ionic Liquids (SAIL), which initiate an electrophilic activation. After optimization of SAIL on a reaction model, application to other electrophiles and nucleophiles is discussed. The purity of SAIL affects the chemioselectivity: if the SAIL is partially hydrolyzed, a Robinson annulation predominates. The asymmetric version of the process is investigated, showing that it is possible to carry out an enantioselective reaction with amino acid derived SAIL. The second part of the study deals with setting up an original synthesis of (triazolylmethyl)vinylphosphonate from acetoxymethylvinylphosphonate using a one-pot procedure involving a 1,3-dipolar cycloaddition in different LI. We further showed that the ionic liquid can also act as an activator for this reaction.

In the first part of this study, four new chiral ligands (FAM) were synthesized and used in catalytic amounts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method leads to the synthesis of chiral pyrrolidines, which are found in the structure of many biologically active natural compounds and drugs. It was found that using 10 mol% of one of these chiral ligands with different dipolarophiles (dimethyl maleate, dimethyl fumarate, methyl acrylate, tert-butyl acrylate, and Nmethylmaleimide), pyrrolidine derivatives could be synthesized in up to 94% yield and 95% ee. In the second part of the study, the catalytic activity of these chiral ligands were tested with titanium in asymmetric alkynylzinc addition reactions to aldehydes. By this method, chiral propargylic alcohols, which are important precursors for the natural products and pharmaceuticals can be synthesized. Using our catalyst, chiral propargylic alcohols were obtained in up to 96% yield and 98% ee. Although, most of the catalyst systems in the literature worked only with aromatic or aliphatic aldehydes and phenylacetylene, the catalyst system developed in this study worked with four different types of aldehydes (aromatic, aliphatic, heteroaromatic and a,b-unsaturated) and two different aliphatic acetylenes very successfully. Additionally, chiral ligand can be recovered in more than 90% yield and reused without losing its activity.

In this study new twelve phosphorus based chiral ligands were synthesized and characterized. Then the catalytic activity of these chiral ligands was tested with Cu(II) and Ag(I) salts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method provides the synthesis of different pyrrolidine derivatives with up to four stereogenic centers. Pyrrolidine derivatives are found in the structure of many biologically active natural compounds and drugs. Therefore the asymmetric synthesis of these compounds is highly important and many groups are involved in this area. As the precursor of the azomethine ylides, N-benzyliden-glycinmethylester, N-(4-methoxy benzyliden)-glycinmethylester, N-(naphthalene-1-ylmethylene)-amino-acetic acid methyl ester, and N-(naphthalen-2-ylmethylene)-amino-acetic acid methyl ester were synthesized and used. As the dipolarophiles, methyl acrylate, dimethyl maleate and N-methyl maleimide were used. Using these imines and dipolarophiles with 6 mol % of one of the P-FAM chiral ligands in the presence of Ag(I) salt, pyrrolidine derivatives were synthesized in up to 95% yield and 89% enantioselectivity. Additionally, chiral ligand was recovered in more than 80% yield and reused without losing its activity.

As reações de cicloadição 1,3-dipolar são uma poderosa ferramenta para a síntese de uma variedade de anéis heterocíclicos de cinco membros. A cicloadição de óxidos de nitrila à olefinas, em particular, é de considerável interesse para a obtenção de isoxazolinas, que são intermediários versáteis na síntese de produtos naturais e de materiais com potencial aplicação como cristais líquidos. A Teoria do Funcional da Densidade foi utilizada para estudar o mecanismo da reação cicloadição [3+2] 1,3-dipolar que ocorre, inicialmente, entre o óxido de benzonitrila e o ácido vinilacético. Para tal, foram empregados os funcionais PBE1PBE, B3LYP e CAM-B3LYP, no nível 6-311+G(2d,p). O efeito do solvente foi avaliado através dos modelos PCM e CPCM, com os solventes THF, acetonitrila e formamida. A análise dos Orbitais Moleculares de Fronteira e do recente modelo da distorção e interação do estado de transição (TS), foram utilizadas para explicar a regioquímica dos produtos obtidos e a formação do bisaduto 2:1, originário de duas sucessivas cicloadições envolvendo o óxido de benzonitrila. Na primeira etapa da reação, os cálculos evidenciaram a formação do produto 3,5-dissubstiuído. Embora existam diferenças quantitativas nas barreiras de ativação e reação calculadas com os três diferentes funcionais, a previsão dos produtos majoritários e estados de transição mais favoráveis é a mesma, independentemente do funcional utilizado. Contudo, a conformação dos estados de transição e dos produtos intermediário e final da reação sofre uma pequena alteração com a inclusão do efeito do solvente. A energia de ativação nas duas cicloadições aumenta com o incremento da polaridade do solvente, porém, a possibilidade de formação de uma ligação de hidrogênio no estado de transição é responsável por uma diminuição na energia total de ativação. Esse resultado está diretamente vinculado à polaridade do TS. Quando comparados os resultados obtidos com os dois modelos de solvente, observou-se que ΔE≠ e ΔEreação são essencialmente as mesmas, embora as energias eletrônicas calculadas com CPCM sejam levemente inferiores às calculadas com PCM. / The 1,3-dipolar cycloaddition reactions are a powerful tool for synthesizing a wide range of 5-membered heterocyclic rings. Particularly, the cycloaddition of nitrile oxides to olefins is considerably interesting to obtain isoxazolines, which are versatile intermediaries in the synthesis of natural products and materials with potential application such as liquid crystals. The Density Functional Theory has been used to study the [3+2] 1,3-dipolar cycloaddition reaction mechanism that initially occurs between benzonitrile oxide and vinylacetic acid. To do that, PBE1PBE, B3LYP and CAM-B3LYP functionals have been used at level 6- 311+G(2d,p). The solvent effect was evaluated through the PCM and CPCM models, with the THF, acetonitrile and formamide solvents. The analysis of the Frontier Molecular Orbitals and of the recent distortion and interaction model of transition state (TS) have been used to explain the regiochemistry of the products obtained and the formation of the bisadduct 2:1, which is originated from two successive cycloadditions involving benzonitrile oxide. In the first reaction step, the calculations showed the formation of the 3,5-dissubstituted product. Although there are quantitative differences in the activation and reaction barriers calculated with the three different functionals, the forecasting of more favorable majoritary products and transition states is the same, no matter the functional used. However, the conformation of the transition states and of the final and intermediary products of the reaction is slightly changed by the inclusion of the solvent effect. The activation energy of both cycloadditions increases with the polarity increment of the solvent, but the possibility of formation of a hydrogen bond in the transition state is responsible for a reduction of the total activation energy. That result is directly linked to the TS polarity. When we compare the results obtained with the two solvent models, we observe that ΔE≠ and ΔEreaction are essentially the same, although the electronic energies calculated with CPCM are slightly smaller than the ones calculated with PCM.

As reações de cicloadição 1,3-dipolar são uma poderosa ferramenta para a síntese de uma variedade de anéis heterocíclicos de cinco membros. A cicloadição de óxidos de nitrila à olefinas, em particular, é de considerável interesse para a obtenção de isoxazolinas, que são intermediários versáteis na síntese de produtos naturais e de materiais com potencial aplicação como cristais líquidos. A Teoria do Funcional da Densidade foi utilizada para estudar o mecanismo da reação cicloadição [3+2] 1,3-dipolar que ocorre, inicialmente, entre o óxido de benzonitrila e o ácido vinilacético. Para tal, foram empregados os funcionais PBE1PBE, B3LYP e CAM-B3LYP, no nível 6-311+G(2d,p). O efeito do solvente foi avaliado através dos modelos PCM e CPCM, com os solventes THF, acetonitrila e formamida. A análise dos Orbitais Moleculares de Fronteira e do recente modelo da distorção e interação do estado de transição (TS), foram utilizadas para explicar a regioquímica dos produtos obtidos e a formação do bisaduto 2:1, originário de duas sucessivas cicloadições envolvendo o óxido de benzonitrila. Na primeira etapa da reação, os cálculos evidenciaram a formação do produto 3,5-dissubstiuído. Embora existam diferenças quantitativas nas barreiras de ativação e reação calculadas com os três diferentes funcionais, a previsão dos produtos majoritários e estados de transição mais favoráveis é a mesma, independentemente do funcional utilizado. Contudo, a conformação dos estados de transição e dos produtos intermediário e final da reação sofre uma pequena alteração com a inclusão do efeito do solvente. A energia de ativação nas duas cicloadições aumenta com o incremento da polaridade do solvente, porém, a possibilidade de formação de uma ligação de hidrogênio no estado de transição é responsável por uma diminuição na energia total de ativação. Esse resultado está diretamente vinculado à polaridade do TS. Quando comparados os resultados obtidos com os dois modelos de solvente, observou-se que ΔE≠ e ΔEreação são essencialmente as mesmas, embora as energias eletrônicas calculadas com CPCM sejam levemente inferiores às calculadas com PCM. / The 1,3-dipolar cycloaddition reactions are a powerful tool for synthesizing a wide range of 5-membered heterocyclic rings. Particularly, the cycloaddition of nitrile oxides to olefins is considerably interesting to obtain isoxazolines, which are versatile intermediaries in the synthesis of natural products and materials with potential application such as liquid crystals. The Density Functional Theory has been used to study the [3+2] 1,3-dipolar cycloaddition reaction mechanism that initially occurs between benzonitrile oxide and vinylacetic acid. To do that, PBE1PBE, B3LYP and CAM-B3LYP functionals have been used at level 6- 311+G(2d,p). The solvent effect was evaluated through the PCM and CPCM models, with the THF, acetonitrile and formamide solvents. The analysis of the Frontier Molecular Orbitals and of the recent distortion and interaction model of transition state (TS) have been used to explain the regiochemistry of the products obtained and the formation of the bisadduct 2:1, which is originated from two successive cycloadditions involving benzonitrile oxide. In the first reaction step, the calculations showed the formation of the 3,5-dissubstituted product. Although there are quantitative differences in the activation and reaction barriers calculated with the three different functionals, the forecasting of more favorable majoritary products and transition states is the same, no matter the functional used. However, the conformation of the transition states and of the final and intermediary products of the reaction is slightly changed by the inclusion of the solvent effect. The activation energy of both cycloadditions increases with the polarity increment of the solvent, but the possibility of formation of a hydrogen bond in the transition state is responsible for a reduction of the total activation energy. That result is directly linked to the TS polarity. When we compare the results obtained with the two solvent models, we observe that ΔE≠ and ΔEreaction are essentially the same, although the electronic energies calculated with CPCM are slightly smaller than the ones calculated with PCM.

As reações de cicloadição 1,3-dipolar são uma poderosa ferramenta para a síntese de uma variedade de anéis heterocíclicos de cinco membros. A cicloadição de óxidos de nitrila à olefinas, em particular, é de considerável interesse para a obtenção de isoxazolinas, que são intermediários versáteis na síntese de produtos naturais e de materiais com potencial aplicação como cristais líquidos. A Teoria do Funcional da Densidade foi utilizada para estudar o mecanismo da reação cicloadição [3+2] 1,3-dipolar que ocorre, inicialmente, entre o óxido de benzonitrila e o ácido vinilacético. Para tal, foram empregados os funcionais PBE1PBE, B3LYP e CAM-B3LYP, no nível 6-311+G(2d,p). O efeito do solvente foi avaliado através dos modelos PCM e CPCM, com os solventes THF, acetonitrila e formamida. A análise dos Orbitais Moleculares de Fronteira e do recente modelo da distorção e interação do estado de transição (TS), foram utilizadas para explicar a regioquímica dos produtos obtidos e a formação do bisaduto 2:1, originário de duas sucessivas cicloadições envolvendo o óxido de benzonitrila. Na primeira etapa da reação, os cálculos evidenciaram a formação do produto 3,5-dissubstiuído. Embora existam diferenças quantitativas nas barreiras de ativação e reação calculadas com os três diferentes funcionais, a previsão dos produtos majoritários e estados de transição mais favoráveis é a mesma, independentemente do funcional utilizado. Contudo, a conformação dos estados de transição e dos produtos intermediário e final da reação sofre uma pequena alteração com a inclusão do efeito do solvente. A energia de ativação nas duas cicloadições aumenta com o incremento da polaridade do solvente, porém, a possibilidade de formação de uma ligação de hidrogênio no estado de transição é responsável por uma diminuição na energia total de ativação. Esse resultado está diretamente vinculado à polaridade do TS. Quando comparados os resultados obtidos com os dois modelos de solvente, observou-se que ΔE≠ e ΔEreação são essencialmente as mesmas, embora as energias eletrônicas calculadas com CPCM sejam levemente inferiores às calculadas com PCM. / The 1,3-dipolar cycloaddition reactions are a powerful tool for synthesizing a wide range of 5-membered heterocyclic rings. Particularly, the cycloaddition of nitrile oxides to olefins is considerably interesting to obtain isoxazolines, which are versatile intermediaries in the synthesis of natural products and materials with potential application such as liquid crystals. The Density Functional Theory has been used to study the [3+2] 1,3-dipolar cycloaddition reaction mechanism that initially occurs between benzonitrile oxide and vinylacetic acid. To do that, PBE1PBE, B3LYP and CAM-B3LYP functionals have been used at level 6- 311+G(2d,p). The solvent effect was evaluated through the PCM and CPCM models, with the THF, acetonitrile and formamide solvents. The analysis of the Frontier Molecular Orbitals and of the recent distortion and interaction model of transition state (TS) have been used to explain the regiochemistry of the products obtained and the formation of the bisadduct 2:1, which is originated from two successive cycloadditions involving benzonitrile oxide. In the first reaction step, the calculations showed the formation of the 3,5-dissubstituted product. Although there are quantitative differences in the activation and reaction barriers calculated with the three different functionals, the forecasting of more favorable majoritary products and transition states is the same, no matter the functional used. However, the conformation of the transition states and of the final and intermediary products of the reaction is slightly changed by the inclusion of the solvent effect. The activation energy of both cycloadditions increases with the polarity increment of the solvent, but the possibility of formation of a hydrogen bond in the transition state is responsible for a reduction of the total activation energy. That result is directly linked to the TS polarity. When we compare the results obtained with the two solvent models, we observe that ΔE≠ and ΔEreaction are essentially the same, although the electronic energies calculated with CPCM are slightly smaller than the ones calculated with PCM.

In this thesis, different cycloaddition reactions, such as the enantioselective 1,3-dipolar-cycloaddition, which takes place between in situ generated stabilized azomethine ylides, and electrophilic alkenes, and the diastereoselective multicomponent reactions Amine-Aldehyde-Dienophile (AAD) or Phosphoramidate-Aldehyde-Dienophile (PAD) are described. In Chapter 1, an asymmetric 1,3-dipolar cycloaddition reaction involving an imino ester with tert-butyl acrylate was carried out using a silver(I) complex with double chirality, formed from a chiral phosphoramidite and chiral silver binolphosphate(I). The goal of this reaction is to synthesize key enantiomerically enriched structures to access the GSK-third generation of HCV inhibitors. In Chapter 2, the synthesis of polysubstituted cyclohex-2-enylamines using the multicomponent Amine-Aldehyde-Dienophile reaction involving benzyl or 4-methoxybenzylamine, is described. The study the diastereoselective version, employing commercially available chiral benzylic amines, or even a maleimide with the chiral information at the nitrogen atom, are also reported. In Chapter 3, the synthesis of polysubstituted cyclohex-2-enylamines derivatives using the multicomponent Phosphoramidate-Aldehyde-Dienophile (PAD), is described. Several series of N-substituted phosphoramidates reacted with α,β-unsaturated aldehydes, bearing hydrogen atoms at the γ-position, in good yields.

No description available.