Neste trabalho foram realizados estudos de uma rota sintética comum para a obtenção de duas lactonas sesquiterpênicas, conocenolido A e conocenolido B. Estes compostos, por apresentarem um novo esqueleto carbônico, fazem parte de uma classe de produtos naturais sesquiterpênicos denominados tremulanos, dos quais se destacam por apresentarem a ruptura de uma ligação C-C do esqueleto básico, de onde vem a denominação 5,6-seco-tremulanos. Para fins de estudos sintéticos podemos destacar, na molécula desses tremulanos, as seguintes unidades estruturais: a) um ciclopentano substituído, b) uma ligação dupla tetrassubstituída e c) um anel de lactona (uma -lactona presente em conocenolido A e uma -lactona em conocenolido B). Em nossa proposta inicial, a estrutura do anel de ciclopentano seria preparada por contração de anel de uma epoxiciclo-hexanona. Ao contrário, porém, do esperado com base nos exemplos da literatura, esta reação não produziu nada de 2-formilciclopentanona. A estrutura do anel de ciclopentano desejada foi, então, preparada por um caminho alternativo partindo da cetona metílica e vinílica. Nos estudos relacionados à preparação da ligação dupla tetrassubstituída foram empregadas as reações clássicas de olefinação (Wittig e HWE) e reações de condensação (Stobbe e Reformatsky). O trabalho com fosforanas (Reagente de Wittig) envolveu um estudo de dinâmica rotacional destes compostos por RMN. Os estudos da reação tipo Reformatsky foram realizados tanto no contexto de preparação de olefinas quanto na obtenção de lactonas (derivados do ácido paracônico). Um estudo detalhado das estruturas destas lactonas foi realizado por meio da determinação estrutural dos derivados do ácido paracônico. / In this work were realized studies towards a common synthetic route for the preparation of two sesquiterpenes lactones, conocenolide A and conocenolide B. These compounds belong to a class of sesquiterpenoids known as tremulanes presenting a novel carbon skeleton. A special structural feature of both lactones that set them apart from class is the lack of a carbon-carbon bond in the basic skeleton, so their denomination 5,6-seco-tremulanes. For the purpose of synthetic studies, we highlight in the molecule of these tremulanes the following structural units: a) one substituted cyclopentane, b) one tetrasubstitued double bond and c) one lactone ring ( one -lactone ring is present in conocenolide A and one -lactone ring is present in conocenolide B). In our initial proposal, the structure of the cyclopentane ring would be prepared by ring contraction of an epoxycyclohexanone. However, in spite of some literature examples, the ring contraction to provide the 2-formyl-cyclopentanone did not occur. The desired cyclopentane ring was prepared by an alternative route from methyl vinyl ketone. The studies related to the preparation of tetrasubstituted double bond was based on classical olefination reactions (Wittig and Horner-Emmons) and condensation reactions (Stobbe and Reformatsky). In addition, a NMR study dealing with the rotational dynamics of phosphoranes was realized. Studies exploring the versatility of a Reformatsky-type reaction were carried out both in the context of olefin preparation as well as for the preparation of lactones (paraconic acid derivatives). A detailed study of the structures of these lactones was accomplished through structural determination of paraconic acid derivatives.

Optimized methods for the regioselective and stereospecific synthesis of both trisubstituted and tetrasubstituted olefins as single isomers from E-β-chloro-α-iodo-α,β-unsaturated esters have been developed from previous work done in the Ogilvie lab. These optimized methods have led to the synthesis of trans isomeric enediynes that can be photoisomerized to their respective cis isomers and subsequently undergo microwave-assisted Bergman cycloaromatizations. Furthermore, both cis and trans isomeric enediynes that have propargyl ether substituents have been found to be able to undergo photoactivated Bergman cyclizations without the need for an intermolecular hydrogen donor. A mechanism study has confirmed that the Bergman cyclization products that form without the presence of an intermolecular hydrogen donor undergo a series of 1,5-hydrogen shifts as intermediates. A series of optimizations to these reactions were carried out, in part by utilizing electron-donating or electron-withdrawing functional groups to help stabilize the resulting radicals that form on the intermediates, and thus increase the yield of the associated Bergman cyclization products.

Optimized methods for the regioselective and stereospecific synthesis of both trisubstituted and tetrasubstituted olefins as single isomers from E-β-chloro-α-iodo-α,β-unsaturated esters have been developed from previous work done in the Ogilvie lab. These optimized methods have led to the synthesis of trans isomeric enediynes that can be photoisomerized to their respective cis isomers and subsequently undergo microwave-assisted Bergman cycloaromatizations. Furthermore, both cis and trans isomeric enediynes that have propargyl ether substituents have been found to be able to undergo photoactivated Bergman cyclizations without the need for an intermolecular hydrogen donor. A mechanism study has confirmed that the Bergman cyclization products that form without the presence of an intermolecular hydrogen donor undergo a series of 1,5-hydrogen shifts as intermediates. A series of optimizations to these reactions were carried out, in part by utilizing electron-donating or electron-withdrawing functional groups to help stabilize the resulting radicals that form on the intermediates, and thus increase the yield of the associated Bergman cyclization products.

Optimized methods for the regioselective and stereospecific synthesis of both trisubstituted and tetrasubstituted olefins as single isomers from E-β-chloro-α-iodo-α,β-unsaturated esters have been developed from previous work done in the Ogilvie lab. These optimized methods have led to the synthesis of trans isomeric enediynes that can be photoisomerized to their respective cis isomers and subsequently undergo microwave-assisted Bergman cycloaromatizations. Furthermore, both cis and trans isomeric enediynes that have propargyl ether substituents have been found to be able to undergo photoactivated Bergman cyclizations without the need for an intermolecular hydrogen donor. A mechanism study has confirmed that the Bergman cyclization products that form without the presence of an intermolecular hydrogen donor undergo a series of 1,5-hydrogen shifts as intermediates. A series of optimizations to these reactions were carried out, in part by utilizing electron-donating or electron-withdrawing functional groups to help stabilize the resulting radicals that form on the intermediates, and thus increase the yield of the associated Bergman cyclization products.

Neste trabalho foram realizados estudos de uma rota sintética comum para a obtenção de duas lactonas sesquiterpênicas, conocenolido A e conocenolido B. Estes compostos, por apresentarem um novo esqueleto carbônico, fazem parte de uma classe de produtos naturais sesquiterpênicos denominados tremulanos, dos quais se destacam por apresentarem a ruptura de uma ligação C-C do esqueleto básico, de onde vem a denominação 5,6-seco-tremulanos. Para fins de estudos sintéticos podemos destacar, na molécula desses tremulanos, as seguintes unidades estruturais: a) um ciclopentano substituído, b) uma ligação dupla tetrassubstituída e c) um anel de lactona (uma -lactona presente em conocenolido A e uma -lactona em conocenolido B). Em nossa proposta inicial, a estrutura do anel de ciclopentano seria preparada por contração de anel de uma epoxiciclo-hexanona. Ao contrário, porém, do esperado com base nos exemplos da literatura, esta reação não produziu nada de 2-formilciclopentanona. A estrutura do anel de ciclopentano desejada foi, então, preparada por um caminho alternativo partindo da cetona metílica e vinílica. Nos estudos relacionados à preparação da ligação dupla tetrassubstituída foram empregadas as reações clássicas de olefinação (Wittig e HWE) e reações de condensação (Stobbe e Reformatsky). O trabalho com fosforanas (Reagente de Wittig) envolveu um estudo de dinâmica rotacional destes compostos por RMN. Os estudos da reação tipo Reformatsky foram realizados tanto no contexto de preparação de olefinas quanto na obtenção de lactonas (derivados do ácido paracônico). Um estudo detalhado das estruturas destas lactonas foi realizado por meio da determinação estrutural dos derivados do ácido paracônico. / In this work were realized studies towards a common synthetic route for the preparation of two sesquiterpenes lactones, conocenolide A and conocenolide B. These compounds belong to a class of sesquiterpenoids known as tremulanes presenting a novel carbon skeleton. A special structural feature of both lactones that set them apart from class is the lack of a carbon-carbon bond in the basic skeleton, so their denomination 5,6-seco-tremulanes. For the purpose of synthetic studies, we highlight in the molecule of these tremulanes the following structural units: a) one substituted cyclopentane, b) one tetrasubstitued double bond and c) one lactone ring ( one -lactone ring is present in conocenolide A and one -lactone ring is present in conocenolide B). In our initial proposal, the structure of the cyclopentane ring would be prepared by ring contraction of an epoxycyclohexanone. However, in spite of some literature examples, the ring contraction to provide the 2-formyl-cyclopentanone did not occur. The desired cyclopentane ring was prepared by an alternative route from methyl vinyl ketone. The studies related to the preparation of tetrasubstituted double bond was based on classical olefination reactions (Wittig and Horner-Emmons) and condensation reactions (Stobbe and Reformatsky). In addition, a NMR study dealing with the rotational dynamics of phosphoranes was realized. Studies exploring the versatility of a Reformatsky-type reaction were carried out both in the context of olefin preparation as well as for the preparation of lactones (paraconic acid derivatives). A detailed study of the structures of these lactones was accomplished through structural determination of paraconic acid derivatives.

Optimized methods for the regioselective and stereospecific synthesis of both trisubstituted and tetrasubstituted olefins as single isomers from E-β-chloro-α-iodo-α,β-unsaturated esters have been developed from previous work done in the Ogilvie lab. These optimized methods have led to the synthesis of trans isomeric enediynes that can be photoisomerized to their respective cis isomers and subsequently undergo microwave-assisted Bergman cycloaromatizations. Furthermore, both cis and trans isomeric enediynes that have propargyl ether substituents have been found to be able to undergo photoactivated Bergman cyclizations without the need for an intermolecular hydrogen donor. A mechanism study has confirmed that the Bergman cyclization products that form without the presence of an intermolecular hydrogen donor undergo a series of 1,5-hydrogen shifts as intermediates. A series of optimizations to these reactions were carried out, in part by utilizing electron-donating or electron-withdrawing functional groups to help stabilize the resulting radicals that form on the intermediates, and thus increase the yield of the associated Bergman cyclization products.

Ce projet de recherche consiste en l’étude de la réactivité et de la sélectivité de nouveaux catalyseurs de métathèse d’oléfines à base de ruthénium lors de réaction de fermeture de cycle par métathèse d’oléfines (RCM). L’emphase de cette étude repose sur l’évaluation de nouveaux catalyseurs possédant un ligand NHC (carbène N-hétérocyclique) C1-symétrique développés par le laboratoire Collins pour des réactions de désymétrisations asymétriques de méso-triènes par ARCM. Le projet a été séparé en deux sections distinctes. La première section concerne la formation d’oléfines trisubstituées par ARCM de méso-triènes. La seconde section consiste en la formation d’oléfines tétrasubstituées par le biais de la RCM de diènes et de la ARCM de méso-triènes. Il est à noter qu’il n’y a aucun précédent dans la littérature concernant la formation d’oléfines tétrasubstituées suite à une désymétrisation par ARCM. Lors de l’étude concernant la formation d’oléfines trisubstituées, une étude de cinétique a été entreprise dans le but de mieux comprendre la réactivité des différents catalyseurs. Il a été possible d’observer que le groupement N-alkyle a une grande influence sur la réactivité du catalyseur. Une étude de sélectivité a ensuite été entreprise pour déterminer si le groupement N-alkyle génère aussi un effet sur la sélectivité des catalyseurs. Cette étude a été effectuée par l’entremise de réactions de désymétrisation d’une variété de méso-triènes. En ce qui a trait à la formation d’oléfines tétrasubstituées, une étude de la réactivité des différents catalyseurs a été effectuée par l’intermédiaire de malonates de diéthyldiméthallyle. Il a encore une fois a été possible d’observer que le groupement N-alkyle possède un effet important sur la réactivité du catalyseur. Une étude de sélectivité a ensuite été entreprise pour déterminer si le groupement iv N-alkyle génère aussi un effet sur la sélectivité des catalyseurs. Cette étude a été effectuée par l’entremise de réactions de désymétrisation de différents mésotriènes. / This research consists in the study of the reactivity and selectivity of new chiral Ru-based olefin metathesis catalysts in ring-closing metathesis (RCM) reactions. The study focused on evaluating new catalysts possessing C1- symmetric NHC (N-heterocyclic carbene) ligands developed in our laboratories for asymmetric desymmetrization reactions of meso-trienes. The research was divided into two distinct sections, the first concerns the asymmetric ring closing metathesis (ARCM) processes that form trisubstituted olefins from meso-trienes. The second concerns the RCM and ARCM processes that form tetrasubstituted olefins from meso-trienes. It can be observed that there is no precedent in the literature concerning the formation of tetrasubstituted olefins via ARCM. During the investigation concerning the formation of trisubstituted olefins, a kinetic study was done to have better understanding of the catalyst selectivity. With this study in hand, it was possible to observe the effect induced by the N-alkyl group on the catalysts’ reactivity. A selectivity study was done to observe if the Nalkyl group could affects the catalysts’ selectivity. These investigations were done using a variety of meso-trienes in desymmetrization reactions to afford trisubstituted olefins. Concerning the formation of tetrasubstituted olefins, the catalysts’ reactivity was investigated in RCM processes involving diethyldimethallyl malonates. Once again, an effect induced by the N-alkyl group was observed concerning the reactivity of the catalysts. A selectivity study was performed. As for ARCM processes forming trisubstituted olefins, the N-alkyl group also had an impact on the selectivity of the catalysts. This investigation was done with ARCM desymmetrization of meso-trienes.

Ce projet de recherche consiste en l’étude de la réactivité et de la sélectivité de nouveaux catalyseurs de métathèse d’oléfines à base de ruthénium lors de réaction de fermeture de cycle par métathèse d’oléfines (RCM). L’emphase de cette étude repose sur l’évaluation de nouveaux catalyseurs possédant un ligand NHC (carbène N-hétérocyclique) C1-symétrique développés par le laboratoire Collins pour des réactions de désymétrisations asymétriques de méso-triènes par ARCM. Le projet a été séparé en deux sections distinctes. La première section concerne la formation d’oléfines trisubstituées par ARCM de méso-triènes. La seconde section consiste en la formation d’oléfines tétrasubstituées par le biais de la RCM de diènes et de la ARCM de méso-triènes. Il est à noter qu’il n’y a aucun précédent dans la littérature concernant la formation d’oléfines tétrasubstituées suite à une désymétrisation par ARCM. Lors de l’étude concernant la formation d’oléfines trisubstituées, une étude de cinétique a été entreprise dans le but de mieux comprendre la réactivité des différents catalyseurs. Il a été possible d’observer que le groupement N-alkyle a une grande influence sur la réactivité du catalyseur. Une étude de sélectivité a ensuite été entreprise pour déterminer si le groupement N-alkyle génère aussi un effet sur la sélectivité des catalyseurs. Cette étude a été effectuée par l’entremise de réactions de désymétrisation d’une variété de méso-triènes. En ce qui a trait à la formation d’oléfines tétrasubstituées, une étude de la réactivité des différents catalyseurs a été effectuée par l’intermédiaire de malonates de diéthyldiméthallyle. Il a encore une fois a été possible d’observer que le groupement N-alkyle possède un effet important sur la réactivité du catalyseur. Une étude de sélectivité a ensuite été entreprise pour déterminer si le groupement iv N-alkyle génère aussi un effet sur la sélectivité des catalyseurs. Cette étude a été effectuée par l’entremise de réactions de désymétrisation de différents mésotriènes. / This research consists in the study of the reactivity and selectivity of new chiral Ru-based olefin metathesis catalysts in ring-closing metathesis (RCM) reactions. The study focused on evaluating new catalysts possessing C1- symmetric NHC (N-heterocyclic carbene) ligands developed in our laboratories for asymmetric desymmetrization reactions of meso-trienes. The research was divided into two distinct sections, the first concerns the asymmetric ring closing metathesis (ARCM) processes that form trisubstituted olefins from meso-trienes. The second concerns the RCM and ARCM processes that form tetrasubstituted olefins from meso-trienes. It can be observed that there is no precedent in the literature concerning the formation of tetrasubstituted olefins via ARCM. During the investigation concerning the formation of trisubstituted olefins, a kinetic study was done to have better understanding of the catalyst selectivity. With this study in hand, it was possible to observe the effect induced by the N-alkyl group on the catalysts’ reactivity. A selectivity study was done to observe if the Nalkyl group could affects the catalysts’ selectivity. These investigations were done using a variety of meso-trienes in desymmetrization reactions to afford trisubstituted olefins. Concerning the formation of tetrasubstituted olefins, the catalysts’ reactivity was investigated in RCM processes involving diethyldimethallyl malonates. Once again, an effect induced by the N-alkyl group was observed concerning the reactivity of the catalysts. A selectivity study was performed. As for ARCM processes forming trisubstituted olefins, the N-alkyl group also had an impact on the selectivity of the catalysts. This investigation was done with ARCM desymmetrization of meso-trienes.