Tesi sul tema "C-S bond formation"

In the following thesis, new methodologies towards harnessing C-S activation processes are documented. These methods utilise rhodium catalysis and are focused on the activation of aryl methyl sulfides. Chapter 1 provides an overview of the development of metal-catalysed C-S activation chemistry, with a focus on the catalytic systems, reagents and starting materials used to facilitate various C-C bond forming transformations. Chapter 2 describes a novel rhodium-catalysed cross-coupling reaction of aryl and alkyl terminal alkynes with simple aryl sulfides. This resulted in a Sonogashira-type transformation which exhibited orthogonality with traditional palladium catalysed Sonogashira chemistry. Chapter 3 documents a new catalytic system which allowed for the practical and efficient alkyne carbothiolation reactions of ketone-baring methyl sulfides. The carbothiolation products can be conveniently utilised in a one-pot three-component reaction to form highly substituted isoquinolines. Chapter 4 discusses the potential for future work. Chapter 5 presents the experimental data.

Aquetsa tesi descriu el treball realitzat amb reactius que contenen enllaços bor-sofre o bor-seleni. Aquest reactius s’han fet servir en reaccions de tioboració i selenoboració de substrats amb insaturacions conjugades a cetones o esters i en reaccions d’inserció amb grups diazo per a sintetitzar nous compostos organosulfurats i organoselenats. La tesi es divideix en quatre capítols. El primer d’ell és una breu introducció al compostos organosulfurats i organoselenats, parlant sobre les seves principals aplicacions i els mètodes per sintetitzar-los més representatius fins al moment. En aquest primer capítol també és parla de la síntesis dels reactius de bor-sofre i bor-seleni i les reaccions en les que s’han fet servir. El segon capítol parla de la reactivitat dels compostos de bor-sofre amb cetones i aldehids α,β-insaturats. S’ha observat que el propi grup carboxil és capaç d’activar el reactiu i fer entrar la unitat de sofre en la posició beta. El tercer capítol parla de la reacció amb triples enllaços conjugat a cetones i esters per sintetitzar vinil sulfats i vinil selenats. Aquesta mateixa reacció en presència d’una fosfina permet obtenir compostos anti-3,4-selenoborats que són precursors de compostos amb el grup seleni en la posició alfa. L’últim capítol parla sobre les reaccions d’inserció de compostos diazo en l’enllaç bor-sofre que permet obtenir molècules molt funcionalitzades amb grups Si, B, S i H que degut a les seves diferents propietats químiques poden continuar sent funcionalitzades per sintetizar una gran varitat de compostos orgànics.
Esta tesis describe el trabajo realizado con reactivos que contienen enlaces boro-azufre o boro-selenio. Estos reactivos se han usado en reacciones de tioboración y selenoboración de sustratos con insaturaciones conjugadas a cetonas o esteres y en reacciones de inserción con grupos diazo para sintetizar nuevos compuestos organosulfurados y organoselenados. La tesis se divide en cuatro capítulos. El primero es una breve introducción a los compuestos organosulfurados y organoselenados, hablando sobre sus principales aplicaciones y los métodos para sintetizarlos más representativos hasta el momento. En este primer capítulo también se presenta el método de síntesis de los reactivos de boro-azufre y boro-selenio y las reacciones en las que se han usado. El segundo capítulo habla de la reactividad de los compuestos de boro-azufre con cetonas y aldehídos α,β-insaturados. Se ha observado que el propio grupo carboxilo es capaz de activar el reactivo y hacer entrar la unidad de azufre en la posición beta. El tercer capítulo habla de la reacción con triples enlaces conjugado a cetonas y esters para sintetizar vinilo sulfatos y vinilo selenatos. Esta misma reacción en presencia de una fosfina permite obtener compuestos anti-3,4-selenoborats que son precursores de compuestos con el grupo selenio en la posición alfa. El último capítulo habla sobre las reacciones de inserción de compuestos diazo en el enlace boro-azufre que permite obtener moléculas muy funcionalizadas con los grupos Si, B, S y H que debido a sus diferentes propiedades químicas pueden continuar siendo funcionalizados.
This thesis describes the work done with reagents that contain links boron-sulphur or boron-selenium. These reagents have used in reactions of thioboration and selenoboration of substrates with unsaturation conjugated to ketones or esters and in reactions of insertion with diazo compounds to synthesize new organosulfides and organoselenides compounds. The thesis is divided in four chapters. The first is a brief introduction to the organosulfides and organoselenides compounds, reporting its main applications and its more representative methods of synthesis. The first chapter also reported the synthesis of the boron-sulphur and boron-selenium reagents and the reactions where they have been used. The second chapter is about the reactivity of the compounds of boron-sulphur with α,β-unsaturated ketones and aldehydes. It has observed that the carboxyl group is able to activate the B-S reagent and deliver the sulphur unit in the beta position. The third chapter shows the reactivity with triple bonds conjugated to ketones and esters to synthesise vinyl sulphates and vinyl selenates. The same reaction in presence of a phosphine allow to obtain anti-3,4-selenoborated compounds that they are precursors of compounds with the selenium moiety in the alpha position. The last chapter is about the insertion reactions of diazo compounds into the boron-sulphur bond that allow to obtain molecules very functionalized with groups Si, B, S and H than due to its different chemical behaviour can be further functionalized.

This thesis describes the catalysed addition of X-H bonds (X = S, O and N) to alkynes using a range of novel rhodium(I) and iridium(I) complexes containing hybrid bidentate phosphine-pyrazolyl, phosphine-imidazolyl and phosphine-N heterocyclic carbene (NHC) donor ligands. The synthesis of novel bidentate phosphine-pyrazolyl, phosphine-imidazolyl (P-N) and phosphine-NHC (PC) donor ligands and their cationic and neutral rhodium(I) and iridium(I) complexes [M(P N)(COD)]BPh4, [M(PC)(COD)]BPh4, [Ir(P-N)(CO)2]BPh4 and [M(P-N)(CO)Cl] were successfully performed. An unusual five coordinate iridium complex with phosphine-NHC ligands [Ir(PC)(COD)(CO)]BPh4 was also obtained. Seventeen single crystal X-ray structures of these new complexes were determined. A range of these novel rhodium and iridium complexes were effective as catalysts for the addition of thiophenol to a variety of alkynes. Iridium complexes were more effective than rhodium analogues. Cationic complexes were more effective than neutral complexes. Complexes with hybrid phosphine-nitrogen donor were more effective than complexes containing bidentate nitrogen donor ligands. An atom-economical, efficient method for the synthesis of cyclic acetals and bicyclic O,O-acetals was successfully developed based on the catalysed hydroalkoxylation. Readily prepared terminal and non-terminal alkyne diols were cyclised into bicyclic O,O-acetals in quantitative conversions in most cases. The efficiency of a range of rhodium and iridium complexes containing bidentate P-N and PC donor ligands as catalysts for the cyclisation of 4-pentyn-1-amine to 2-methyl-1-pyrroline varied significantly. The cationic iridium complexes with the bidentate phosphine-pyrazolyl ligands, [Ir(R2PyP)(COD)]BPh4 (2.39-2.42) were extremely efficient as catalysts for this transformation. Increasing the size of the substituent on or adjacent to the donor led to improvement in catalytic activity of the corresponding metal complexes. The mechanism of the catalysed hydroalkoxylation was proposed to proceed by the initial activation of the alkyne via ?? coordination to the metal centre. The ?? binding of both aliphatic and aromatic alkynes to [Ir(PyP)(CO)2]BPh4 (2.44) was observed by low temperature NMR and no reaction between 2.44 and alcohols was observed. In contrast, the facility in which thiol and amine oxidatively added to 2.44 led the proposal that in the hydrothiolation and hydroamination reaction, the catalytic cycle commences with the activation of the X-H bond (X = S, N) by an oxidative addition process.

This thesis describes the development of a new microwave-mediated methodology for C–S bond formation and the issues regarding scaling up heterocyclic transformations. Chapter 1 provides an overview on the current understanding of microwave-mediated synthesis and on the use of microwave technology in copper- and palladium-mediated synthesis. A separate part is dedicated to the current advancements in the use of flow reactors within the chemical community. Chapter 2 describes the application of the current batch and continuous flow technology for the scale-up of selected heterocyclic transformations, starting with the well known Bohlmann- Rahtz pyridine synthesis and moving to other reactions, including pyrimidine and Hantzsch dihydropyridine synthesis. Chapter 3 describes the development of a new methodology for the microwave-mediated C–S bond formation, starting from an investigation on the current available methods and moving to the application of new methodology to the synthesis of a library of compounds. Further application was found in the synthesis of a drug candidate with anti-ageing properties and in the synthesis of a new class of anti-HIV compounds.

Cette recherche visait à étudier les applications potentielles des complexes d'hydrure de Mg et de Ca soutenus par des ligands ß-diketiminate et amidinate pour la réduction des molécules de CO2. Les capacités catalytiques de ces complexes ont été explorées dans le contexte de l'hydroboration et de l'hydrosilylation du CO2. Dans la première partie de l'étude, nous avons examiné la réactivité des hydrures ß-diketiminato de Mg et de Ca avec le CO2. Il a été observé que le complexe d'hydrure de Mg incorporait rapidement le CO2, conduisant à la formation de divers intermédiaires avec différentes nucléarités. Cela implique l'insertion de la liaison Mg—H dans le CO2, ce qui entraîne la génération de groupements formate. Sous l'effet de la chaleur, des complexes de formiate hexamériques ont été formés par un mécanisme de "retournement de ligand", libérant les entraves stériques autour des centres métalliques. Pour les réactions à l'hydrure de Ca et au CO2, l'analyse RMN in situ a été principalement réalisée. En outre, un nouveau complexe amidinate dihydride de Mg a été synthétisé avec succès et a réagi avec du CO2 pour donner un produit unique de complexe formate Mg dimérique, contrairement à l'échafaudage ß-diketiminate, où plusieurs espèces de formate ont été détectées. La deuxième partie de la recherche s'est concentrée sur l'hydroboration catalytique du CO2 à l'aide de complexes d'hydrures alcalino-terreux. En particulier, le système à base de Ca a démontré une grande efficacité dans la production de la réduction à quatre électrons du CO2 ou du produit BBA. Il s'agit du premier exemple d'utilisation de composés hydrides de Mg et de Ca pour catalyser l'hydroboration du CO2, produisant sélectivement le produit BBA. Le BBA généré in situ a ensuite été utilisé comme réactif de transfert de méthylène dans des réactions de condensation avec des thiols, ce qui a entraîné la formation de nouveaux composés hémithioacétals stables [RS—CH2—OBR2] dans des conditions douces et neutres. L'activation des composés hémithioacétals a été réalisée dans des conditions acides, conduisant à la formation de dithioacétals et d'hémithioaminals. La condensation du deuxième fragment OBR2 avec des amines secondaires, qui agissent comme des nucléophiles plus puissants, a abouti à la génération de sulfures d'aryle et de méthyle [RS—CH2—NR2]. Dans la dernière section, nous avons étudié l'hydrosilylation en tandem du CO2 en utilisant divers hydrosilanes en combinaison avec des complexes d'hydrures à base de [Ae] et l'acide de Lewis B(C6F5)3 comme catalyseurs. Cette recherche a élargi les études précédentes sur l'hydrosilylation du CO2 médiée par le Mg et a introduit le premier exemple d'hydrosilylation du CO2 catalysée par le Ca avec des hydrosilanes. L'efficacité de la réduction du CO2 en CH4 ou en bis(silyl)acétal [H2C(Ph3SiO)2] ou en BSA dépend de la nature des silanes et des encombrements stériques autour de la liaison Si—H du substrat. Le choix du catalyseur [Ae] a également influencé de manière significative la vitesse globale de la réaction. En outre, les analyses d'Eyring et d'Arrhenius ont permis de mieux comprendre les paramètres d'activation de la réduction du CO2 par certains catalyseurs, révélant que cette réaction est principalement régie par une contribution entropique. En résumé, cette recherche a démontré la réactivité des complexes d'hydrure de Mg et de Ca pour la réduction du CO2 et a exploré leurs applications dans les réactions d'hydroboration et d'hydrosilylation. Les recherches futures pourraient explorer les possibilités mécanistiques, les différences cinétiques et la réactivité des complexes d'hydrures métalliques du groupe 2 avec le monoxyde de carbone pour l'homologation du CO
This research aimed to investigate the potential applications of Mg and Ca hydride complexes supported by ß-diketiminate and amidinate ligands for the reduction of CO2 molecules. The catalytic abilities of these complexes were explored in the context of hydroboration and hydrosilylation of CO2. In the first part of the study, we examined the reactivity of ß-diketiminato Mg and Ca hydrides with CO2. It was observed that the Mg hydride complex rapidly incorporated CO2, leading to the formation of various intermediates with different nuclearities. This involved the insertion of Mg—H bond into CO2, resulting in the generation of formate moieties. Under heat, hexameric formate complexes were formed through a "ligand flip" mechanism, releasing steric hindrances around the metal centers. For Ca hydride and CO2 reactions, in situ NMR analysis was mainly conducted. Additionally, a novel Mg amidinate dihydride complex was successfully synthesized and reacted with CO2 to yield a unique single product of dimeric formate Mg complex, in contrast to the ß-diketiminate scaffold, where several formate species were detected. The second part of the research focused on the catalytic hydroboration of CO2 using alkaline-earth hydride complexes. In particular, the Ca-based system demonstrated high efficiency in the production of the four-electron reduction of CO2 or BBA product. This was the first example of using Mg and Ca hydride compounds to catalyze the hydroboration of CO2, selectively producing the BBA product. The in situ generated BBA was further used as a methylene transfer reagent in condensation reactions with thiols, resulting in the formation of novel stable hemithioacetal [RS—CH2—OBR2] compounds under mild and neutral conditions. Activation of the hemithioacetal compounds was achieved under acidic conditions, leading to the formation of dithioacetals and hemithioaminals. The condensation of the second OBR2 fragment with secondary amines, which act as stronger nucleophiles, resulted in the generation of aryl methyl sulfides [RS—CH2—NR2]. In the final section, we investigated the tandem hydrosilylation of CO2 using various hydrosilanes in combination with [Ae]-based hydride complexes and Lewis acid B(C6F5)3 as catalysts. This research expanded on previous studies of Mg-mediated hydrosilylation of CO2 and introduced the first example of Ca-catalyzed CO2 hydrosilylation with hydrosilanes. The effectiveness of reducing CO2 to CH4 or bis(silyl)acetal [H2C(Ph3SiO)2] or BSA depended on the nature of the silanes and the steric hindrances around the substrate Si—H bond. The choice of [Ae] catalyst also significantly influenced the overall reaction rate. Furthermore, Eyring and Arrhenius analyses provided insight into the activation parameters for reducing CO2 by certain catalysts, revealing that this reaction is primarily governed by an entropic contribution. In summary, this research has demonstrated the reactivity of Mg and Ca hydride complexes for CO2 reduction and explored their applications in hydroboration and hydrosilylation reactions. Future investigations may explore mechanistic possibilities, kinetic differences, and the reactivity of group 2 metal hydride complexes with carbon monoxide for CO homologation

This work is foremost a study of various palladium-bearing N-heterocyclic carbenes complexes and their catalytic potential to form C-N bonds. Both alkyl amination and aryl amination are considered. Further elucidation on the mechanism of such catalytic activity is investigated. The viability of alkyl amination using palladium complexes bearing the ligands, ITMe, 1,2,3,4- tetramethylimidazol-2-ylidene, and ICy, 1,3- bis-cyclohexylimidazol-2-ylidene, as catalysts, is investigated. This includes the synthesis of [Pd(ITMe)(neopentyl)Cl]2,[Pd(ITMe)2(neopentyl)Cl], [Pd(ITMe)(neopentyl)(tbutylamine)Cl], [Pd(ITMe)(neopentyl)(hexylamine)Cl], with successful elimination of the alkyl-amination reaction product in low yield from the latter complex. [Pd(ICy)(neopentyl)Cl]2, [Pd(ICy)2(neopentyl)Cl] are also isolated. Unsuccessful attempts were made to vary the electronic properties of the complexes by replacing the amine with a hydrazine. Work was also done on indirect alkylation using tBuLi which led to a new method for synthesis of [Pd(ItBu)2] and novel complex, [Pd(ItBu)Cl3. ItBuH] (ItBu = 1,3- bis-tertbutylimidazol-2-ylidene). Aryl amination catalysed by complexes of palladium bearing the ligand, ITMe, is considered. This includes an improved synthesis of [Pd(ITMe)2] and synthesis of [Pd(ITMe)2(anisole)Cl]. Unsuccessful attempts at the elucidation of the mechanism of [Pd(ITMe)2(anisole)] formation led to the unexpected formation of [Pd(ITMe)2(SiMe3)(Si(SiMe3)3)] and [Pd(ITMe)2(SiMe3)2]. Aryl amination with using [Pd(ITMe)2(SiMe3)2] led to two aryl amination products, 4-ortho-methoxyphenyl morpholine as well as the expected para isomer. The use of complexes [Pd(ItBu)2] and [Pd(SIPr)2] (SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) in C-S bond formation was explored. Addition of mesityl magnesium bromide to Pd(1,5-COD)Cl2 led to addition of mesityl substrate across 1,5-COD double bond and the addition of ITMe formed the Heck cycle intermediate [Pd(8-mesityl-1,4,5-η3 – C8H12)X2] (X=Cl, Br). Addition of 4-tolyl magnesium chloride resulting in the formation of Pd(ItBu)2(tolyl)Cl via an indirect route.

碩士
國立中正大學
化學所
96
Recently, cross-coupling reactions (including C－S bond, C－O bond and C－N bond formation) attracted great attention, because of their versatile possibilities of biological, pharmaceutical and material applications, thus we focus on C－S bond formation in this thesis. Copper catalyzed cross-coupling reaction is a remarkable and economic method of C－S bond formation, and we prepared two different copper complexes as the catalysts of cross-coupling reactions. We performed the cross-coupling reactions with three conditions: (1) aryl halides and thiophenols were dissolved in toluene and heated in a 120℃ oil bath under nitrogen atmosphere; the highest yield was 91.8%. (2) aryl halides and thiophenols were dissolved in water and heated to 80℃ under air; the reactions were nearly inactive. (3) phenylboronic acids and disulfides were dissolved in water/1,4-dioxane (1:2) and heated to 100℃ under air; the highest yield was 73.7%.

碩士
國立中興大學
化學系所
106
In the first part of this thesis, we report a general copper-catalyzed cross-coupling of thiols with aryl chlorides by using N,N''-dialkyl oxalic diamide (L5) as the ligand. Both aryl- and alkyl thiols can be coupled with unactivated aryl chlorides to give the desired products in good yields for the first time. Furthermore, this system features broad substrate scope and good tolerance of functional groups. Importantly, the oxalic diamides are stable and can be prepared easily from commercially available cheap starting materials. The second part of this thesis, application of this copper-catalyzed cross-coupling of 2,4-dimethylyhiophenol with 1,2-diiobenzene by using N,N''-dialkyl oxalic diamide (L5) as the ligand has been described for the synthesis of antidepressant Vortioxetine.

The worldwide reliance on fossil fuels for energy and petrochemicals poses a massive environmental hazard. Furthermore, many chemical processes rely on precious metals that have low abundance on Earth and are threatened. As the world population grows rapidly, these factors pose an increasing threat to our planet and new chemical processes are needed that employ earth-abundant catalysts and alternative chemical currencies such as light and electricity derived from renewable sources.

Chapter 2 discusses an in-depth mechanistic study of the photoinduced, copper-mediated cross-coupling of aryl thiols with aryl halides. This reaction employs light energy and an earth-abundant metal to achieve bond formation through a pathway distinct from that of thermal reactions. In particular, I focus on the stoichiometric photochemistry and subsequent reactivity of a [Cu^I(SAr)₂]^– complex (Ar = 2,6-dimethylphenyl). A broad array of experimental techniques furnish data consistent with a pathway in which a photoexcited [Cu^I(SAr)₂]^-* complex undergoes SET to generate a Cu^II species and an aryl radical, which then couple through an in-cage radical recombination.

Chapter 3 discusses the surface attachment of a P₃^BFe complex to a carbon electrode, and the electrochemical generation of ammonia from N₂ by the surface-appended species (P₃^BFe = tris-phosphinoborane). Ammonia production is achieved industrially by the combination of N₂ and H₂, the latter of which is derived from methane with concomitant production of CO₂. Alternative chemical processes, such as the use of energy derived from electricity, are vital for the decreasing the carbon footprint of ammonia production. Synthetic modification of a previously-reported P₃^BFe complex by addition of three pyrene substituents onto the catalyst backbone allows non-covalent attachment onto a graphite surface. The resulting functionalized electrode shows good stability towards iron desorption under highly reducing conditions, and produces 1.4 equiv NH₃ per iron site. The data presented provide the first demonstration of electrochemical nitrogen fixation by a molecular complex appended to an electrode.

碩士
國立中興大學
化學系所
106
In the first part of this thesis, we report a convenient and efficient approach via copper-catalyzed thiolation of imidazo[1,2‐a]pyridines with sulfur powder, the reaction condition is under ligand-free and solvent-free, 14 examples were reported up to 98% yield. In the second part of this thesis, we reported a palladium-catalyzed decarbonylation C-S cross coupling reaction to convert thioester to thioether. In the present protocol a variety of electron-withdrawing and electron-donating group have been used and they can all proceed well in this protocol, even the alky group can get the result up to 50% yield. This process demonstrates a novel and efficient strategy to synthesize thioether.

碩士
國立中興大學
化學系所
106
In the first part of this thesis, we achieve a simple and elegant method for dithioacetalization of aldehyde using blue LEDs irradiation under photochemical reaction. The salient features of this method are broad substrate scope and good tolerance of electron donating and withdrawing group, metal free and solvent free conditions. It is noteworthy that our present protocol is eco-friendly in nature and we will develop LEDs promoting reaction in future green chemistry avenues. In the second part of this thesis, we achieve a simple method for thiol ether formation of aryl amines and thiols using blue LEDs irradiation under photochemical reaction. This project is metal free, solvent free and eco-friendly in nature.