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1
Zhang, Chi Ph D. Massachusetts Institute of Technology Department of Chemistry. "Cysteine arylation." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/112448.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references.
Proteins are the chemical and biological foundation of life. The longstanding goals of chemical biology are to understand the structure and function of proteins and to use these biomolecules for applications in chemistry, biology, medicine, and material science. To achieve such goals, highly efficient, selective, and robust chemical reactions are desired to modify proteins. For decades, cysteine-based reactions with maleimides and alkyl halides are the primary methods for selectively tagging proteins with fluorescent dyes, affinity and radio labels, drug molecules, and polymers and nanocomposites. These traditional reactions generate sulfur-sp³ carbon bonds between the cysteine thiol and the labeling reagents. The goal of this thesis is to develop new cysteine arylation reactions to generate sulfur-sp² carbon bonds on proteins. These reactions are used to make novel peptide and protein therapeutics. Two mechanistically complementary approaches are developed to arylate cysteine thiol. First, through a nucleophilic aromatic substitution (SNAr) mechanism, fluorinated aromatic reagents are used for the regioselective arylation of a single cysteine in the presence of many. An enzyme-tag pair (glutathione S-transferase (GST) and glutathione (GSH)) and a self-labeling short peptide (Phe-Cys-Pro-Phe, the 7-clamp) are respectively developed to recognize the fluorinated aromatic reagents and to promote the arylation reaction in aqueous solution. The second approach utilizes organometallic palladium reagents to chemoselectively install electron-neutral and electron-rich aryls on cysteine thiols. These cysteine arylation reactions are applied to the synthesis of macrocyclic peptides and antibody-drug conjugates (ADCs). Long unprotected macrocyclic peptides up to forty residues are efficiently synthesized using the GST enzyme. Using bispalladium reagents, macrocyclic peptides bearing aryl linkers are synthesized via crosslinking of two cysteine thiols. [pi]-Clamp antibodies enable a one-step synthesis of site-specific antibody-drug conjugates to selectively kill cancer cells. Organometallic palladium reagents are used to synthesize linker-free ADCs where the drug molecules are directly linked to cysteine thiols in antibodies.
by Chi Zhang.
Ph. D.
2
Corrie, Thomas James Alexander. "Intramolecular direct arylation." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28820.
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The research conducted for this thesis has led to the development of an intramolecular gold-catalysed direct arylation protocol whereby tethered arenes and aryltrimethylsilanes are coupled (Scheme 1). In Chapter 1, the key synthetic and mechanistic studies that have ultimately led to the conception of this project are introduced. In Chapter 2, the substrate scope of intramolecular direct arylation is assessed. The reaction tolerates a wide range of substrates with tether lengths between one and five units (containing C, N and O) generating 5- to 9- membered rings. Substrates that lead to 5-membered rings (1 → 2) can tolerate a broad electronic range of substituents and proceed under the mildest reaction conditions (≤ 1 mol% catalyst, room temperature) and with excellent yields. A smaller collection of examples is demonstrated for the cyclisation to 6- and 7- membered rings (3 → 4, 5 → 6), but no heating is required and good yields are maintained throughout the series. The synthetically challenging synthesis of 8- and 9- membered rings (7 → 8, 9 → 10) is successful, albeit with slightly more forcing conditions (4 mol%, up to 50 °C). The methodology was subsequently applied in the successful 10-step synthesis of natural product allocolchicine 11. In Chapter 3, the operative reaction mechanism is elucidated. Reaction monitoring techniques allowed for the detailed study of linear free energy relationships (LFERs) and kinetic isotope effects (KIEs), which in turn allowed for deduction of the reaction turnover-limiting step (TLS) and thus the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diarylgold(III) species. The mechanistic investigation led to the observation of complex kinetic profiles for specific substrates. The origin of these unusual effects is the focus of Chapter 4. By combining experiment with kinetic simulation, an off-cycle catalyst inhibition pathway was identified and the understanding of this process allowed for a re-optimisation of reaction conditions. In Chapter 5, the general kinetic parameters that could govern any domino reaction combining inter- and intramolecular direct arylation are deduced through kinetic analysis and simulation of hypothetical systems. The results of the kinetic analysis were proved experimentally through the successful combination of intra- and intermolecular gold-catalysed direct arylation. The products of intramolecular cyclisation 2, generated in-situ, are demonstrated to couple with intermolecular aryltrimethylsilanes 12, resulting in a rapid increase in molecular complexity from simple substrates in one pot.
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Turner, Gemma L. "Direct arylation of thiazoles." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3188.
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An introduction to the thiazole ring system is presented together with a detailed, but non-exhaustive review of the rapidly emerging area of palladium-mediated directed arylation. The direct arylation of thiazole is also discussed together with our attempts to improve the established methods. A high-yielding, mild protocol has been developed for the functionalisation of the most electron-rich carbon-hydrogen bonds in a number of heterocyclic ring systems, this represents the first example of a C-H activation reaction being accomplished in aqueous media and allows access to a diverse range of functionalised aryl heterocycles. In addition, work towards functionalisation of the thiazole C4 position is described. A number of different approaches are discussed and our endeavors are recorded.
4
Evans, Ethan Daniel. "Long peptides for cysteine arylation." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/118258.
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Thesis: Ph. D. in Biological Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2018.Cataloged from PDF version of thesis.
Includes bibliographical references.
Biological reactivity is typically carried out by large enzymes. There are few examples of reactive, amino-acid-based polymers shorter than 100 residues in length. Of those that do exist, the majority are very short tags (<15 amino acids). Here, we attempted to first discover peptides roughly 30 amino acids in length that promote a nucleophilic aromatic substitution reaction and then understand the features and properties that emerge. Using the 20 canonical amino acids, there are 20³⁰ different peptide sequences possible in this size realm. To isolate a portion of the space capable of reacting with a perfluoroaromatic small molecule, we performed an mRNA display selection. This uncovered a host of putative reactive peptides with little similarity at the sequence level. The primary isolate (MP01) displayed reactivity confirming the success of the selection and was sensitive to truncation and denaturants. We next set out to study the reactivity of an expanded portion of the isolated peptides and look for shared structural or mechanistic themes. Analyzing an additional 26 peptides with almost no sequence similarity, we discovered diverse levels of reactivity along with sequences capable of undergoing multiple reactions. Using computational structure prediction and circular dichroism spectroscopy we discovered that both mixed alpha-helical and random coil as well as beta-sheet-based reactive peptides existed. Studying their structural properties revealed that many of the peptides undergo significant structural alterations upon reaction with the perfluoroaromatic. Returning to MP01 we studied its mutational tolerance as well as its structural and mechanistic properties. Alanine scanning mutagenesis revealed mutations that diminished reactivity in addition to others that improved its function. Computational structure prediction suggested a mixed helical and random coil structure. Combining the beneficial mutations with insights from modeling initiated an iterative process that ultimately led to a 100-fold improved reaction rate. This sequence (MP01-Gen4) was six mutations different from MPG 1 and was more reactive than any other peptide discovered. MP01-Gen4 displayed flexibility and lacked a defined three-dimensional structure, however, it was significantly more helical than its progenitor. This sequence also displayed structural alterations, becoming more helical in the presence of its small molecule reaction partner, when either covalently reacted or noncovalently interacting.
by Ethan Daniel Evans.
Ph. D. in Biological Chemistry
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Fournier, Anne. "Intramolecular arylation of lithiated carbamates." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/intramolecular-arylation-of-lithiated-carbamates(165caa71-c229-4db3-a2e3-a77b097e5ef9).html.
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This thesis describes research carried out on the synthesis of tertiary alcohols or derivatives by N to C aryl/vinyl migration in lithiated carbamates. Section II.1 describes the first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer as an illustration of the methodology. It has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of alpha-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement in contrast with related ureas. Modelling work to establish the origin of this stereodivergent behaviour is reported in Section II.2. This also reports in-situ IR experiments providing evidence of the mechanistic pathway of the rearrangement of an O-benzyl-N-aryl carbamate. The scope of the N to C aryl migration in other stabilised organolithiums is shown in section II.3. The rearrangement is now addressed in more systematic manner, thus allowing the alpha-arylation of O-allyl and O-propargylcarbamates (by alpha-deprotonation) and O-vinylcarbamates (by alpha-deprotonation) to be achieved in good yields but with poor stereoselectivity. Section II.4 goes on to show that enol carbamates derived from aromatic or alpha,beta-unsaturated compounds and bearing an N-aryl substituent undergo carbolithiation by nucleophilic attack at the alpha position of the enol double bond. The resulting carbamate-stabilised allylic, propargylic or benzylic organolithium rearranges with N to C migration of the N-aryl substitutent, creating a quaternary carbon alpha to O. The products may be easily hydrolysed to generate multiply branched tertiary alcohols in good to moderate yields in a one-pot tandem reaction. Finally, Section II.5 proves that the rearrangement in lithiated carbamates can be extended to N to C vinyl transfer.
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Sävmarker, Jonas. "Palladium-Catalyzed Carbonylation and Arylation Reactions." Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-167720.
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Palladium-catalyzed reactions have found widespread use in contemporary organic chemistry due to their impressive range of functional group tolerance and high chemo- and regioselectivity. The pioneering contributions to the development of the Pd-catalyzed C-C bond forming cross-coupling reaction were rewarded with the Nobel Prize in Chemistry in 2010. Today, this is a rapidly growing field, and the development of novel methods, as well as the theoretical understanding of the various processes involved are of immense importance for continued progress in this field. The aim of the work presented in this thesis was to develop novel palladium(0)- and palladium(II)-catalyzed reactions. The work involved in achieving this aim led to the development of a Mo(CO)6-mediated carbonylative Stille cross coupling reaction for the preparation of various deoxybenzoins. The protocol utilized convenient gas-free conditions to facilitate the carbonylative coupling of benzyl bromides and chlorides with aryl and heteroaryl stannanes. Mo(CO)6-assisted conditions were then used in the development of a general protocol suitable for the aminocarbonylation of aryl triflates. Both electron-poor and electron-rich triflates were coupled with primary, secondary and aryl amines. In addition, DMAP was found to be a beneficial additive when using sterically hindered or poorly nucleophilic amines. An efficient and convenient method for the synthesis of styrenes from arylboranes was developed, employing the relatively inexpensive vinyl acetate as the ethene source under Pd(II)-catalyzed conditions. The reaction mechanism was studied using ESI-MS, and a plausible catalytic cycle was proposed. A method for the oxidative Heck reaction employing aryltrifluoroborates and aryl MIDA boronates was also developed. Electron-rich and electron-poor olefins were regioselectively arylated under microwave-assisted conditions. Various arylboron species were identified in an ongoing reaction using ESI-MS. Further investigations led to the development of a direct method for the synthesis of arylamidines from aryltrifluoroborates and cyanamides. Under Pd(II)-catalyzed conditions it was possible to insert the aryl into primary, secondary and tertiary cyanamides. Finally, a desulfitative method for the synthesis of aryl ketones was developed. A variety of aryl sulfinates were effectively inserted into alkyl- and aryl nitriles. The mechanism was further investigated using ESI-MS and a plausible catalytic cycle was proposed.
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Leblanc, Mélissa. "Synthèse d'allocolchicinoides via une arylation directe." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27264.
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Le motif biaryle tricyclique est un motif important en chimie médicinale et est présent dans une grande variété de produits naturels. Les chimistes ont développé au cours des années différentes méthodologies pour les synthétiser. La majorité des réactions impliquent l'utilisation d'un aryle fonctionnalisé par un organometallique et réagissant avec un halogénure d'aryle. Récemment, notre laboratoire rapportait une nouvelle procédure permettant de synthétiser des biaryles tricycliques d'une façon efficace et rapide. Cette nouvelle méthodologie est une réaction d'arylation directe catalysée par le palladium, par laquelle la partie organometallique a été remplacée par un hydrogène. Ainsi, un halogénure d'aryle peut maintenant réagir avec un aryle simple pour former le biaryle désiré. Cette réaction d'arylation directe a été récemment étendue à la formation de biaryles tricycliques contenant un cycle à sept membres. Elle peut s'effectuer à partir des chlorures ou des bromures d'aryles. Cette méthodologie a donc été employée dans la synthèse formelle de l'allocolchicine et d'un de ses analogues.
Pour effectuer la réaction d'arylation directe d'une façon efficace, il a été détermine que la proportion ligand/palladium jouait un rôle primordial dans la quantité de produit hydrodéhalogène obtenue. De plus, le choix du ligand, par ses propriétés stériques et électroniques, a un impact sur le pourcentage de conversion obtenu lors de la cyclisation. Les ligands riches en électrons, tels que 2-(dicyclohexylphosphino)-2'- N,N-dimethylaminobiphenyle, sont les ligands qui ont fourni les meilleurs résultats.
Par ailleurs, concernant la formation du centre chiral retrouvé dans l'allocolchicine, deux stratégies de synthèse ont été explorées, soit un couplage asymétrique direct et une réduction enantiosélective. Finalement, l'alcool chiral a été obtenu à l'aide d'une réduction enantiosélective d'une cétone via un réactif de bore, dérivé d'un mélange équimolaire de pinène et de 9-BBN.
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Douglas, Gayle Elizabeth. "Investigations into direct N-arylation reactions." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/23026/.
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This thesis details investigations and the optimisation of N-arylation reactions using preciousmetal- free conditions. It is an important motif in several pharmaceutical and agrochemical molecules. In 1965 Bock et al described the use of concentrated sulfuric acid and acetic acid as the solvent in a modified version of the Hofmann-Lӧffler-Freytag to carry out direct amination of aromatics via N-haloamines.1 The first section looks at the UV irradiation chemistry where we utilised N-halo species which under photolytic conditions form the aminium radicals. Several examples of tetrahydroquinolines being synthesised in flow have been carried out. Investigations into amination of electron-deficient heterocycles such as pyridines were also investigated. Unfortunately, no N-arylation was observed under the various conditions trialled. Similar investigations have been carried out into the photolysis of N-chloroamides with varying degrees of chain length and position of the amide. Under neutral conditions in the presence of a Lewis acid some success in N-arylation reactions has been observed. In the second section the use of iron(II) salts has been investigated towards the N-arylation reaction via the aminium radial generated from the N-halo species. A variety of substrates containing electron-poor and electron-rich aromatic rings have been synthesised under these conditions. This methodology has been expanded to include an iron salt variant of the work with examples of intramolecular and intermolecular direct N-arylation described. Using our methodology some simple aromatics and the drug naproxen have now been aminated successfully. The use of hydroxylamines as alternative precursors to the aminium radical has also been investigated with some success in the synthesis of various substrates.
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Williamson, Alice Elizabeth. "Novel methods for catalytic asymmetric arylation." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610600.
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Niwa, Takashi. "Studies on Palladium-Catalyzed Benzylic Arylation." 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/77959.
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Kyoto University (京都大学)0048
新制・課程博士
博士(工学)
甲第14583号
工博第3051号
新制||工||1454(附属図書館)
26935
UT51-2009-D295
京都大学大学院工学研究科材料化学専攻
(主査)教授 大嶌 幸一郎, 教授 檜山 爲次郎, 教授 松原 誠二郎
学位規則第4条第1項該当
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Blaskovits, Terence. "Une étude computationnelle de la polymérisation par (hétéro)arylation directe : [A Computational Study of Direct (Hetero)arylation Polymerization]." Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/34540.
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En comparaison avec d’autres techniques de couplage-croisé adaptées à la synthèse de polymères conjugués, la polymérisation par (hétéro)arylation directe (PHAD) s’avère avantageuse d’une perspective industrielle et environnementale. En effet, elle permet d’éviter l’utilisation d’agents de transmétallation nécessaires aux méthodes classiques de polymérisation. La réaction de PHAD exploite l’activation de liens aromatiques carbone-hydrogène (C–H) pour une synthèse efficace de polymères conjugués avec une excellente économie d’atomes. La réaction d’(hétéro)arylation directe permet la formation d’un lien entre deux atomes de carbone d’hybridation sp2 à partir d’un lien C–H via l’état de transition de la métallation-déprotonation concertée (CMD). La majorité des polymères conjugués utilisés en électronique organique contient des unités de répétition à base de thiophène. Cet hétérocycle, possédant des propriétés électroniques et stériques désirables, sont fonctionnalisés avec des groupes donneurs ou accepteurs d’électrons, ainsi qu’avec des chaînes aliphatiques à des fins de solubilité. Cependant, l’utilisation du motif thiophène peut mener à des défauts structuraux dans la chaîne polymère puisqu’elle comporte plusieurs liens C–H activables en PHAD. Si un lien C-H non-désiré (en position β du motif thiophène) est activé plutôt que le lien en position α, un défaut en β peut alors être incorporé de manière covalente dans la structure polymérique résultante. La présence de défauts en β mène à une perturbation de la conjugaison du polymère et de l’organisation du matériau à l’état solide, des facteurs qui peuvent réduire les performances en dispositifs d’électronique organique. Étant donné l’omniprésence du motif thiophène au sein des polymères conjugués et sa sélectivité parfois problématique, une étude computationnelle du mécanisme de l’arylation directe sur des unités thiophènes modèles a été entreprise dans le cadre de ce projet. En utilisant la théorie de la fonctionnelle de la densité et le cluster couplé, les barrières d’activation pour l’état de transition de la CMD de plusieurs substrats modèles ont été calculées et analysées par la méthode de la distorsion-interaction. L’effet activant d’un halogène sur les liens C–H adjacents à celui-ci a été étudié. Les résultats permettront de guider la conception de monomères pour la réalisation de matériaux régioréguliers par PHAD.The direct (hetero)arylation polymerization (DHAP) reaction harnesses the single-step activation and arylation of aromatic carbon-hydrogen bonds for the efficient synthesis of conjugated polymers. By avoiding the need for transmetalating agents used in other polymerization techniques, the number of synthesis steps is reduced, the need for expensive and often unstable reagents is minimized and the production of toxic organometallic by-products is eliminated. These factors contribute to a reaction which is more favourable than traditional methods for the preparation of conjugated polymers from an industrial and an environmental perspective. Most high-performing conjugated polymers for organic electronic applications contain thiophene-based repeating units. These heterocycles possess desirable electronic features and are easily functionalized with electron-accepting or -donating substituents or solubilizing side-chains to tune their electronic and physical properties. However, the issue has arisen over the selectivity of the concerted metalation-deprotonation (CMD) transition state, the key step of the direct arylation mechanism which determines the selectivity of C–H bond activation. There are multiple reactive C–H bonds on thiophene monomers, and if the undesired bond (the “Cβ–H” bond) were to be activated, it would generate a β-defect in the resulting polymer. This may lead to a disruption in both the π-conjugation of the polymer and the supramolecular organization of the material in the solid state, factors which can contribute to reduced performance in organic electronic devices. Given the ubiquity of thiophene-based units in conjugated polymers and the assumed issues regarding selectivity, we used computational techniques to study the direct arylation mechanism on model thiophene substrates possessing various electronic features. Using density functional theory and coupled-cluster methods, activation barriers for the CMD transition states of various C–H bonds were calculated and analyzed using the distortion/interaction model. The activating effect of a halide on thiophene was also studied. The results suggest that there are inherent features of selectivity for electron-rich or electron-poor thiophenes, and that the location of the halogen greatly influences coupling selectivity by activating the undesirable Cβ–H bond. These findings could guide the design of monomers amenable to high-selectivity DHAP protocols.
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Lafrance, Marc. "Development of new palladium-catalyzed arylation reactions." E-theses uOttawa (Restricted to University of Ottawa), 2008. https://login.proxy.bib.uottawa.ca/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:NR41635.
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Liu, Haiyang. "Arylation of fibres to achieve disperse dyeability." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436409.
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Holden, Catherine. "Transition metal-free arylation and heterocycle synthesis." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/transition-metalfree-arylation-and-heterocycle-synthesis(4ecff18c-6cf9-4dfe-a874-1d83601c94d3).html.
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Arenes are ubiquitous motifs in both naturally occurring and synthetic functional organic molecules. The investigation of metal-free methodology for the installation of these motifs is important for sustainable development and the discovery of new modes of reactivity. Chapter 1. The preparation of halogenated phenoxathin 10,10 dioxides was ascertained to proceed through fluoride-induced decomposition and subsequent recombination of two molecules of the o-trimethylsilyl(aryl) triflate aryne precursors. Chapter 2. A new mild and metal-free methodology for the transition metal-free preparation of 2-amino biaryls using the benzyne intermediate was established. This proceeds via a desulfonative Truce-Smiles rearrangement of an aryl anion in the key bond-forming step. Chapter 3. The electron-poor S-aryl sulfonamides developed in chapter 2 were explored as reagents for metal-free 1,1- and 1,2-carbonamination. Asymmetric catalysis was also investigated for the preparation of enantioenriched alpha,alpha-disubstituted aryl glycine derivatives. Chapter 4. Some organocatalytic methods for the vicarious nucleophilic substitution of hydrogen were investigated to expand the remit of this classical arylation mechanism.
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Tetlow, Daniel John. "α-Arylation of lithiated N-allyl ureas." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/alphaarylation-of-lithiated-nallyl-ureas(c901ad80-be95-4257-8b31-f5363e59d544).html.
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The synthesis of amines bearing an adjacent quaternary stereocentre is challenging. Work within our group has demonstrated that the intramolecular transfer of an aryl group within a lithiated benzylic urea is possible. Subsequent cleavage of this urea moiety allows the synthesis of chiral aryl amines bearing quaternary stereocentres. This thesis details investigations into the lithiation of allylic and vinylic ureas. A sequential transformation of allyl ureas into diarylallyl ureas has been developed, a reaction that can be carried out enantioselectively using chiral lithium amides. Deprotection of the urea allows for the isolation of amines bearing highly substituted centres. It has been shown that the use of the acid-labile vinylic protecting groups allows the corresponding Cbz protected diarylallyl amines to be synthesised. Investigations have demonstrated that these analogues can be converted into otherwise synthetically challenging diarylglycine derivatives. During these investigations it has also been shown that carbolithiation of vinyl ureas is possible. The ureas formed from this tandem β-alkylation/α-arylation sequence can then be converted to their highly substituted amine counterparts in good yields. A range of allylic ureas has been investigated; their synthesis and reactivity upon lithiation are discussed within this thesis.
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Aspin, Samuel. "Arylation migratoire C(sp3)-H d'énolates d'esters." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10298.
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La fonctionnalisation C(sp3)-H catalysée par des métaux de transitions, ouvre de nombreuses perspectives en synthèse organique, permettant des voies d'accès plus économes en atomes, et en étapes à des molécules à forte valeur ajoutée. Dans cette optique, une méthode efficace permettant l'arylation des liaisons C(sp3)-H en position α d'un groupement attracteur, plus communément appelée α -arylation a récemment fait l'objet d'une attention toute particulière de la part de la communauté scientifique. Le travail détaillé dans ce manuscrit décrit les dernières avancées de cette méthodologie, ainsi qu'une variante «β-arylation » développée au laboratoire qui constitue une évolution significative dans le domaine de l'arylation regiosélective des liaisons C(sp3)-H non activées. Dans le cadre de ce projet de thèse nous nous sommes efforcés de développer cette nouvelle réaction que nous avons pu optimiser pour l'étendre à une famille plus étendue de substrats de type amino-esters. Dans la continuité de ce travail nous avons réalisé la première réaction d'arylation migratoire sélective d'amino-esters pouvant aller jusqu'à la position η d'une chaîne alkyle linéaire. Enfin, dans le but d'accéder à de nouvelles molécules à plus haute valeur ajoutée, nous avons pu appliquer notre méthodologie aux acetals de cétènes silylés permettant de dépasser certaines limitations du système existant. Dans ce cas précis, des conditions plus douces (sans base forte) ont permis l'arylation de substrats dits sensibles et par extension la synthèse de lactones fonctionnaliséesThe transition metal catalysed functionalization of C(sp3)-H bonds unlocks numerous perspectives within organic synthesis in terms of atom economical access routes to otherwise difficult to synthesise molecules. One efficient method to exact such transformations involves the exploitation of an activated C-H bond situated adjacent to an activating electron withdrawing group, allowing facile insertion of a transition metal catalyst species and subsequent functionalization with a new species (normally an aryl group). This strategy is generally termed ‘α-functionalization’. The work detailed within this manuscript describes a diversion from the classic, and well documented α-functionalization reaction, in which rearrangement steps within the catalytic cycle give rise to β- and more remote substrate functionalization. The first new methodology to be described involves a fundamental extension to the in-house developed β-arylation reaction, in which, through careful substrate and ligand choice, this methodology could be applied to achieve the functionalization of simple ester enolates in remote γ- to η - positions. The developed strategy allowed the synthesis of a small range of interesting homophenylalanine analogues, and higher homologues. The second methodology to be described involves a necessary modified protocol for the β-arylation reaction, in which silyl ketene acetals were exploited as mild metal-enolate surrogates, allowing the coupling of base-sensitive substrates. The previously described reaction scope has been extended in terms of both the electrophile and nucleophile coupling partners through the development of mild reaction conditions, which subsequently allowed application of several products towards the synthesis of lactones
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Caron, Laurence. "Direct arylation of aromatic rings using palladium catalysis." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28232.
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The first section illustrates the novel route to access the biphenyl motif. Starting from simple materials, nitroarenes and aryl halides, we are able to obtain different cross-coupled products in good to moderate yields using palladium as a catalyst. The optimization of the reaction conditions as well as the various biaryl motifs obtained are described.*
The second section summarizes our efforts towards the development of universal reaction conditions that can be used for the arylation of a wide range of heterocycles. Although direct arylation products are available in the literature, no broadly accessible method is available yet. The heterocycles described are limited to azoles and the various motifs obtained are illustrated.*
*Please refer to dissertation for diagrams.
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Smith, Charlotte Louise. "α-Arylation as an entry to cytisine variants." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658203.
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The body of research in this thesis investigates the use of the Gallagher 3rd generation synthesis to make cytisine (i) and core variants of cytisine (ii) and (iii). A crucial step in the synthesis is the reduction of the lactam carbonyl, which can either be attempted before or after cyclisation. It was found that attempts to reduce the lactam carbonyl after cyclisation (iv) were unsuccessful, whereas reduction before cyclisation (v) was not reproducible. Alternative methodology to allow for the synthesis of a wider range of variants using a-arylation was developed. It was shown that the conditions used needed to be tailored to the system, making test systems not representative. By using a reduced number of equivalents of bromide in the reaction, diarylation, the main by-product isolated from a-arylation, could be supressed and only monoarylation (vi) was observed.
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Yagoubi, Myriam. "Synthesis of heterocycles via palladium-catalysed direct arylation." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:e1206b3a-b9e8-4371-a94c-da3bc04c116e.
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Chapter 1 is a brief review on some of the recents developments in palladium-catalysed C-H functionalisation chemistry. The synthesis and functionalisation of heterocycles using these methodologies was particularly emphasised. Chapter 2 presents our efforts to identify a new catalytic system to promote the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds for the formation of benzofurans. Dihydrobenzofurans were obtained efficiently under mild conditions in the presence of Pd(OAc)₂, X-Phos and K₂CO₃ in DMA at 80 °C and a subsequent one-pot isomerisation under acidic conditions afforded the desired benzofurans. A new strategy has also provided access to more complex benzofurans by functionalisation of the exocyclic alkene isomer in both a chiral and achiral manner. In Chapter 3, mechanistic studies were performed on the benzofuran formation reaction. The analysis of substituent effects on the aromatic ring is in accordance with an electrophilic aromatic substitution mechanism (SEAr); however, the existence of both intra and intermolecular kinetic isotope effects suggest a SE3 type pathway rather than a pure SEAr. In Chapter 4, the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds was further extended to the synthesis of six-membered heterocycles by direct arylation of alkenyl bromide derivatives in the presence of Pd(OAc)₂, dppf and K₂CO₃ in DMA at 120 °C. The synthetic utility of this methodology was exemplified by the synthesis of substituted isoquinolines in six steps. Moreover, we have applied our methodology to the direct arylation of sulfonamides, leading to an interesting synthesis of widely used sultams. Both these new routes are currently being investigated and should provide access to a variety of differently substituted cyclic sulfonamides and isoquinolines. Finally, Chapter 5 presents a new strategy for the synthesis of benzo[b]furan was briefly investigated. It consists in consecutive Tsuji-Trost and C-H functionalisation reactions. This methodology requires simpler and more versatile substrates, allowing access to various heteroaromatics in a single step. We successfully proved the viability of this reaction through the synthesis of a range of benzofurans in modest yields. To our knowledge, this is the first example of a single palladium catalyst performing these different reactions in tandem in a simple procedure.
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Sollert, Carina. "New Arylation Strategies Based on Organomain Group Reactivity." Doctoral thesis, Uppsala universitet, Institutionen för kemi - BMC, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328750.
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The work in this thesis describes the development of new heteroarylation methodology based on transition metal-catalysed C-H functionalisation and the properties of organomain group compounds. The underlying reaction mechanisms and reactivity patterns of the (hetero)arene substrates are also investigated. The selective C2-H arylation indoles, which are key pharmaceutically-relevant units, was achieved using N-pyrimidyl directing groups, RuII catalysis and arylboronic acids as the coupling reagents (paper I). The use of this set of conditions enabled a remarkable functional group tolerance, highlighted by the preservation of halide substituents on both coupling partners. Mechanistic experiments suggest that cleavage of the C2-H bond occurs through an electrophilic aromatic substitution type pathway. The dehydrogenative C2-H silylation of unprotected gramine and tryptamine alkaloids and other related heteroarenes using hydrosilanes under Ru0 catalysis is described in paper II. The protocol does not require protecting groups and undirected C2-H silylation of heteroarenes is possible at higher temperatures. Significantly, H/D-exchange studies revealed deuterium incorporation at the C4 and C7 positions of the indole unit, apart from C2-H silylation. This study represents the first account of C4-H activation using an electron-rich metal catalyst. Paper III describes an unexpected and profound influence of boronate substituents on the regioselectivity of aryne trapping reactions. The boronates may be introduced easily to the backbone of established fluoride-activated precursors via Ir-catalysed C-H functionalisation. Optimisation and mechanistic studies on the unprecedented level of regioselectivity control these substituents permit using external additives is presented.
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Tait, Michael Buchanan. "α-Arylation of lithiated allylic and vinylic ureas." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/aarylation-of-lithiated-allylic-and-vinylic-ureas(9403f676-5c28-49db-9b00-dc41a8977d16).html.
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Chiral amines are widespread in naturally occurring and synthetic bioactive molecules. However, it remains challenging to synthesise these molecules in an enantiopure form. Investigations within our group have shown that treatment of vinylic ureas with organolithium reagents results in an umpolung addition of the organolithium, followed by N to C aryl migration of the lithiated intermediate. This thesis details investigations into developing an enantioselective version of this reaction through the use of the chiral ligands (−)-sparteine and the (+)-sparteine surrogate. The enantioenriched ureas are easily transformed into the corresponding a-tertiary amines. Use of the different chiral ligands allows access to either enantiomer of the rearranged urea. Further work has centred on the application of this methodology towards cyclic substrates; with a view to synthesising a-tertiary cyclic diaryl amines. Studies have shown that treatment of vinylic ureas bearing cyclic substituents with a number of different organolithium reagents successfully produce the desired rearranged ureas, with complete diastereoselectivity. Subsequent solvolysis of these ureas yields hindered cyclic a-tertiary amines in good yields. During these investigations it has been shown that allylic ureas undergo a rearrangement to the least sterically hindered side of the cyclic urea. This allows for fine tuning of the migration reaction depending on where the double bond is positioned in the molecule. A range of vinylic and allylic ureas, including substrates with interesting pharmaceutical properties, have been investigated. Their synthesis and reactivities upon lithiation are discussed within this thesis.
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Salcedo-Serna, Maria-Angela. "Synthèse de 1,4-benzodiazépines-2,5-diones et benzoxazole-isoindolinones par séquences : réaction d'Ugi / cyclisations intramoléculaires : travaux préliminaires pour une nouvelle synthèse de la phytosphingosine." Paris 11, 2007. http://www.theses.fr/2007PA112190.
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Le projet de thèse s’est articulé en trois parties. Dans les deux premières parties, nous avons développé des synthèses rapides d’hétérocycles facilement variables et très fonctionnalisés, via des séquences de réaction d’Ugi/cyclisation intramoléculaire. Nous avons pu mettre au point deux séquences générales permettant d’obtenir, en peu d’étapes à partir de produits commerciaux ou facilement accessibles, des 1,4-benzodiazépine-2,5-diones et des benzoxazole-isoindolinones. Les 1,4-benzodiazépine-2,5-diones ont été obtenues grâce une séquence domino N-arylation/couplage croisée palladocatalysé. L’intervention d’un composé macropalladacycle peptidique bis-σ-arylpalladium a pu être, en partie, confirmé. D’une autre côte, une réaction de O-arylation catalysée au cuivre suivi par une réaction d’α-arylation catalysée au palladium nous a permis d’avoir accès au motif benzoxales-isoindolines. Ces séquences sont convergentes et permettent une variation aisée des substituant en quatre points de la molécule. En fin, nous nous sommes intéressés à la synthèse totale de la phytosphingosine. Nous avons réussi, en quelques étapes, à préparer l’intermédiaire clé de la synthèse envisagéeThe thesis is articulated into three parts. In the first two parts, we have developed the rapid synthesis of easily functionalized heterocyclics, based on an Ugi reaction/intramolecular cyclization sequence. We were able to develop two sequences respectively leading to 1,4-benzodiazepin-2,5-diones and benzoxazole-isoindolin-1-ones from commercial or readily accessible products. The 1,4-benzodiazepin-2,5-diones were obtained through a palladium catalyzed N-arylation/cross coupling domino sequence. Isolation and crystallization of peptide macropalladacycle has allowed us to bring mechanistic insides for this transformation. In the second part, a copper catalyzed O-arylation followed by a palladium catalyzed α-arylation gave access to benzoxazole-isoindolin-1-ones. These sequences are converging and allowed easy modification of substituants in four points of the molecule. Finally, we have been interested in the total synthesis of phytosphingosine. In a few steps, we succeeded to prepare the key intermediate of the synthesis
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Gilligan, Ruth Elaine. "Copper-catalyzed C-H arylation : development of new methodology and its application to the total synthesis of staurosporinone." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607788.
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Whipp, Christopher J. "Part 1: The Direct Arylation of Azine N-Oxides with Aryl Triflates Part 2: The Site-Selective Direct Arylation of Substituted Indoles." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28792.
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Part 1: The Direct Arylation of Azine N -Oxides with Aryl Triflates. Two sets of conditions for the palladium-catalyzed direct arylation of azine N-oxides with aryl triflates have been developed. Using palladium(II) acetate, a trialkylphosphine ligand, a carbonate base and pivalic acid, both mono- and diarylated azine N-oxides could be synthesized in good to excellent yields.*
The reaction regioselectivity was examined for 3-substituted pyridine N-oxides, with arylation at C2 being favoured. The methodology was applied to the efficient formal synthesis of a biologically active diaryl pyridine.
Part 2: The Site-Selective Direct Arylation of Substituted Indoles. Initial studies into the site selectivity of the direct arylation reaction were conducted. Several competition studies were performed using various methodologies to determine the selectivity, if any, between two arenes capable of undergoing direct arylation. It was found that selectivity was greatest when competition was between one electron-rich and one electron-poor arene.*
From these results a substituted indole was synthesized and subsequently derivatized at three different positions. It was demonstrated that site selectivity on a complex molecule could be achieved through careful selection of reaction conditions.
*Please refer to dissertation for diagrams.
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Jepson, David. "Copper- and nickel-catalysed N-arylation of cyanate salts." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590419.
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The transition metal-catalysed N-arylation of cyanate salts represents an atom-economical approach to the synthesis of aryl isocyanates and isocyanate derivatives, which are commonly produced using hazardous reagents such as phosgene or azides. This thesis describes the development of copper and nickel-catalysed methodologies for the cross-coupling of aryl halides to commercially available cyanate salts, where reactions performed in the presence of various nucleophiles provide access to a wide range of useful products through intermolecular or intramolecular trapping. Firstly, an effective copper-catalysed system was developed using ligand screening and extensive optimisation work, allowing for the synthesis of aromatic carbamates, ureas and various heterocyclic compounds from aryl iodides. Though no isocyanates were isolated or detected during these experiments, this approach provided a novel, efficient method for the synthesis of these compounds. The 'reaction conditions were also used in the synthesis of commercial drug molecule Sorafenib, providing phosgene-free access to this valuable product. A nickel-catalysed variant was also developed, allowing for the synthesis of aromatic carbamates and ureas from inexpensive aryl bromides and chlorides, though issues of poor reproducibility meant that the reaction was of limited synthetic value. In the process of these investigations, a novel arylnickel(Il) cyanate complex was synthesised and its reactivity investigated.
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Long, Philip. "Rhodium-phosphinite catalysts for the ortho-arylation of phenols." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529840.
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Simoneti, Marco. "Novel approaches for Ru-promoted C-H arylation methods." Thesis, Queen Mary, University of London, 2016. http://qmro.qmul.ac.uk/xmlui/handle/123456789/24249.
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The development of new procedures for the production of biologically and industrially relevant compounds still remains a big challenge in chemistry. The biaryl motif is ubiquitous among a wide range of compounds of industrial importance. For example, the biaryl skeleton is found in molecular switches and motors, agrochemicals or medicines such as antifungal, anticancer, antibiotics, anti-inflammatory treatments. These properties make the biaryl functionality a highly desirable synthetic target, for both commercial and research purposes. In this context, C-H arylation has been acknowledged as a useful alternative to traditional cross-couplings, replacing the organometallic coupling partner by a non-prefunctionalised substrate in the reaction with a haloarene. Approaches for the development of Ru-catalysed C-H arylation methodologies are presented herein. The introduction provides a general overview about different strategies employed in metalcatalysed direct C-H arylation methods. The rational behind selectivity and reactivity are also thoroughly discussed. The second chapter describes studies on the C-H activation of perfluorinated arenes by Ru(II)-species. The synthesis of unprecedented aryl rutyhenium complexes and mechanistic considerations on the metalation of the arene are presented. In the last part of the second chapter the development of a bis-cationic rutehium(II) complex able to catalyse direct C-H arylation of electron-poor arenes with bromoarenes in the absence of any directing group is described. A complete mechanistic analysis, along with the scope of the methodology, is therefore given.
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Gatland, Alice Elizabeth. "Palladium-catalysed enolate arylation in the synthesis of isoquinolines." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:f106760d-2375-4d56-81b2-faa6ee96cabc.
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Chapter 1. Introduction Scientific background on the development of homogeneous palladium-catalysed cross coupling reactions, focusing on the α-arylation reaction of enolates and its application to the synthesis of heteroaromatic compounds. The classical syntheses of isoquinolines are discussed, followed by an account of modern methods for their synthesis, including the recent α-arylation-based methodology developed by the Donohoe group. Chapter 2. Results and Discussion 2.1 Studies towards the development of a palladium-catalysed, C–H activation-based α arylation reaction of ketones, resulting in a C–H bromination/α-arylation sequence for the synthesis of isoquinolines and isoquinoline N-oxides. 2.2 The one-pot, four component coupling of a ketone, an acetal protected ortho-bromobenzaldehyde or ketone, an electrophile, and an ammonia source is described. This protocol, which ultimately provides C4 functionalised isoquinolines, is later extended to a novel α,α heterodiarylation protocol to furnish C4-aryl isoquinolines. 2.3 It is shown that the synthesis of 3 aminoisoquinolines can be achieved via the α arylation of nitriles. tert-Butyl cyanoacetate can act as a substitute for primary alkyl nitriles, with sequential α-arylation, in situ functionalisation, decarboxylation and cyclisation reactions provide C4 functionalised 3 aminoisoquinolines. 2.4 The synthetic utility of the α arylation based methodology for isoquinoline synthesis is exemplified by the total synthesis of the alkaloid berberine in 68% yield over five steps. This is followed by syntheses of pseudocoptisine, palmatine, dehydrocorydaline, and an unnatural fluorine containing analogue, in yields of 46%, 73%, 60% and 37%, respectively. 2.5 Finally, preliminary investigations demonstrate the utility of palladium-catalysed enolate arylation in the synthesis of β-carbolines.
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Lindstedt, Erik. "Metal-Free O- and C-Arylation with Diaryliodonium Salts." Doctoral thesis, Stockholms universitet, Institutionen för organisk kemi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-140944.
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This thesis concerns the development of metal-free applications using diaryliodonium salts. The first project describes an arylation protocol of allylic and benzylic alcohols in aqueous media. The method proceeds under mild conditions and the ether products were obtained in moderate to good yields. The methodology was also expanded to include arylation of phenols, giving diaryl ethers in good to excellent yields. In the second project, an arylation method that included a wider range of aliphatic alcohols was developed. The scope of accessible alkyl aryl ethers was studied and included a comparative study of phenylation and nitrophenylation of various alcohols. Finally, a formal metal-free synthesis of butoxycain was performed, illustrating the applicability of the developed method. The third project focused on the limitations and side reactions occurring in Chapter 2 and 3. First, an approach to access symmetric diaryl ethers via arylation of hydroxide was presented. This reaction gave rise to a number of side products, which we hypothesized to originate from aryne-type intermediates. A mechanism for the formation of these side products was suggested, supported by trapping and deuterium labeling experiments. Oxidation of the alcohol to the corresponding ketone was also observed and the mechanism of this interesting side reaction was investigated. The latter was suggested to proceed via an intramolecular oxidation without the involvement of radicals or arynes. The fourth project covers a method to synthesize highly sterically congested alkyl aryl ethers via arylation of tertiary alcohols using diaryliodonium salts. The method displayed a broad scope of tertiary alcohols and was also suitable for fluorinated alcohols. The final project detailed in this thesis deals with C-arylation with diaryliodonium salts, showcasing nitroalkanes as well as a nitro ester as suitable nucleophiles for metal-free arylation.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.
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Tlili, Anis. "Arylation de nucléophiles catalysés par des complexes de cuivre." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2011. http://www.theses.fr/2011ENCM0010.
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Au cours de cette thèse, plusieurs nouvelles méthodes d'arylation de nucléophile (oxygéné, azoté et carboné) ont été mises au point ainsi qu'une étude mécanistique. Dans le cadre du projet ANR, nous avons réalisé des travaux dans ce domaine dans le laboratoire du Dr Anny Jutand à L'ENS Paris. D'un point de vue général, nous pouvons donc dire que nos méthodes se situent bien en phase avec les critères de la réglementation européenne visant à diminuer l'impact des produits chimiques sur l'environnement (REACH) par la recherche de nouvelles voies de synthèse moins toxiques et moins polluantes. Travaux en cours et perspectives : Par rapport aux réactions faisant intervenir des catalyseurs au palladium, celles impliquant le cuivre ont très peu été étudiées du point de vue de leur mécanisme. Les premiers travaux concernant le mécanisme de l'arylation de nucléophiles catalysé au cuivre ont débuté depuis seulement quelques années et ont conduit à environ une dizaine de publications. Malgré quelques avancées significatives, beaucoup reste à faireIn this thesis, several new methods of nucleophilic arylation (oxygen, nitrogen and carbon) were developed and a mechanistic study. As part of the ANR project, we have carried out work in this field in the laboratory of Dr. Anny Jutand at ENS Paris. From a general point of view we can say that our methods are well in line with the requirements of European regulations to reduce the impact of environmental chemicals (REACH) by the search for new synthetic routes less toxic and less polluting. Work in Progress and prospects : Compared to reactions involving palladium catalysts, those involving copper have been studied very little in terms of their mechanism. Early work on the mechanism of arylation of nucleophiles catalyzed copper began last few years and led to about a dozen publications. Despite some significant advances, much remains to be done
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Grolleau, Jérémie. "Synthèse de nouveaux semi-conducteurs organiques par arylation directe." Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0029/document.
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Les recherches sur le photovoltaïque organique depuis une dizaine d’année ont permis une constante progression de l’efficacité des cellules solaires. Plusieurs groupes de recherche ont amorcé une réflexion sur les procédés de synthèse qui permettraient de limiter les déchets. Ainsi le couplage par arylation directe qui évite l’utilisation de dérivés organométalliques a émergé comme alternative au couplage organométallique classique. Une première partie est consacrée à l’étude méthodologique du couplage par arylation directe de la triphénylamine avec des dérivés du thiophène-2- carboxaldéhyde substitués en C3 et C4 par des groupements électro-accepteurs et électro-donneurs. Ce motif de base permet l’accès à trois séries de petites molécules par simple condensation. Des cellules photovoltaïques atteignant des rendements de photo-conversion de 3% en cellules bicouches, ont été obtenues. Dans une deuxième partie, la polymérisation par arylation directe sur des monomères du thiophène substitué par des groupements nitriles comme accepteur et des groupements alcoxy ou thioalkyl comme donneur conduit en une seule étape à une nouvelle famille de polymères conjugués. Ces polymères ont été utilisés comme matériaux donneurs et accepteur dans des cellules. Enfin en dernière partie, un travail exploratoire sur les propriétés d’émission de dérivés du benzofurane a été entrepris. Des réactions de condensation de Knoevenagel ont été développées pour obtenir toute une série de dérivés contenant l’unité cyano-vinylbenzofurane. La plupart des composés présente une forte émission à l’état solideResearch on organic photovoltaics over a decade allowed a steadily increasing in the efficiency of solar cells. Several research groups have begun a reflection on the synthesis processes to limit wastes. Thus the direct arylation coupling which avoids the use of organometallic compounds, has emerged as an example of green reaction. The first part is devoted to the methodological study of direct arylation of bromotriphenylamine with thiophene-2-carboxaldehyde derivatives substituted in C3 and C4 by electron-withdrawing groups and electron-donor groups. This basic pattern allows access to three small molecules by condensation. Photovoltaic cells reaching photoconversion efficiencies of 3% were obtained. In the second part, the polymerization by direct arylation of sustituted thiophene monomers by nitrile groups as the acceptor and by alkoxy or thioalkyl as the donor led in one step to a novel family of conjugated polymers having donor and acceptor groups alternately. Solar cells were made with the polymers as donors or as acceptors materials. Finally, in the last part, exploratory work on the emission properties of benzofuran derivatives have been made. Knoevenagel condensations have been developed for a range of compounds containing the cyano-vinylbenzofuran unit. Most compounds have high emission in the solid state
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Mas-Roselló, Josep. "C-arylation and alkenylation of α-amino acid derivatives." Thesis, University of Bristol, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738542.
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Skhiri, Aymen. "Réactivité des chlorures de benzènesulfonyle pour l'accès à des hétéroarènes et alcènes arylés via des réactions pallado-catalysées." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S080.
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Au cours de cette thèse, nous nous sommes intéressés à la synthèse d’hétérocycles arylés via l’activation de liaisons sp2 C-H d’hétéroaromatiques et à la synthèse d’alcènes arylés halo-substitués catalysée par le palladium. Les produits obtenus sont considérés comme des briques moléculaires, intéressantes pour les biochimistes, ainsi que pour la préparation de matériaux. Le système catalytique Pd(MeCN)2Cl2/Li2CO3/dioxane permet l’accès direct à une grande variété de molécules arylées à partir d’hétéroarènes ou d’alcènes et de chlorures de benzènesulfonyle. Nous avons mis au point une méthode permettant l’arylation directe en position β de sélénophènes à partir de sélénophènes et de chlorures de benzènesulfonyle. Nous avons également montré que l’utilisation de chlorures de benzènesulfonyle (poly)halogénés permet de synthétiser par des réactions pallado-catalysées des hétéroarènes arylés, des stilbènes ou des cinnamates (poly)halo-substituésIn this thesis we have been interested in the synthesis of arylated heterocycles via the activation of sp2 C-H bonds of heteroaromatics and to the synthesis of halo-substituted arylated alkenes using palladium-catalysis. The products obtained are considered to be molecular bricks which are of interest to biochemists as well as to the preparation of materials. The catalyst system Pd(MeCN)2Cl2/Li2CO3/dioxane allows the direct access to a wide variety of arylated molecules from heteroarenes or alkenes and benzenesulfonyl chlorides. We have developed a method for the direct β-arylation of selenophenes from selenophenes and benzenesulfonyl chlorides. We have also shown that the use of (poly)halogenated benzenesulfonyl chlorides makes it possible to synthesize, by Pd-catalyzed reactions, (poly)halo-substituted arylated heteroarenes, stilbenes or cinnamates
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Hillgren, J. M. ikael. "Synthesis of quarternary asymmetric centres using novel enolate arylation chemistry." Thesis, University of Leeds, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509834.
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Brandt, Jochen Robert. "Site-selective copper-catalyzed arylation of aniline and phenol derivatives." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609610.
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Maxwell, Justin Michael. "Carbon Dioxide-Mediated C–H Arylation of Biologically-Relevant Amines." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1576249564349573.
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Duvall, Bridget Rebecca. "Efforts toward (+)-7-deoxypancratistatin featuring a palladium catalyzed allylic arylation." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/2336.
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Thesis (M.S.)--University of Maryland, College Park, 2005.Thesis research directed by: Dept. of Chemistry and Biochemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Mingat, Gaelle. "Tertiary thiols via stereospecific α-arylation of lithiated allylic thiocarbamates." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/tertiary-thiols-via-stereospecific-alphaarylation-of-lithiated-allylic-thiocarbamates(91e495f6-9924-4e96-8c23-50e84ea205ac).html.
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This thesis describes the work carried out on the lithiation and rearrangement of N-aryl- and N-vinyl allylic thiocarbamates, with the aim of preparing a wide range of versatile tertiary thiols. The synthesis of the racemic allylic starting materials has been achieved through in situ [3,3]-sigmatropic rearrangement of O-allylthiocarbamates to their S-counterparts (II.A). The enantioselective version relies either on asymmetric metal catalysis (achiral substrates) or stereospecificity (enantiopure substrates) in the [3,3]-sigmatropic rearrangement. Lithiation followed by N to C aryl migration proceeds in generally good to excellent yields, with both electron-poor and electron-rich rings. The scope and the influence of various substituents at Cα or on the allylic double bond are presented in Section II.B.1. Section II.B.2 proposes a mechanistic pathway and details NMR studies carried out to get structural data in the α-thioallyllithium intermediates. Investigations of the stereospecificity of the rearrangement show that most rings migrate without loss of enantioenrichment in substrates bearing an unsubstituted allylic double bond (II.B.3.a). Complete enantiospecificity with all rings has been achieved in thiocarbamates bearing a cyclohexyl-substituted double bond (II.B.3.b). Section II.C reports the results obtained in the N to C transfer of non-aromatic groups. Excellent enantiospecificities have been achieved in the migration of a vinyl substituent, although yields remain moderate. Higher yields can be obtained but they come along with lower enantiomeric ratios. Section II.D details the transformations undertaken in the rearranged tertiary allylic thiocarbamates. A wide range of tertiary thiols has been obtained with good to excellent yields. Functionalisation of the allylic double bond in these hindered substrates was not straightforward. Eventually, ring-closing metathesis in S-allyl sulfides allows the preparation of biologically interesting 2,5-dihydrothiophenes bearing a highly enantioenriched quaternary centre. Finally, evidence for retentive aryl migration in allylic thiocarbamates is outlined in Section II.E. Circular dichroism experiments were carried out in the derivatised 2,5-dihydrothiophenes and compared with predictions obtained via DFT calculations for both enantiomers of a model compound. The absolute configuration of the 2,5-dihydrothiophenes and their tertiary thiocarbamate precursors has been unambiguously established, confirming a retentive pathway in both aryl and vinyl migrations.
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Seidl, Thomas Ludwig. "The Preparation of Diaryliodonium Salts for Application in Arylation Chemistry." PDXScholar, 2018. https://pdxscholar.library.pdx.edu/open_access_etds/4238.
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Diaryliodonium salts offer potential as novel reagents for arylation chemistry. An overall goal and successful outcome of this work has been to further understanding of diaryliodonium salt chemistry by developing practical methods that enable chemists more convenient access to these reagents, for the purpose of reaction development. To this end a robust and convenient preparation method has been developed and resulted in novel commercially available diaryliodonium salts. The remainder of the work described, has focused on understanding the parameters important to diaryliodonium mediated arylation and has resulted in a solid framework that multiple future development efforts can build upon.
A strategy adopted throughout this work was to use multivariate methodologies such as Design of Experiments (DoE). Applicable chapters show the results of optimization studies that were carried out using DoE, during the course of this work. Additionally, the desire to further realize the potential that DoE has to offer inspired of a search for parameters to study fundamental reactivity. Chapter 2 details the development of a practical diaryliodonium salt synthesis that is convenient, facile, and economical. A detailed procedure is also included and was drafted to the requirements for publication in the journal Organic Synthesis. Finally, limitations and future directions of the method are discussed. Chapter 3 describes studies aimed at understanding the role of the counter anion; a very practical counter anion screening method is presented. Future directions are discussed and include detailed characterization of diaryliodonium salts by NMR. Chapter 3 also describes a practical, scalable, and rapid salt exchange method developed during this work. Chapter 4 describes the results obtained in studying an azidation reaction via solubility parameters. All Supporting Information, including characterization data and experimental details, are provided in Chapter 5.
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Lainer, Bruno. "A multicatalytic approach to enantio-, and diastereoselective arylation of alcohols." Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAF080.
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Les groupements alcooliques sont présents dans une grande diversité de produits chimiques fins précieux issus de la nature et de la synthèse, c'est pourquoi les méthodes permettant leur diversification structurelle sont recherchées. Cependant, la modification de la structure des alcools à certaines positions non réactives, même avec l'aide de la catalyse, reste un défi ou nécessite des procédures multi-étapes fastidieuses et souvent coûteuses. Récemment, une attention accrue a été accordée à la multicatalyse, qui combine plusieurs catalyseurs au sein d'un même système, ce qui permet de découvrir des réactivités auparavant inaccessibles ou d'accroître l'efficacité globale des transformations en plusieurs étapes. Les méthodes décrites ici permettent l'α- et la β-arylation diastéréo- et énantiosélective d'alcools. En combinant des catalyseurs à base de Ru et de Pd, il est possible de réaliser une β-arylation énantiosélective (et diastéréodivergente dans le cas d'alcools portant déjà des stéréocentres) sans précédent d'alcools primaires. En outre, dans le cadre d'une catalyse relais séquentielle, il est possible d'obtenir des alcools benzyliques secondaires enrichis enantioénergie à partir de divers produits de départ disponibles, tels que des alcools primaires ou des alcools portant une double liaison. Dans l'ensemble, ces protocoles démontrent le potentiel de la multicatalyse en tant qu'outil synthétique pour diversifier les alcools. Dans un contexte plus large, cette thèse ouvre la voie à la conception de nouvelles stratégies et méthodes multicatalytiques pour une synthèse efficaceAlcohol moieties are present in a great diversity of valuable fine chemicals from nature and synthesis, therefore methods enabling their structural diversification are sought after. However, modifying the structure of alcohols at certain unreactive positions, even with the aid of catalysis, remains a challenge or requires tedious often wasteful multistep procedures. Recently, increased attention has been paid to multicatalysis, which combines multiple catalysts within one system, enabling the discovery of previously inaccessible reactivities or increasing the overall efficiency of multistep transformations. Described within are methods which enable the diastereo-, and enantioselective α-, and β-arylation of alcohols. By combining Ru- and Pd-based catalysts the unprecedented, enantioselective (and diastereodivergent in the case of alcohols already bearing stereocenters) β-arylation of primary alcohols can be carried out. Also, under sequential relay catalysis enantioenriched secondary benzylic alcohols can be obtained from a variety of available starting materials, such as primary alcohols, or alcohols bearing a double bond. Overall, these protocols demonstrate the potential of multicatalysis as a synthetic tool for diversifying alcohols. In a broader context, this thesis sets the stage for devising novel, multicatalytic strategies and methods for efficient synthesis
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Sagnes, Charlène. "Synthèse, marquage TEP et validation de nouveaux radiopharmaceutiques des récepteurs sérotoninergiques 5-HT6 et 5-HT7." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10272.
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La sérotonine ou 5-hydroxytryptamine (5-HT) est un neurotransmetteur impliqué dans un grand nombre de fonctions physiologiques (thermorégulation, mémoire, sommeil, humeur…). La pluralité des troubles engendrés par un dysfonctionnement sérotoninergique s’explique par le grand nombre de récepteurs associés (5-HT1 à 5-HT7, eux-mêmes divisés en sous-groupes). Parmi eux, les récepteurs 5-HT6 et 5-HT7 sont les derniers à avoir été identifiés. A ce jour bien que leurs rôles biologiques restent méconnus, ils sembleraient être impliqués dans certaines pathologies psychiatriques (dépression, anxiété, schizophrénie…) et pourraient représenter de nouvelles cibles thérapeutiques. Ainsi, dans un premier temps, une étude bibliographique présentera l’ensemble des récepteurs sérotoninergiques et détaillera les travaux relatant des 5-HT6 et 5-HT7. La seconde partie sera consacrée à la synthèse de ligands potentiels des 5-HT7 et à l’étude de relation structure-activité associée. L’exemplification d’une réaction de C2-arylation d’indole inédite catalysée par le cuivre fera l’objet de la troisième partie. La quatrième partie sera consacrée à la synthèse de ligands antagonistes connus des récepteurs 5-HT6 afin de les employer comme radiotraceurs potentiels. Cette partie exposera également la synthèse de ligands potentiels inédits de ces récepteurs. Enfin, les premiers résultats de radiosynthèse et de leur application TEP (Tomographie à Emission de Positons) seront exposésSerotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter involved in many physiological functions (thermoregulation, memory, sleep, mood ...). The plurality of disorders caused by a serotonergic dysfunction due to the large number of receptors involved (5-HT1 to 5-HT7, divided themselves into sub-groups). Among them, the 5-HT6 and 5-HT7 are the last to be identified. To date, although their biological roles remain unknown, they appear to be involved in some psychiatric disorders (depression, anxiety, schizophrenia ...) and could represent new therapeutic targets. Thus, initially, a bibliographic study will present all the serotonin receptors and detail work on the 5-HT6 and 5-HT7. The second part will be devoted to the synthesis of potential ligands of 5-HT7 and the study of structure-related activity. The exemplification of a reaction of C2-arylation of indole catalyzed by copper will be the third party. The fourth part will be devoted to the synthesis of antagonists ligands known of 5-HT6 receptors in order to use them as potential radiotracers. This part also describes the synthesis of novel potential ligands of these receptors. Finally, preliminary results of radiosynthesis and their application PET (Positron Emission Tomography) are exposed
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Bielawski, Marcin. "Diaryliodonium Salts : Development of Synthetic Methodologies and α-Arylation of Enolates." Doctoral thesis, Stockholms universitet, Institutionen för organisk kemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-54738.
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This thesis describes novel reaction protocols for the synthesis of diaryliodonium salts and also provides an insight to the mechanism of α-arylation of carbonyl compounds with diaryliodonium salts. The first chapter gives a general introduction to the field of hypervalent iodine chemistry, mainly focusing on recent developments and applications of diaryliodonium salts. Chapter two describes the synthesis of electron-rich to electron-poor diaryliodonium triflates, in moderate to excellent yields from a range of arenes and iodoarenes. In chapter three, it is described that molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. A large scale synthesis of bis(4-tert-butylphenyl)iodonium triflate is also described, controlled and verified by an external research group, further demonstrating the reliability of this methodology. The fourth chapter describes the development of a sequential one-pot synthesis of diaryliodonium salts from aryl iodides and boronic acids, furnishing symmetric and unsymmetric, electron-rich to electron-poor diaryliodonium tetrafluoroborates in moderate to excellent yields. This method was developed to overcome the regiochemical limitations imposed by the reaction mechanism in the protocols described in the preceding chapters. Chapter five describes a one-pot synthesis of heteroaromatic iodonium salts under similar conditions described in chapter two. The final chapter describes the reaction of enolates with chiral diaryliodonium salts or together with a phase transfer catalyst yielding racemic products. DFT calculations were performed, which revealed a low lying energy transition state (TS) between intermediates, which is believed to be responsible for the lack of selectivity observed in the experimental work. It is also proposed that a [2,3] rearrangement is preferred over a [1,2] rearrangement in the α-arylation of carbonyl compounds. The synthetic methodology described in this thesis is the most generally applicable, efficient and high-yielding to date for the synthesis of diaryliodonium salts, making these reagents readily available for various applications in synthesis.
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Hao, Xinyu. "Amidomonophosphane-Rodium(I) Complex Catalyzed Asymmetric Arylation of N-Phosphinoyl aldimine." 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/124041.
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Mo, Jun. "Palladium catalyzed heck arylation of electron-rich olefins by aryl halides." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433729.
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Toh, Qiao Yan. "Organocatalysis in total synthesis and C-H bond arylation of aldehydes." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648134.
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Morin, Pierre-Olivier. "Développement de la polymérisation par (hétéro)arylation directe pour l'électronique organique." Doctoral thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27087.
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L’électronique organique suscite un intérêt grandissant en recherche grâce aux nouvelles possibilités qu’elle offre pour faciliter l’intégration de dispositifs électroniques dans nos vies. Grâce à elle, il est possible d’envisager des produits légers, flexibles et peu coûteux à produire. Les classes majeures de dispositifs étudiées sont les cellules photovoltaïques organiques (CPO) et les transistors organiques à effet de champ (TOEC). Dans les dernières années, une attention particulière a été portée sur les méthodes de polymérisation des matériaux organiques entrant dans la fabrication de ces dispositifs. La polymérisation par (hétéro)arylation directe (PHAD) catalysée au Pd offre une synthèse sans dérivé organométallique utilisant simplement un lien C-H aromatique, ce qui facilite la purification, diminue le nombre d’étapes et rend possible la production de matériaux à plus faible coût. De plus, la PHAD permet la préparation de matériaux qui était difficile, voire impossible, à obtenir auparavant. Cependant, l’inconvénient majeur de la PHAD reste sa limitation à certaines classes de polymères possédant des monomères ayant des positions bloquées favorisant qu’une seule paire de liaisons C-H. Dans le cadre de ces travaux de doctorat, l’objectif général est d’étudier la polymérisation par PHAD afin d’accéder à des classes de monomères qui n’étaient pas envisageables auparavant et à étendre l’application de cet outil dans le domaine des polymères conjugués. Plus spécifiquement, nous avons étudié l’utilisation de groupements protecteurs et partants sur des unités de benzodithiophènes et de bithiophène-silylés. Suivant ces résultats, nos travaux ont porté sur la polymérisation de dérivés de bithiophènes avec des bromo(aryle)s, une classe de polymères fréquemment utilisée en électronique organique mais qui était jugée impossible à polymériser par PHAD auparavant. Cette étude a montré l’importance de contrôler la PHAD afin d’obtenir le polymère souhaité. Finalement, nous avons étudié l’effet du système catalytique sur le taux de β−ramifications lors de la synthèse de polymères à base de thiophènes. Dans cette dernière étude, nous avons démontré l’importance d’utiliser des outils de caractérisation adéquats afin de confirmer la qualité des polymères obtenus.Organic electronics is growing interest thanks to new possibilities it offers to facilitate the integration of electronic devices in our lives. With this new technology, we can consider novel products that are light, flexible, and inexpensive to produce. The three major classes of studied devices are organic photovoltaic cells (OPV) and organic field effect transistors (OFET).In recent years, particular attention has been paid to the method of preparation of the organic materials used in the fabrication of these devices. The polymerization by direct (hetero)arylation (DHAP) catalyzed by Pd is a powerful new tool that meets the needs of the area. DHAP provides a synthesis without organometallic derivative, which facilitates purification and reduces the number of steps and materials which makes possible the production at a lower cost. In addition, the PHAD allows the preparation of materials that were difficult or impossible to obtain before. However, the major drawback of the DHAP was its restriction to only certain classes of compounds. In this thesis, the project consists of studying the DHAP polymerization to open it to new classes of derivatives and expand its application in the field of organic electronics. First, the use of protecting groups and removable groups was studied on benzodithiophene and bithiophene-TMS units. Following these results, our work focused on the importance of controlling the polymerization when it is applied to the large polymer family of bromo(aryl)s with bithiophenes. This study has shown the importance of controlling the PHAD to obtain the desired polymer Finally, we studied the effect of the catalyst system to limit the β defects on polymers based of thiophene. We emphasis on the importance of using appropriate characterization tools to confirm the quality of the polymers obtained.
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Viana, Hugo Ricardo Matos. "Studies on the catalytic intramolecular arylation: application of continuous flow systems." Doctoral thesis, Universidade de Évora, 2015. http://hdl.handle.net/10174/18215.
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Currently, neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s disease (PD) represent an important worldwide health problem.
Over the last number of years, there have been many advances in the field of metal catalysed reactions. The palladium-catalysed intramolecular nucleophilic addition of arylborons and aryl halides to ketones constitutes an important methodology for the synthesis of chiral cycloalkanols.
Our main objective was the development of a new efficient protocol for accessing the 1-aminotetralin and 1-aminoindane skeletons (Chapters 3 and 4). A secondary goal was to obtain robust and reliable enantioselective versions of these reactions (Chapters 3 and 4). Numerous aldehyde substrates were synthesized and various cyclization reactions were carried out using these substrates (Chapter 3). We also compared the effectiveness of conducting these reactions under continuous flow conditions, with those carried out under batch conditions. Furthermore, some of our 3,3-dimethylchroman-4-ones and 3,3-dimethylchroman-4-ols were tested against AChE and BuChE enzymes. Chapters 1 and 2 contain literature reviews of this material.
We also report the attempted synthesis of a library of substituted 3-hydroxy-3-phenylbenzofuran-2(3H)-ones derived from a series of α-keto o-bromoaryl- and o-pinacolboranearyl ester substrates (Chapter 4). For the synthesis of the α-keto ester substrates, we looked at two different methodologies. Eight α-keto ester substrates were synthesized in very high or excellent yields. We also studied the cyclization reaction with 1-bromonaphthalen-2-yl 2-oxo-2-phenylacetate as our model substrate. Unfortunately, these attempts were unsuccessful and no cyclic product was obtained.
Additionally, we successfully developed a new methodology for the direct oxidative esterification of aldehydes (Chapter 5). Using this methodology, we synthesized nine new diether-esters in very good to excellent yields, which were subsequently tested for both AChE and BuChE inhibition. We also presented a strategy for the synthesis of interesting polyether macrocycles that includes the borylation of the synthesized diether-esters and a Suzuki-Miyaura coupling; Resumo:
Estudos sobre a arilação intramolecular catalítica – Aplicação de sistemas de fluxo contínuo
Atualmente, doenças neurodegenerativas como a doença de Alzheimer (DA) e a doença de Parkinson (DP) representam um problema importante de saúde em todo o mundo.
Ao longo dos últimos anos, tem havido muitos avanços no campo das reações catalisadas por metais. As reações de adição nucleofílica intramolecular catalisadas por paládio, de arilboronados e de haletos de arilo a cetonas, constituem uma metodologia importante para a síntese de ciclo-álcoois quirais.
O nosso objetivo principal foi o desenvolvimento de um novo protocolo eficiente para aceder a esqueletos de 1-aminotetralinas e 1-aminoindanos (capítulos 3 e 4). Um objetivo secundário era obter versões enantiosseletivas robustas e fiáveis dessas reações (capítulos 3 e 4). Numerosos aldeídos foram sintetizados e várias reações de ciclização foram realizadas utilizando estes substratos (capítulo 3). Também comparamos a eficácia da realização destas reações sob condições de fluxo contínuo com aquelas realizadas sob condições de “batch”. Algumas das nossas 3,3-dimetilcroman-4-onas e dos nossos 3,3-dimetilcroman-4-ols foram testados contra a AChE e BuChE. Os capítulos 1 e 2 contêm alguma literatura sobre este material.
Também relatamos a tentativa de síntese de uma biblioteca de 3-hidroxi-3-fenilbenzofuran-2(3H)-onas substituídas, derivadas de uma série de α-ceto ésteres e de ésteres de o-bromoaril- e o-pinacolboranaril (capítulo 4). Para a síntese de α-ceto ésteres, testamos duas metodologias diferentes. Oito α-ceto ésteres foram sintetizados com rendimentos muito elevados ou excelentes. Também estudamos a reação de ciclização usando 1-bromonaftalen-2-il-2-oxo-2-fenilacetato como substrato modelo. Infelizmente não obtivemos nenhum produto cíclico.
Adicionalmente, desenvolvemos com sucesso uma nova metodologia para a esterificação oxidativa direta de aldeídos (capítulo 5). Usando esta metodologia, sintetizamos nove di-éter-ésteres novos com rendimentos muito bons a excelentes, que foram posteriormente testados para inibição da AChE e da BuChE. Também apresentamos uma estratégia para a síntese de macrociclos de poliéteres interessantes, que incluí a borilação dos di-éter-ésteres sintetizados e um acoplamento Suzuki-Miyaura.
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Ovadia, Benjamin. "Nouvelles réactions radicalaires multicomposants : carbo-arylation, carbo-oximation, carbo-alcénylation d'oléfines." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0451/document.
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L’objectif de ces travaux de thèse a consisté en le développement de nouveaux accepteurs sulfonylés pour l’élaboration de processus multicomposants radicalaires originaux. De nouvelles réactions de carbo-arylation, carbo-oximation et carbo-alcénylation d’oléfines ont ainsi été mises au point. Nous avons, dans un premier temps, étudié la faisabilité de nouvelles réactions de carbo-hétéroarylation basées sur deux modes d’activation des hétérocycles. Cette méthodologie s’est toutefois révélée être un réel défi en raison de la non-complémentarité des polarités du système, entrainant la formation de plusieurs réactions secondaires et des rendements assez faibles.Dans une seconde partie nous avons étudié le diastéréocontrôle lors de réactions de carbo-oximation d’allylsilanes et d’esters chiraux. Lors de ces processus, les produits de carbo-oximation sont obtenus avec de bons niveaux de diastéréocontrôle mais avec des rendements modestes en raison de l’encombrement stérique et de l’apparition de réactions secondaires. La configuration relative des diastéréoisomères majoritaires n’a pas encore pu être établie avec certitude, mais des modèles d’état de transition peuvent toutefois être proposés afin de prédire la stéréochimie la plus favorable.Dans le but de nous affranchir de l’utilisation d’une quantité stoechiométrique de diétain nous avons également développé de nouveaux accepteurs bi-fonctionnels capables d’agir à la fois comme accepteurs de radicaux nucléophiles et comme sources de radicaux électrophiles via l’α-scission du radical alkylsulfonyle généré. Nous avons mis au point une méthode de préparation de ces accepteurs extrêmement simple et efficace permettant l’accès à une large série de composés.Dans une dernière partie nous avons étendu les résultats obtenus lors des réactions de carbo-alcénylation en préparant de nouveaux accepteurs halogénés et sulfonylés très appauvris en électron par la présence de groupements électroattracteurs. Nous avons finalement réalisé un premier test concluant de carbo-alcénylation à partir d’un vinylsulfoxyde permettant d’envisager la réalisation de ces réactions en version énantiosélective à partir de vinylsulfoxydes énantioenrichisThis thesis consists in the development of new sulfonylated acceptors for the elaboration of original free-radical multicomponent processes. Thereby, we have developed new free-radical carbo-arylation, carbo-oximation and carbo-alkenylation processes onto olefins.We have first studied the feasibility of new free-radical carbo-heteroarylation based on two different way of activation. This process proved to be very challenging due to the mismatch polarity between the different components, leading to the formation of side reactions and therefore relatively poor yield.In a second part, we examined the diastereocontrol arising from carbo-oximation of chiral allylsilanes and allylic esters. Carbo-oximation products are obtained with high level of selectivity, albeit in modest yields, due to steric hindrance and the formation of side-products. The relative configuration of the major diastereoisomer could not be established, but transition state models may be proposed to predict the most favorable stereochemistry. In order to overcome the use of stoechiometric amount of tin, we have developed new bi-functional reagents which can act both as a trap for nucleophilic radicals as well as a source of electrophilic radical via α-scission of generated alkylsulfonyl radicals. We have developed a very simple and efficient method for the preparation of these acceptors allowing an access to a wide range of compounds.In the final part, we extended the results obtained in the carbo-alkenylation reactions by preparing new activated halogenated and sulfonylated acceptors containing electron-withdrawing groups. We finally carried out a successful test on a carbo-alkenylation reaction using a vinylsulfoxide, offering an entry toward the development of such reactions in an enantioselective series starting from enantioenriched vinylsulfoxides
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Sahoo, M. K. "Visible light mediated photoredox catalytic dehydrogenation and C-H arylation reactions." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2018. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/4557.
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Grenier, François. "Synthèse de polymères d'isoindigo utilisant de nouvelles méthodes évolutives de polymérisation par (hétéro)arylation directe." Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/69362.
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Les matériaux polymères conjugués offrent une combinaison avantageuse de propriétés mécaniques, électroniques et de mise en œuvre permettant de produire des composantes minces, ultra-flexibles et peu coûteuses. Au fil des avancées techniques, ces matériaux émergents ont démontré qu'ils avaient le potentiel de révolutionner plusieurs technologies, notamment pour la production d'énergie solaire, dans les transistors à effet de champs et pour la fabrication de diodes électroluminescentes organiques. La composition entièrement organique de ces matériaux les rend modulables, car il est possible d'ajuster leurs propriétés en modifiant leur structure chimique. Ce faisant, les performances en dispositifs des polymères conjuguées se sont constamment améliorées au fur et à mesure que de nouveaux matériaux ont été synthétisés. En contrepartie, la complexité synthétique des matériaux a continuellement augmenté afin d'atteindre les performances requises. Pour rendre les polymères conjugués compétitifs avec les technologies existantes, il est crucial de les obtenir de façon simple et peu coûteuse. Au cours de ces travaux de doctorat, nous nous sommes concentrés à utiliser une approche combinée où de nouveaux matériaux à faible complexité synthétique sont produits par polymérisation par (hétéro)arylation directe (PHAD). Nos efforts se sont consacrés principalement à l'unité isoindigo, un monomère simple à synthétiser dont les performances en piles solaires et transistors organiques étaient prometteuses. Au cours des travaux, nous avons synthétisé plusieurs polymères de type p et de type n, mais les performances en dispositifs n'ont pas atteint le niveau désiré. En contrepartie, ces matériaux ont représenté un système idéal pour l'étude de la PHAD elle-même, en particulier son adaptation pour une utilisation à plus grande échelle. Contrairement aux polymérisations classiques de Suzuki, Stille, Kumada, etc., la PHAD permet la formation de liens C-C entre deux dérivés aromatiques par l'activation des liens C-H. Ces travaux ont démontré pour la première fois son application dans un réacteur en flux continu, ce qui permit d'améliorer la constance des lots et de simplifier la mise à l'échelle industrielle. Ensuite, nous avons développé des conditions réactionnelles robustes biphasiques ne nécessitant pas de pression élevée. Ces conditions réactionnelles évolutives ont pu être appliquées avec succès à d'autres polymères et ont permis d'obtenir des matériaux contenant exceptionnellement peu de défauts et ayant des masses molaires élevées. Ces résultats démontrent le potentiel de la PHAD pour la synthèse de polymères conjugués de façon plus simple et éco-responsable que les méthodes précédemment proposées.Conjugated polymers offer an advantageous combination of mechanical, electronical and processing properties that allow the production of thin, ultra-flexible and inexpensive electronic components. Along with technical advances, these emerging materials demonstrated that they had the potential to revolutionize several technologies, notably solar energy production, field-effect transistors and for the fabrication of organic light-emitting diodes. The entirely organic composition of these materials makes it possible to modulate their properties by modifying their chemical structure. Consequently, the performances of conjugated polymers in devices constantly improved along with the synthesis of new materials. In return, the synthetic complexity of the materials continuously increased to achieve the required performances. To make conjugated polymers competitive with existing technologies, it is crucial to obtain them in a simple and inexpensive manner. During these Doctorate studies, we focused on using a combined approach where new materials with reduced synthetic complexity were produced using direct (hetero)arylation (DHAP). Our efforts were devoted mainly to the isoindigo unit, a monomer that is simple to synthesize and that is promising for use in organic solar cells and transistors. Over the course of this work, we synthesized several p-type and n-type polymers, but their performances in devices did not reach the expected numbers. However, these materials were an ideal system to study DHAP itself, and specifically for its adaptation to use at larger scales. Contrary to classical polymerization, such as Suzuki, Stille, Kumada, etc., DHAP allows the formation of C-C bonds between two aromatic derivatives by activating C-H bonds directly. This work demonstrated for the first time its application in a continuous flow reactor, which allowed an improvement in batch-to-batch variations and simplified its application in industrial scale. We then developed robust biphasic reaction conditions that do not require high pressure. These scalable reaction conditions were successfully applied to other polymers and allowed us to obtain materials containing exceptionally few defects v along with high molecular weights. These results demonstrate the potential of DHAP to synthesize conjugated polymers in a simpler and eco-friendlier way than previously proposed methods.