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1
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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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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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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Fujino, Daishi. "Studies on Palladium-Catalyzed Arylative Cyclization Reactions." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188508.
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Ljungkvist, Oskar. "Mechanochemistry : C-H arylation and annulative π-extension reactions attempted inball mill." Thesis, Uppsala universitet, Institutionen för kemi - BMC, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382088.
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Sambiagio, Carlo. "Investigations on the use of amidic ligands in copper-catalysed arylation reactions." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/10153/.
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This thesis reports investigations on the use of amidic ligands, in particular picolinamide ligands, in copper-catalysed arylation of nucleophiles with aryl halides. An introduction to the field of copper-catalysed arylations of nucleophiles, mostly focusing on the mechanistic aspects of these processes, from the early investigations to the most recent developments, is reported in Chapter 1. Following this introduction, the results of this research are presented in three chapters, each dealing with a different topic. Chapter 2 reports on the synthesis of a range of differently substituted picolinamide ligands and their use in the copper-catalysed arylation of phenols and amides. The catalytic screenings reported in this chapter are the basis for the mechanistic investigations reported in Chapter 4. A range of phenols, amides and aryl halides were tested under optimised conditions to assess the validity of the method. All the coupling products were isolated and characterised. Chapter 3 describes the synthesis of copper complexes with picolinamide ligands, to be used for mechanistic investigations. Five different types of complexes, with differently substituted ligands, were obtained, and their structural features in the solid state are summarised in this chapter. Discussion on the mechanism of formation of these complexes, and on the role of the base in the process is also included. Investigations on the mechanism of the coupling reaction between phenols and aryl halides, facilitated by picolinamide ligands, are reported in Chapter 4. The complexes synthesised in Chapter 3, used as pre-catalysts for the coupling process, and electrochemical measurements on these complexes, are employed to investigate the role of the electronic properties of the ligands in the reaction, and its influence on the metal centre. Other miscellaneous experiments, such as radical clock experiments, are also reported. The final two chapters of this thesis, Chapters 5 and 6, contain general conclusions and suggestions for further investigation topics (Chapter 5), and detailed experimental procedures and characterisation data for all of the compounds prepared in Chapters 2-4 (Chapter 6).
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Tanji, Yutaka. "Steric Effect of Carboxylate Ligands on Pd-Catalyzed C-H Bond Arylation Reactions." Kyoto University, 2020. http://hdl.handle.net/2433/253293.
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Sundalam, Sunil Kumar. "The Discovery and Development of Metal-Free Arylation Reactions with Unsymmetrical Diaryliodonium Salts." PDXScholar, 2017. https://pdxscholar.library.pdx.edu/open_access_etds/3764.
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Functionalizing arenes and heteroarenes has been an active area of research since the 19th century, due to the presence of these molecular structures in many industrially important sectors. A tremendous amount of research has been published in achieving these chemical transformations using stoichiometric reagents and transition metal-catalyzed reactions. However, challenges still remain. An alternative and comparable methodology to metal-catalyzed reactions to overcome the drawbacks will advance this particular area of research is desirable.
Hypervalent iodine compounds offer a promising approach to metal-free arylation reactions. These mild, air and moisture stable compounds have showed significant success as non-toxic and metal-free reagents for the arylation reactions. In particular, unsymmetrical diaryliodonium salts offer functionalization of complex arene structure in an efficient and sustainable pathway.
A base-mediated coupling reaction for the metal-free synthesis of alkyl-aryl ethers by using unsymmetrical diaryliodonium salts and aliphatic alcohols is described. This method shows broad substrate scope with respect to both of the coupling partners to produce industrially useful alkyl-aryl ethers in moderate to excellent yields. The reaction is operationally simple, proceeds at mild temperature, and is atom-economical. Sustainability and synthetic utility of this reaction is demonstrated by the use of unsymmetrical aryl(mesityl)iodonium salts as the arylating agents. A limitation of poor reactivity of electron rich unsymmetrical diaryliodonium salts was overcome by designing 2nd generation conditions and using trimethoxy benzene (TMP) as the auxiliary group.
Additionally discovery and development of an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts is presented. The aryne intermediates are generated by ortho C-H deprotonation of aryl(mesityl)iodonium salt with an amide base and subsequently trapped in a cycloaddition reaction with furan in moderate to good yields. Selective iodonium moiety elimination is discussed and the effect of auxiliary and temperature to reduce the regioisomeric ratio is demonstrated. Finally, additional coupling partner including benzyl azide and aliphatic amines are presented to show further utility of this methodology. Also, mechanistic investigations leading to the moderate reactivity of some electron rich unsymmetrical diaryliodonium salts is discussed.
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Schroll, Peter [Verfasser], and Burkhard [Akademischer Betreuer] König. "Photocatalytic single-electron transfer reactions: the Photo-Meerwein arylation / Peter Schroll. Betreuer: Burkhard König." Regensburg : Universitätsbibliothek Regensburg, 2016. http://d-nb.info/1096750597/34.
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Cooke, Michael Liam. "Development of novel arylation and alkenylation reactions using hypervalent iodine reagents and copper catalysis." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609862.
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Aoki, Yuma. "Development of Iron-Catalyzed C-N and C-C Bond Forming Reactions toward Functional Arylamine Synthesis." Kyoto University, 2019. http://hdl.handle.net/2433/242518.
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Pérez, Janer Ferran. "Palladium in azaheterocyclic synthesis: α-arylation of sulfones, domino processes and C-H carbene insertion reactions." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/586010.
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Among transition metals used in organic chemistry, palladium has greatly contributed to the development of modern organic synthesis. This thesis is focused on the development of novel and efficient methodologies for the synthesis of nitrogen heterocycles employing palladium catalysed reactions. In this work, DFT calculations complement the experimental work in order to gather mechanistic insights of the reported transformations.
In the first part of the thesis an exhaustive study of the intramolecular palladium catalysed α-arylation of sulfones is described. This metal-mediated process was successfully combined with conjugated additions to generate domino processes of two, three and four steps that allowed the synthesis of functionalised indoles and tetrahydroisoquinolines.
From a mechanistic point of view, DFT calculations suggest that a concertated metalation-deprotonation process followed by reductive elimination is involved in the indole ring formation.
Next, the intramolecular palladium catalysed α-arylation reaction was explored using nucleophiles derived from sulfonates, sulfonamides and phosphonates. Although feasible, these nucleophiles are less efficient in the intramolecular cyclization leading to the tetrahydroisoquinoline ring. Domino processes based on α-arylation/Michael addition reactions starting from sulfonates and sulfonamides using diverse Michael acceptors were also reported. Attempts to pursue domino process starting from phosphonates were unsuccessful.
In the second part of the thesis, a synthetic methodology for the synthesis of nitrogen heterocycles based on palladium catalysed decomposition of α- diazoacetamidas was studied.
Decomposition of α-diazo-α-(methoxycarbonyl) acetanilides catalyzed by palladium leads to the chemoselective Csp2-H insertion and the synthesis of oxindole type products. Although Pd(0) and Pd(II) catalysts are able to promote this transformation, Pd(0) catalysts such as Pd2(dba)3 or [IMes)Pd(NQ)]2 yield the best results.
DFT calculations suggest that the insertion reaction involves a novel stepwise
mechanism that implies a palladium mediated 1,5-hidrogen migration followed by reductive elimination that yields two products: the insertion product and the Pd(0) catalyst.
Finally, we studied the palladium catalysed decomposition of α-diazo-α- (methoxycarbonyl) acetamides to promote intramolecular Csp3-H insertion to form β-lactams. In these transformations, though both Pd (0) and Pd(II) catalysts can be used, Pd(II) complexes were found to be the most versatile and efficient.De entre todos los metales de transición utilizados en síntesis orgánica, el paladio ha ocupado un lugar central durante décadas y ha sido uno de los metales que más ha contribuido al desarrollo de este campo. En la presente Tesis Doctoral se han desarrollado diversas metodologías para la síntesis de heterociclos nitrogenados basados en procesos dominó catalizados por paladio. Por otro lado, los estudios experimentales se han combinado con estudios computacionales DFT para desentrañar el mecanismo implicado en estas transformaciones. En la primera parte de la Tesis Doctoral se ha llevado a cabo un extenso estudio de la reacción de α-arilación intramolecular de sulfonas catalizado por paladio. La combinación de la reacción de α-arilación con la subsiguiente adición conjugada a diversos aceptores de Michael, ha permitido el desarrollo de procesos dominó en 2, 3 y 4 etapas para la síntesis de tetrahidroisoquinolinas e indoles diversamente funcionalizados. Los estudios computacionales DFT de este proceso para la formación de indoles sugieren que la reacción de α-arilación transcurre mediante un proceso de desprotonación-metalación concertado (CMD) seguido de una eliminación reductora. H SO2R' SO2R' Pd(0) I base SO2R' SO2R' PhO2S SO2R' n= 0,1 N n Aza-Michael N -arilación N n n adición N R conjugada n=1 SO2R' SO2R' adición conjugada n=0 R'O2S SO2R' N -eliminación N R R A continuación, la reacción de α-arilación intramolecular catalizada por paladio se ha extendido a la utilización de sulfonatos, sulfonamidas y fosfonatos. Aunque los tres tipos de nucleófilos pueden utilizarse en la reacción de α-arilación para la preparación de tetrahidroisoquinolinas, la reacción transcurre de manera menos eficiente en relación a las sulfonas estudiadas. Asimismo, la versatilidad de los procesos dominó desarrollados a partir de ésteres sulfónicos y sulfonamidas fue menor. Por otro lado, los fosfonatos han resultado ser completamente inactivos en los diferentes procesos domino estudiados. La reacción de α-arilación de sulfonatos, sulfonamidas y ésteres sulfónicos también se ha estudiado computacionalmente. Estos estudios han puesto de manifiesto que la reacción transcurre por mecanismos distintos en función del nucleófilo y de la base utilizada. En la segunda parte de la Tesis, se ha estudiado la viabilidad de los complejos de paladio en reacciones de inserción de carbenos en enlaces C-H generados a partir de α-diazoacetamidas. La descomposición de las α-diazo-α-(metoxicarbonil) acetanilidas catalizadas por complejos de paladio ha dado lugar a la formación de oxindoles como resultado de una inserción quimioselectiva en el enlace Csp2-H. Aunque tanto los catalizadores de Pd(0) como los de Pd(II) pueden promover esta reacción de inserción, los mejores resultados se han obtenido al utilizar complejos de Pd(0), en especial Pd2(dba)3 o [(IMes)Pd(NQ)]2. Los cálculos computacionales DFT de este proceso sugieren que la inserción tiene lugar mediante un mecanismo por etapas inédito que implica una migración 1,5 de hidrógeno promovida por el paladio seguido de un proceso de eliminación reductora. Finalmente, también se ha estudiado la descomposición de α-diazo-α- (metoxicarbonil) acetamidas catalizada por paladio para promover inserciones Csp3-H y la formación de β-lactamas. Aunque tanto los catalizadores de Pd(0) como de Pd(II) son capaces de promover esta reacción, los catalizadores de Pd(II) son más eficientes y versátiles.
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Phipps, Robert James. "Copper catalysis as a tool for developing novel and selective arylation reactions using hypervalent iodine reagents." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608863.
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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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Tomohara, Keisuke. "New aspects in chemistry of axially chiral enolates: Developments of asymmetric reactions via C-O axially chiral enolates and α-arylation of amino acids derivatives." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157896.
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Bassoude, Ibtissam. "Synthèse de nouveaux dérivés pyrazolo[1,5-a]pyrimidiniques à visée biologique." Phd thesis, Université d'Orléans, 2012. http://tel.archives-ouvertes.fr/tel-00789954.
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Nos travaux de thèse portent sur la mise au point de nouvelles méthodes de synthèse permettant l'accès de façon rapide et efficace à différents dérivés pyrazolo[1,5-a]pyrimidiniques diversement fonctionnalisés.La première partie de ce travail concerne l'étude et l'application de la condensation de la pyran-2-one avec les 5(3)-amino-3(5)-arylpyrazoles que ce soit par chauffage classique ou sous irradiation micro-onde. Par la suite, un nouveau procédé d'(hétéro)arylation pallado-catalysé direct régiosélectif a été mis à profit pour élaborer des pyrazolo[1,5-a]pyrimidines fonctionnalisées tant en position 3 que sur le méthyle situé sur le sommet 7 de la 5,7-diméthylpyrazolo[1,5-a]pyrimidine.Le dernier volet de ce mémoire a été consacré à la préparation des entités pyrazolo[1,5-a]pyrimidiniques substituées en position 7 par des motifs benzyliques et ce, via une procédure " one-pot ", sous irradiation micro-onde, constituée d'une réaction d'arylation directe pallado-catalysée suivie d'une saponification-décarboxylation.
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Naas, Mohammed. "Synthèse et fonctionnalisation de nouveaux dérivés d’indazoles à visée thérapeutique." Thesis, Orléans, 2016. http://www.theses.fr/2016ORLE2009/document.
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L’accès à de nouveaux composés hétérocycliques originaux biologiquement actifs nécessite la mise au point de nouvelles méthodes de synthèse rapides et efficaces. Dans ce contexte, nous nous sommes intéressés à la réactivité des indazoles. Dans la première partie, nous avons étudié la sélectivité des couplages de type Suzuki, pour fonctionnaliser la position 3 d’indazoles possédant la fonction NH libre. Par la suite, un nouveau procédé d’(hétéro)arylation direct pallado-catalysé régiosélectif a été mis à profit pour synthétiser des indazoles fonctionnalisés tant sur la position 3 que sur le sommet 7. Nous avons ensuite montré la possibilité d’accéder à des entités disubstituées indazoliques en une seule étape, via une procédure "one-pot". Afin d’accroître la diversité autour du noyau indazole, nous avons mis au point une réaction d’alcénylation oxydative pallado-catalysée, des (2H)- et (1H)-indazoles sur les sommets C-3 et C-7. Pour exemplifier cette méthodologie, nous avons développé une synthèse en trois étapes du Gamendazole, composé actuellement en phase clinique pour la contraception masculine et ce, en utilisant l’alcénylation directe en C3 d’(1H)-indazoles convenablement fonctionnalisés. Le dernier volet de ce mémoire a été consacré à la préparation de composés à structure indazolique contenant une fonction sulfonamide afin de générer des librairies de dérivés substitués par un tel motif, dans le but de les tester biologiquement dans le domaine des anticancéreuxAccess to new biologically active compounds requires the development of new rapid and efficient methods for the synthesis of original heterocyclic scaffolds. In this context, we decided to focus particularly on the reactivity of indazoles. First, we studied the selectivity of Suzuki cross-coupling reaction to functionalize position 3 of the indazole with the free NH function. Indeed, we have described the first example of the direct and regioselective palladium-catalyzed (hetero)arylation of indazoles, the reaction may be induced to occur at either in position 3 and 7. We then showed the possibility of "one-pot" synthesis of disubstituted indazolic entities. Moreover, in order to increase diversity around the indazole scaffold, we developed a direct and regioselective alkenylation of (2H)- and (1H)-indazoles by oxidative palladium catalyzed at the C-3 and C-7, then we envisaged a three staps synthesis of Gamendazole, molecule currently in clinical phase for male contraception, by using the direct alkenylation at C3 of the suitably functionalized (1H)-indazoles. The last part of this report was dedicated to the preparation of indazoles containing a sulphonamide function, with the aim of biological testing them as potentially anti-cancer candidates
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Naturale, Guillaume. "Approches radicalaires pour la fonctionnalisation directe de quinones à visée anticancereuse." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14635/document.
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Dans le cadre d’un programme de recherche dédié à la découverte de petites molécules à visée anticancéreuse, nous avons envisagé de concevoir des composés originaux dérivés de quinones. Notre premier objectif a été d’élaborer des mimes non-peptidiques de la protéine Smac, susceptibles de participer à relancer le phénomène d’apoptose, dont la structure est rigidifiée par des contraintes conformationnelles. Par ailleurs, les kinases et les phosphatases, jouant des rôles complémentaires de phosphorylation / déphosphorylation dans le cadre du contrôle du cycle cellulaire notamment, apparaissent aussi comme des cibles intéressantes. Une étude attentive de leurs inhibiteurs connus nous a permis de mettre en avant des analogies structurales qui nous ont conduit à vouloir synthétiser des motifs fonctionnalisés de dérivés de naphtoquinones.L’introduction directe de chaînes latérales aliphatiques sur nos substrats, par création de liaisons de type C(sp2)–C(sp3), a été rendue possible grâce au développement d’une méthodologie de décarboxylation radicalaire. Dans les conditions réactionnelles mises au point, le couple Ag(I)/S2O82- est utilisé comme initiateur radicalaire et autorise la génération de radicaux alkyles par décarboxylation d’acides aminés. L’introduction directe de cycles aromatiques fonctionnalisés, via la création de liaisons de type C(sp2)–C(sp2), a été réalisée par l’intermédiaire de la génération de radicaux aryles issus de sels de diazonium stables ou d’anilines. Les procédés décrits dans ce manuscrit nous ont permis d’apporter certains éclaircissements sur la réactivité des substrats et sur les mécanismes réactionnels impliquésIn our ongoing course dedicated to the discovery of small anticancer molecules, we designed novel quinone derivatives. Our first objective was to fashion non-peptidic Smac mimics, able to trigger apoptosis in tumor cells, displaying a structure rigidified by conformational restrictions. Otherwise, the kinases and the phosphatases, acting as phosphorylating / dephosphorylating agents mostly in the control of the cell cycle, were thought to be other relevant biological targets. An intent study of their known inhibitors allowed us to underline trends in their chemical structure and made us plan the synthesis of functionalized naphthoquinones.A dedicated approach involving radical decarboxylation of amino acids allowed the introduction of aliphatic side chains on our substrates though C(sp2)–C(sp3) bond formation. Ag(I)/S2O82- was used as alkyl radical initiator and the direct C-H alkylation of the quinonic positions could take place. C(sp2)–C(sp2) bonds were created through aryl radicals generation from stable diazonium salts or anilines which allowed the direct C-H arylation of quinones. The procedures described along this manuscript let us formulate several advances on the substrates reactivity and on the reaction mechanisms involved
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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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Zine, Khalid. "Synthèse régio- et stéréosélective du 4,4,4-trifluorobut-2-énoate d'éthyle porteur d'un groupement tributylstannyl en position alpha ou bêta : réactivité cupro-catalysée des vinylétains en l'absence de complexes du palladium." Thesis, Tours, 2011. http://www.theses.fr/2011TOUR4044/document.
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Vu l’importance des molécules fluorées dans différents domaines et vu la réactivité engendrée par le 4,4,4-trifluorobut-2-ynoate d’éthyle 1 lors des travaux antérieurs réalisés au laboratoire, nous avons décidé d’étudier le comportement de dérivé fluoré 1 vis-à-vis d’hydrure tributylétain sans l’emploi de catalyseurs ou d’additifs. Le but est d’accéder à de nouveaux synthons fluorés par voies originales.Après une étude préliminaire pour effectuer cette réaction d’hydrostannation dans les meilleures conditions, nous avons réalisé pour la première fois la synthèse totalement régio- et stéréosélective des vinylétains (Z)-2α et (Z)-2β par un simple choix de solvant et sans l’utilisation d’aucun additif. Ces résultats inédits et très encourageants, nous ont conduis à étendre cette stratégie à d’autres hydrures comme l’hydrure de diphénylphosphine et l’hydrure de triphénylgermane..Les vinylétains (Z)-2α et (Z)-2β- de configurations bien définies sont des réactifs de choix pour élaborer de nouvelles structures fonctionnelles trifluorométhylées. En effet, le couplage cupro-catalysé de ces vinylétains en présence d’une quantité catalytique de CuI (10 moles%) avec une variété de bromures d’allyles, de propargyles, d’aryles, de benzyles et d’alcynyles conduisent à une grande variété de composés fluorés jamais décrits dans la littérature.Les méthodes de synthèse développées dans ce travail sont originales et permettent la synthèse d’une grande famille de composés fluorés avec un moindre coûtThe development of a simple method to obtain perfluoroalkylated building blocks for their subsequent utilization in the synthesis of Rf-containing compounds is therefore essential to organofluorine chemistry. Perfluoroalkylated vinyl metals constitute an important class of these building blocks.In order to prepare a new perfluoroalkylated bulding blocks, we investigated transition metal-catalyzed-free hydrostannylation of ethyl 4,4,4-trifluorobut-2-ynoate 1. The hydrostannylation took place smoothly in the absence of additive, providing regioselectively high yields of the corresponding α or β stannylated alkenoates depending on the nature of the solvent used. Indeed, we have demonstrated that the hydrostannylation of 1 in hexane provided the β-stannylated product with high regioselectivity (>95%) and excellent yield (>97%). Using methanol as solvent, total α-regioselectivity of the hydrostannylation of 1 was observed, providing α -tributylstannylacrylate as the sole regioisomer in a nearly quantitative yield.Theses new vinyltins reagents readily undergo copper (I) catalyst coupling reactions with various electrophiles as allyl, propargyl, benzyl and alkynyl bromides to provide good yields of the new corresponding acrylates esters bearing a β-trifluoromethyl group.This method provided a new efficient entry to this important class of compounds
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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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Grosse, Sandrine. "Imidazo[1, 2-b]pyrazoles, imidazo[1, 2-a]imidazoles : synthèse, fonctionnalisation et évaluation biologique." Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2056.
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Les imidazo[1,2-b]pyrazoles tout comme les imidazo[1,2-a]imidazoles sont des entités présentant diverses applications intéressantes notamment dans le domaine pharmacologique. Cependant, malgré ce potentiel, ces structures hétérobicycliques ont été, jusqu’à ce jour, relativement peu étudiées tant au niveau de leur préparation que de leur fonctionnalisation. De ce fait, ces travaux de thèse ont pour objet la mise au point de nouvelles voies d’accès à ces systèmes bicycliques et ce, au départ de substrats facilement accessibles. Des stratégies de fonctionnalisation de ces charpentes moléculaires ont ensuite été développées dans le but de concevoir des librairies diversifiées de ce type de composés, librairies destinées à être évaluées biologiquement. Les premiers résultats d’évaluation sur des lignées cancéreuses de dérivés imidazo[1,2-b]pyrazoliques sont également présentésImidazo[1,2-b]pyrazoles and imidazo[1,2-a]imidazoles are entities with some interesting applications in pharmacology. However, despite this potential, few methods of preparation and direct functionalisation of the heterocyclic moiety have been described. In this context, the overall goal of our research is to develop new routes to these bicyclic systems from readily available starting materials. Strategies of functionalisation of the heterocyclic moiety were then explored in order to design diversified libraries for the evaluation of potential biological activities. Herein, the results of the tests of imidazo[1,2-b]pyrazole series against various cancer lines are reported
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Seo, Sangwon. "Decarboxylative and direct functionalisations of aromatic compounds." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/decarboxylative-and-direct-functionalisations-of-aromatic-compounds(a9ddab1b-86a0-491e-a95b-d6b40c8bd7ab).html.
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Aromatic rings are privileged structures found in a diverse range of natural and synthetic compounds, thus synthetic methods for their functionalisations are important in organic synthesis. Despite significant advancements made, especially in the field of transition metal catalysis, work still continues for the development of milder, more efficient, and more atom economical reactions. We describe here our efforts towards the development of decarboxylative/direct C(aryl)–N and C(aryl)–C bond forming reactions using aromatic carboxylic acids and unfunctionalised arenes as cheap and widely available aromatic sources. The investigations into copper-catalysed and copper/palladium-catalysed intermolecular and copper/silver/palladium-catalysed intramolecular decarboxylative amination of aromatic carboxylic acids are reported. A new approach to decarboxylation of benzoic acids is also described. The reaction uses silver (I) catalyst and peroxydisulfate salt to generate aryl radicals via oxidative decarboxylation. The applications of this approach in intra- and intermolecular decarboxylative C–H arylation, and protodecarboxylation are described. Also described is the development of silver-catalysed trifluoromethylation of simple arenes and heteroarenes. The reaction proceeds via radical trifluoromethylation using trimethyl(trifluoromethyl)silane as the trifluoromethyl radical source. This method has been applied to the trifluoromethylation of complex agrochemical molecules, proving its synthetic utility in late-stage functionalisation. Furthermore, we describe the exploitation of trifluoroacetate derivatives as cheap trifluoromethylating reagents in copper-mediated decarboxylative C–H trifluoromethylation of 2-phenylpyridine.
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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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Felipe-Blanco, Diego. "Salicylic Acid-Catalyzed Radical Arylations from In-situ Formed Arenediazonium Salts." Doctoral thesis, Universidad de Alicante, 2020. http://hdl.handle.net/10045/112757.
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In this thesis, it has been studied the deamination of aromatic amines, through in situ formed diazonium salts as reaction intermediates, catalyzed by salicylic acid, a nontoxic, eco-friendly and economic catalyst. In the early part of the thesis (Chapter I) it has studied the deamination process using THF as solvent as hydrogen donor and anilines as radical source, to carry the hydrodeamination reaction, as well as the process in its deuterodeamination manner using deuterated solvent. Following with this study in Chapter II and Chapter III, it has been studied the addition of the aromatic radicals, generated with the methodology employed in the first chapter, to different types of double bond, to form α-arylketones (Chapter II) and γ-aryl lactones, throw a following intramolecular cyclization (Chapter III). Finally, in Chapter IV was studied the construction of arylphosphonates, starting from anilines as radical source, and triphenylphosphite, and in this case specially, mechanism was hard explored. In every work, the methodologies could be scaled-up above 1 g, reaction mechanisms were proposed and studied through control and mechanistical experiments, and follow reactions were carried out.
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Gonçalves, Renato Sonchini [UNESP]. "Síntese e caracterização de amino ácidos e ésteres n-(aminoalquil)-lactâmicos derivados do paba com potencial atividade biológica." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/99656.
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Amino ésteres lactâmicos derivados do PABA e que podem ser potencialmente bioativos, por exemplo, como anestésicos locais, foram sintetizados com bons rendimentos por uma reação seletiva de SnAr de ácidos benzóicos com n-(3-aminopropil)-lactamas seguida por esterificação com aminoálcoois terciários. Produtos da N-arilação do N, N-dimetilformamida foram também obtidos através da esterificação direta do ácido 4-cloro-3-nitrobenzóico
Lactamic amino esters PABA-related, and can potentially bioactive, for exemple, as local anesthetics were synthesized in good yields by a selective 'S IND. n'Ar reactions of benzoic acids with N-(3-aminopropyl)lactams followed by esteterification with tertiary aminoalcohols. Products of the N-arylation with N,N-dimethylformamide are also obtained through of direct esterification of 4-chloro3-nitrobenzoic acid
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Gonçalves, Renato Sonchini. "Síntese e caracterização de amino ácidos e ésteres n-(aminoalquil)-lactâmicos derivados do paba com potencial atividade biológica /." Bauru : [s.n.], 2010. http://hdl.handle.net/11449/99656.
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Orientador: Eduardo René Pérez GonzálesBanca: Alvicler Magalhães
Banca: Wanda Pereira Almeida
O Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, PosMat, tem caráter institucional e integra as atividades de pesquisa em materiais de diversos campi da Unesp
Resumo: Amino ésteres lactâmicos derivados do PABA e que podem ser potencialmente bioativos, por exemplo, como anestésicos locais, foram sintetizados com bons rendimentos por uma reação seletiva de SnAr de ácidos benzóicos com n-(3-aminopropil)-lactamas seguida por esterificação com aminoálcoois terciários. Produtos da N-arilação do N, N-dimetilformamida foram também obtidos através da esterificação direta do ácido 4-cloro-3-nitrobenzóico
Abstract: Lactamic amino esters PABA-related, and can potentially bioactive, for exemple, as local anesthetics were synthesized in good yields by a selective 'S IND. n'Ar reactions of benzoic acids with N-(3-aminopropyl)lactams followed by esteterification with tertiary aminoalcohols. Products of the N-arylation with N,N-dimethylformamide are also obtained through of direct esterification of 4-chloro3-nitrobenzoic acid
Mestre
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Dell'Acqua, M. "NEW SYNTHETIC STRATEGIES FOR THE PREPARATION OF HETEROCYCLIC AND HETEROPOLYCYCLIC COMPOUNDS." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/170500.
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The aim of the project of this doctoral thesis is the development of new synthetic strategies for the preparation of heterocyclic and heteropolycyclic compounds of potential interest in biological and pharmacological fields. In particular, we studied new general, flexible and regioselective synthetic approaches to oxygen and nitrogen heterocycles. We showed the versatility of nucleophilic addition/annulation domino reactions of alkyne compounds bearing a proximate nucleophile in the synthesis of heterocyclic systems, such as dihydroisobenzofurans, isoquinolines and naphthyridines. These approaches have been successfully transformed in Pd-catalysed multicomponent processes involving a one-pot coupling/addition/cyclisation sequence starting from the simple building blocks, such as ortho-bromoarylaldehydes, terminal alkynes and methanol or ammonia. In some cases, the reactivity of less reactive alkyne substrates has been enhanced by the catalysis of alkynophilic transition metals, such as gold and silver. In particular, we reported a new silver-catalysed approach to 2-methylisoquinolines and 5-methyl-1,6-naphtyridines by tandem addition/cyclisation of γ-ketoalkynes with ammonia. The domino approach has been also extended to 2-acetyl-N-propargylpyrroles for the synthesis of pyrrolo[1,2-a]pyrazine. In this case TiCl4 revealed to be the best promoter. Microwave heating demonstrated to be able to improve the efficiency of both domino and multicomponent processes. Finally, the project developed at the Institut für Organische und Biomolekulare Chemie in the Georg-August-Universität Göttingen (Germany), under the supervision of Prof. L. Ackermann, concerned with the direct arylations of indoles and pyrroles with differently substituted diaryliodonium salts in the absence of metal catalysts. The protocol proved broadly applicable, thereby enabling C-H bond functionalisations of free (NH)- as well as N-substituted indoles and pyrroles.
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Benhaddou, Rachida. "Arylation de doubles liaisons catalyses par le palladium : influence de differents facteurs sur la cinetique de la reaction, etude de nouvelles syntheses d'aryl-c-glycosides." Paris 6, 1988. http://www.theses.fr/1988PA066065.
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Zhang, Yin. "Backbone decoration of imidazol-2-ylidene ligands with amino groups and their application in palladium catalyzed arylative amination reaction." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30109/document.
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Ce travail s'inscrit dans le cadre de la chimie des carbènes N-hétérocycliques (NHC) et s'articule autour de la fonctionnalisation directe de l'hétérocycle des l'imidazol-2-ylidènes par substitution formelle d'un ou deux groupements diméthylamino. Deux nouvelles catégories de NHCs ont d'abord été obtenues par cette stratégie, dénommées 4-(diméthylamino)imidazol-2-ylidène IArNMe2 et 4,5-bis(diméthylamino)imidazol-2-ylidène IAr(NMe2)2. Les sels d'imidazolium précurseurs de ces NHCs, à savoir le triflate de 4-(diméthylamino)imidazolium (IArNMe2)·HOTf et le triflate de 4,5-bis(diméthylamino)imidazolium (IAr(NMe2)2)·HOTf, ont été synthétisés en couplant la formamidine disubstituée correspondante avec le N,N-diméthyl-chloroacétamide et le 1,2-dichloro-1,2-bis(diméthylamino)éthylène généré in situ respectivement. La quantification des propriétés électroniques des deux nouveaux NHCs a été réalisée à l'aide des complexes de type [Rh(IMes(NMe2)xCl(CO)2], montrant que la donation électronique des ligands NHCs augmente séquentiellement par la décoration avec un ou deux groupements diméthylamino, tandis que les propriétés de p-rétrodonation des NHCs ne sont que légèrement influencées. Par la suite, les complexes de palladium Pd-PEPPSI-IPrNMe2 et Pd-PEPPSI-IPr(NMe2)2 (PEPPSI : Pyridine Enhanced Preparation Purification Stabilization and Initiation) ont été préparés par des voies de complexation classiques. Les propriétés stériques des ligands a été évaluée par la mesure du pourcentage de volume occupé (%Vbur), et il est apparu que les propriétés stériques de ces deux nouveaux ligands NHCs sont également accrues. Les activités catalytiques des deux pré-catalyseurs ont été évaluées en amination de type Buchwald-Hartwig et comparées avec celle de la référence Pd-PEPPSI-IPr. Le pré-catalyseur Pd-PEPPSI-IPr(NMe2)2 s'est révélé le plus actif en amination des chlorures d'aryle à température ambiante. Il constitue également le catalyseur Pd-NHC le plus efficace et le plus général connu à ce jour en permettant de réaliser l'amination des chlorures d'aryle avec une charge de catalyseur très faible (jusqu'à 50 ppm), ou à l'aide d'une base faible telle que le carbonate de césium, et même d'activer les tosylates d'aryle, substrats beaucoup plus difficiles que les chlorures d'aryle . Afin de rationaliser au mieux les effets observés en catalyse en termes de propriétés stéréoélectroniques des ligands NHCs, le squelette arrière aminé des imidazol-2-ylidènes a été dérivatisé plus avant, soit en augmentant la contrainte stérique du groupe NMe2 dans IAr(NMe2) en ciblant le ligand IAr(NiPr2), soit en remplaçant formellement un des groupes amino par un groupe éléctro-attracteur tel un halogène dans le ligand IAr(NMe2)2. Alors que le sel d'imidazolium (IArNiPr2)·HOTf a été synthétisé suivant la même méthode que (IArNMe2)·HOTf, l'halogénation oxydante du squelette d'arrière de (IArNMe2)·HOTf par du NCS ou du NBS a donné les sels (IArNMe2, X)·HOTf avec de très bons rendements dans des conditions très douces. Il convient de noter que cette réactivité originale a été également observée sur les complexes de rhodium(I) et le palladium(II) du ligand IAr(NMe2). Les influences électroniques et catalytiques de ces modifications ont été étudiées de la même façonThis work is incorporated within the framework of the chemistry of N-Heterocyclic Carbenes (NHCs) and aims at functionalizing the skeleton of imidazol-2-ylidenes by attachment of one or two amino groups. Two new NHC classes were first obtained by this strategy, namely the 4-(dimethylamino)imidazol-2-ylidene IArNMe2 and the 4,5-bis(dimethylamino)imidazol-2-ylidene IAr(NMe2)2. The synthesis of the precursors of these NHCs, the 4-(dimethylamino)imidazolium triflates (IArNMe2)·HOTf and the 4,5-bis(dimethylamino)imidazolium triflates (IAr(NMe2)2)·HOTf is based on the coupling between the corresponding disubstituted formamidine and either an a-chloroacetamide for the mono-amino derivative or a reactive dichlorodiaminoethene for the bis-amino analogue. The electronic properties of the resulting new NHCs ligands have been studied by measurement of their Tolman Electronic Parameter (TEP) values obtained from the IR spectra of the complexes [Rh(IMesXY)Cl(CO)2] and by 77Se NMR spectroscopy of their corresponding selenoureas [(IMesXY)=Se]. It was shown that the electronic donation of the carbenic carbon sequentially increases by decoration with one or two amino groups respectively whereas the p-accepting properties of the NHC are only slightly or even not affected by the adjunction of the NMe2 groups on the imidazolyl backbone. Later, the synthesis of the two new PEPPSI-type palladium pre-catalysts PEPPSI-Pd-IPrNMe2 and Pd-PEPPSI-IPr(NMe2)2 were successfully achieved. From the calculated the percent buried volume %Vbur which is related to the steric properties of the two supporting NHC ligands, it appeared that grafting one amino group onto the backbone already leads to significant improvement of steric congestion while the second amino only results in a slight increase of the steric issue. The catalytic efficiencies of both pre-catalysts were evaluated in the benchmark Buchwald-Hartwig amination and compared with this of the reference PEPPSI-Pd-IPr. The bis-aminated pre-catalyst Pd-PEPPSI-IPr(NMe2)2 was shown to be the most active and stable pre-catalyst, and it was shown to be also highly efficient in more challenging amination reaction. It indeed allows to carry out the amination of aryl chlorides at low catalyst loadings or by using a mild base such as cesium carbonate, and even to activate the aryl tosylates, which are more difficult substrates than aryl chlorides. In order to study the critical stereoelectronic properties of the NHC ligands for the efficiency of the corresponding catalysts, further derivatization of the heterocyclic backbone was carried out, either by increasing the bulkiness of the mono-amino group from dimethylamino to diisopropylamino group to generate the carbene IArNiPr2, or by formally replacing one dimethylamino group by an halogen X in the bis-aminoimidazo-2-ylidene to give the carbenes IArNMe2,X. While the imidazolium salts (IArNiPr2)·HOTf was synthesized following the same method as (IArNMe2)·HOTf, the oxidative halogenation of the backbone of (IArNMe2)·HOTf with a N-halosuccinimide afforded (IArNMe2,X)·HOTf in good yields under very mild conditions. Noteworthy, this original reactivity was also observed on the rhodium and palladium complexes of this ligand
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Medley, Jonathan William. "Direct dehydrative N-Pyridinylation of amides, the interrupted Bischler-Napieralski reaction, and the enantioselective total synthesis and arylative dimerization of aspidosperma alkaloids." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/82319.
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Thesis (Ph. D. in Organic Chemistry)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
I. Direct Dehydrative N-Pyridinylation of Amides A method for the single-step N-pyridinylation of secondary amides is described. The process involves electrophilic activation of secondary amides with trifluoromethanesulfonic anhydride in the presence of 2-fluoropyridine followed by introduction of a pyridine N-oxide derivative and warming to afford the corresponding N-pyridinyl tertiary amide derivatives. The structure of activated amide intermediates is probed through in situ monitoring, and a mechanism supported by in situ monitoring and deuterium labeling experiments is discussed. II. Synthesis of Spirocyclic Indolines by Interruption of the Bischler-Napieralski Reaction The development of a versatile method for the synthesis of spirocyclic pyrrolidinoindolines is described. Treatment of N-acyltryptamines with trifluoromethanesulfonic anhydride-2-chloropyridine reagent combination affords highly persistent spiroindoleninium ions, which are selectively trapped intra- and intermolecularly by various nucleophiles. III. A Concise and Versatile Double-Cyclization Strategy for the Highly Stereoselective Synthesis and Novel Arylative Dimerization of Aspidosperma Alkaloids A strategy for the concise, stereoselective synthesis of aspidosperma alkaloids and related structures via a common putative diiminium ion intermediate is described. The approach enables the dimerization of aspidosperma-type structures at the sterically hindered C2-position. The diiminium intermediate is prepared in situ from an enantioenriched [alpha]-quaternary 2- chlorotryptamine lactam through a stereoselective electrophilic double-cyclization cascade. The key C5-quaternary stereocenter is secured via successive diastereoselective [alpha]-alkylations of pseudoephenamine crotonamide.
by Jonathan William Medley.
Ph.D.in Organic Chemistry
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Tomakinian, Terry. "Nouvelles méthodes de synthèse de benzofuroindolines. Vers la synthèse de la phalarine." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS031.
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Les benzofuroindolines forment une famille de composés qui se retrouvent sous deux formes : les benzofuro[2,3-b]indolines ou les benzofuro[3,2-b]indolines. Ce motif se retrouve dans de nombreuses molécules naturelles comme la bipleiophylline, la voacalgine A, le diazonamide A et la phalarine ce qui a mené à de nombreuses recherches pour leur synthèse. La biogénèse postulée est le couplage oxydant d'un indole et d'un phénol. Nous avons développé plusieurs voies d'accès à ces motifs en utilisant le noyau indolique. La première étude a consisté en un couplage oxydant direct entre un N-acétylindole et un phénol en présence de FeCl₃ et de DDQ. La méthodologie a montré sa généralité sur des dérivés d'indoles N-acétylés pour former en une seule étape des benzofuro[3,2-b]indolines. Dans certains cas, la benzofuro[2,3-b]indoline est obtenue si les groupements fonctionnels en position 2 et 3 sur l'indole sont identiques. Dans un but de synthétiser la phalarine, unique molécule naturelle contenant un motif benzofuro[3,2-b]indoline, nous avons réalisé une étape de C2-arylation d'un indole par un phénol à l'aide d'un couplage pallado-catalysé. La cyclisation à l'aide de NIS permet d'obtenir la benzofuro[3,2-b]indoline. L'ajout du carbone manquant de l'un des cycles est en cours d'étude par ajout d'un nucléophile monocarboné possédant un groupement partant. Par ailleurs, une dernière voie d'accès aux benzofuro[3,2-b]indolines a pu été mise au point par une réaction de Fischer interrompue. La réaction entre des benzofuran-3-ones et des arylhydrazines dans des conditions acides conduit aux benzofuroindolines souhaitées sous forme d'hémiacétals. La méthode a montré sa généralité et sa robustesse. Finalement, réaliser l'Umpolung de l'indole est un défi intéressant pour additionner des nucléophiles en position 3 de l'indole. Pour cela, des N-hydroxyindoles ont été synthétisés et l'utilisation de sels de biaryliodonium triflate a permis de réaliser une O-arylation. Le produit formé étant instable, il subit un réarrangement sigmatropique [3,3] pour conduire aux benzofuro[2,3-b]indolines désiréesBenzofuroindolines are a family of compounds which can be found in two regioisomeric forms: benzofuro[2,3-b]indolines or benzofuro[3,2-b]indolines. This core is present in several natural products such as bipleiophylline, voacalgine A, diazonamide A or phalarine which have been the subject of intensive efforts towards their syntheses. The postulated biogenesis is the oxidative coupling of an indole and a phenol. We developed four pathways to access these structures using the indole nucleus.The first part consisted in a direct oxidative coupling between a N-acetylindole and a phenol in presence of FeCl₃ and DDQ. This strategy showed its generality on N-acetylindoles derivatives to form in only one step the benzofuro[3,2-b]indoline core. In some cases, the benzofuro[2,3-b]indoline is obtained if the substitution in the C-2 and C-3 position is the same. In order to synthesize the phalarine, the unique natural product to possess a benzofuro[3,2-b]indoline core, we designed a C-2 arylation of an indole with a phenol using a palladium-catalyzed coupling. The cyclization steps using NIS led to the benzofuro[3,2-b]indoline core. The insertion of the missing carbon of one of the rings is under study by adding a nucleophile which contains only one carbon and a leaving group. The last strategy to access to benzofuro[3,2-b]indolines has been focused on an interrupted Fischer indolization. The reaction between benzofuran-3-ones and arylhydrazines in acidic conditions led to the desired benzofuro[3,2-b]indolines. This methodology is general and robust. Another part of the project was to achieve the Umpolung of the indole to add nucleophiles in C-3 position of the indole nucleus. N-hydroxyindoles were synthesized and the use of biaryliodonium triflate salts allowed an O-arylation reaction. The product being unstable, a [3,3] sigmatropic rearrangement can take place to afford the desired benzofuro[2,3-b]indolines
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Alsalim, Rana. "Contribution à la synthèse totale de la céphalotaxine." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114811/document.
Full textAbstract:
Depuis plus de 40 ans des chimistes se sont intéressés à l’extraction, à l’activité biologique et à la synthèse de l’homoharringtonine, un ester naturel de la céphalotaxine, qui est un puissant antileucémique, en vue de son utilisation thérapeutique, en particulier contre les leucémies résistantes aux inhibiteurs de tyrosine kinase. Ces alcaloïdes sont extraits de Cephalotaxus, des conifères originaires du sud de la Chine à croissance extrêmement lente et menacés d’extinction, la synthèse de ces alcaloïdes est nécessaire pour une utilisation thérapeutique.L’objectif de ce travail consiste à développer une synthèse concise de la (-)-céphalotaxine 1, afin de palier notamment le problème de sa pureté énantiomérique variable lorsqu’elle est issue de la matière première végétale. La stratégie développée dans ce travail nécessite d’effectuer un couplage de Heck avec des substrats désactivés et encombrés. Les résultats préliminaires ayant été décevants, le première objectif à consisté à développer l’utilisation de la méthode des plans d’expérience en synthèse totale, car l’efficacité de chaque étape a une répercussion importante sur le rendement en produit final. Dans une première partie, l’application d’un plan d’expériences a permis de pallier ce problème par une étude modèle pour déterminer les paramètres importants pour effectuer une telle réaction efficacement. Dans une deuxième partie, nous avons synthétisé les précurseurs et réalisé le couplage de Heck en vue de l’accès à un précurseur AC comportant tous les atomes de carbone du squelette de la céphalotaxine et les fonctionnalités requises pour sa cyclisation ultérieure en tétracycle ABCD. Enfin, nous avons fonctionnalisé les produits de Heck en position C3 par différents méthodes. Ces résultats ont permis de valider notre stratégie de synthèseFor more than 40 years the chemists were interested in the extraction, in the biological activity and in the synthesis of the homoharringtonine, a natural ester of cephalotaxine, which is a powerful antileukemic compound of therapeutic use, in particular against the leukaemia resistant to tyrosine kinase inhibitors. These alkaloids are extracted from Cephalotaxus, conifers native of the South of China with extremely slow growth. The objective of this work thus consisted in developing a concise synthesis of the cephalotaxine, to limit the recourse to the endangered vegetable resource The developed strategy requires an intermolecular Heck-coupling of electronically and sterically deactivated demanding substrates. The preliminary results having been disappointing, the first objective consisted in developing the use of the model of the experimental design in total synthesis because the classic methodology of variation of a single parameter at the same time said of "one by one" was ineffective. The application of a complete factorial design overcomes this problem by a model study, allowing to determine the optimized parameters to make this coupling reaction effective. We then synthesized the precursors from naturally abundant safrol and 2,3-butanedione then realized the Heck coupling with the aim of the access to the precursor AC containing all the atoms of carbon of cephalotaxine and the features required for its later cyclization in pyrrolobenzazepine ABC fragment. The o-iodized homopiperonylic alcohol led in certain conditions to an isochromane through a tandem Heck-oxa-Michael reaction. Finally, we have functionalized the Heck and hydro-arylation products obtained with 69-70 % yield in position C3 by different methods allowing us to validate our strategy to access these alkaloids
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Trejos, Alejandro. "Palladium-Catalysed Couplings in Organic Synthesis : Exploring Catalyst-Presenting Strategies and Medicinal Chemistry Applications." Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-173068.
Full textAbstract:
Palladium-catalysed coupling reactions have been embraced by synthetic chemists as one of the preferred means for smooth formation of new carbon-carbon bonds: a truly ubiquitous methodology of synthesizing complex molecules. This thesis describes the study of a series of palladium(0)-catalysed C2-arylations of a 1-cyclopentenyl ether, equipped with a chiral (S)-N-methyl-pyrrolidine auxiliary. The investigated olefin was demonstrated to undergo Si-face insertion, providing (R)-configuration of the arylated C2-carbon. In addition, the mild and novel palladium(II)-catalysed dominoHeck/Suzuki β,α-diarylation-reduction of a dimethylaminoethyl-substituted chelating vinyl ether was developed using arylboronic acids as arylating agents in combination with 1,4-benzoquinone (BQ). Further, highly regioselective palladium(II)-catalysed α-and β-monoarylation of the chelating vinyl ether was achieved using either a bidentate ligand or by employing ligand-less conditions. These studies demonstrate that the choice of ligands has a profound effect on the reaction outcome, as productive β,α-diarylation could only be obtained by suppressing the competing β-hydride elimination using BQ as the stabilising ligand and terminal reoxidant. The pivotal role of BQ in the reaction was studied using computer-aided density functional theory calculations. The calculations highlight the crucial role of BQ as a Pd(II)-ligand. In addition of serving as an oxidant of palladium, the calculations support the view that the coordination of BQ to the Pd(II)-centre in the key σ-alkyl complex leads to a low-energy pathway, aided by a strong η2 Pd-BQ donation-back-donation interaction. Furthermore, an investigation of the scope and limitations of novel stereoselective and BQ-mediated palladium(II)-catalysed domino Heck/Suzuki β,α-diarylation reactions, involving metal coordinating cyclic methylamino vinyl ethers and a number of electronically diverse arylboronic acids, conducted. In addition, a set of 4-quinolone-3-carboxylic acids, structurally related to elvitegravir and bearing different substituents on the condensed benzene ring, was designed and synthesized as potential HIV-1 integrase inhibitors. Finally, in an effort to identify a new class of HIV-1 protease inhibitors, four different stereopure β-hydroxy γ-lactam-containing inhibitors were synthesized, biologically evaluated, and co-crystallized with the enzyme.The time 12:05 for the public defense mentioned in the thesis is incorrect. It will take place at 09:15, 2012-06-08.
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Sarnpitak, Pakornwit. "Scaffold-oriented Synthesis for Drug Discovery." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/366103.
Full textAbstract:
The design and synthesis of three different scaffolds of nitrogen heterocycles have been achieved by using either methods described in the literature or newly developed synthetic methodologies/routes. The three synthesised libraries in this thesis were based on Pd-catalysed N-arylations, Castagnoli-Cushman multicomponent reaction, and Rh(II)-catalysed intramolecular C-H insertions. The compounds were successfully synthesised in moderate to excellent yields. Firstly, one of the synthesised diaryl imidazolines was found to be a selective COX-2 inhibitor due to its comparable activity to the approved drugs, celecoxib, and the binding mode was identical to the native ligand and other similar compounds. These observations are good starting points for the further development of selective COX-2 inhibitors based on imidazoline and related scaffolds. Secondly, the synthesis of novel scaffolds, pyrazino- and diazepino-fused isoquinolones, has been explored by using aryl glyoxals and diamines in the Castagnoli-Cushman multicomponent reaction, followed by post-MCR modifications. Unfortunately, all compounds in the library and their intermediates were inactive for antimicrobial activity. Moreover, the Rh(II)-catalysed intramolecular C-H insertion reactions of diazoesters to the C-H bond adjacent to the nitrogen atom yielded 2,3-disubstituted pyrrolidines. The selectivity of this reaction was influenced by the electron density of the C-H bonds undergoing insertion and steric hindrance around the reaction sites.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
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Eichhorst, Christoph. "Untersuchungen zur Synthese fluoreszenzaktiver aromatischer Polyzyklen durch Palladium-katalysierte Domino-C‒H-Aktivierungen." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-993C-7.
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Eriksson, Ludvig. "Transition Metal Mediated Transformations of Carboranes." Doctoral thesis, Uppsala University, Organic Chemistry, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3324.
Full textAbstract:
This thesis describes the use of copper and palladium to mediate transformations of carboranes, especially p-carborane.
1-(1-p-carboranyl)-N-methyl-N-(2-butyl)-3-isoquinolinecarboxamide, a carborane containing analogue of the peripheral benzodiazepine receptor (PBR) ligand PK11195, has been synthesised. A key step in the reaction is the copper (I) mediated coupling of p-carborane with ethyl 1-bromo-isoquinoline-3-carboxylate.
p-Carborane has been arylated on the 2-B-atom in high yields, using the Suzuki–Miyaura reaction. Thus the reaction between 2-I-p-carborane and various arylboronic acids [1-naphthyl-, phenyl-, 4-MeO-C6H4-, 3-CH3CONH-C6H4-, 4-NC-C6H4-, 3-NO2-C6H4-], gave the corresponding 2-aryl-p-carboranes in DME solution when reacted in the presence of cesium fluoride and the catalytic Pd2(dba)3–dppb system. Under the same conditions, the boron-boron bond forming reaction of two p-carboranylboronic esters (2-[(pinacolato)boron]-p-carborane and 2-[(neopentyl glycolato)boron]-p-carborane) was also shown feasible.
p-Carborane has been vinylated on the 2-B-atom in high yields by use of the Heck reaction. The coupling between 2-I-p-carborane and various styrenes [4-H-, 4-C6H4-, 4-Cl , 4-Br-, 4-NO2-, 4-CH3O- and 4 CH3 ] resulted in the formation of the correspondingtrans-β-(2-B-p-carboranyl) styrene in DMF solution when reacted in the presence of silver phosphate and the palladacycle Herrmann´s catalyst. The reaction was shown to proceed at higher rate with electron rich than with electron deficient olefins.
The feasibility of palladium-catalysed isotopic exchange of an iodinated closo-carborane with a radioisotope of iodine has been studied. 2-I-p-carborane was selected as a model compound. It was shown, that such isotopic exchange is possible and provides a high yield (83 ± 4.2 %) during 40 min long reaction. The reaction conditions were optimised, and it was demonstrated that presence of the tetra n-butylammonium hydrogensulphate is important in order to stabilise catalyst and provide reproducibility of labelling. In this work we have modified the methodology and extended the application to a wider range of iodinated carboranes. By the use of Herrmann’s catalyst in toluene at 100 °C this [125I]-iodide labelling could be improved and extended. 2-I-p- 9-I-m-, 9-I-o-, 3-I-o-carborane, 1-phenyl-3-I-o-carborane and 1,2-diphenyl-3-I-o-carborane could be [125I]-iodide labelled in high to excellent yields within 5 minutes.This reported palladium catalyzed radio-iodination of the uncharged closo-carboranes might find use in pharmacokinetic studies of carborane derivatives.
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Ciccolini, Cecilia. "Synthesis of Mono and Poly-Heterocycles starting from 1,2-Diaza-1,3-Dienes (or precursors) as Building Blocks." Doctoral thesis, Urbino, 2020. http://hdl.handle.net/11576/2674162.
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BELLOSTA, DECHAVANNE VERONIQUE. "Contribution a l'etude de la reactivite de derives glucidiques vis-a-vis d'organometalliques : nouvelles syntheses stereospecifiques de c-glycosides." Paris 6, 1987. http://www.theses.fr/1987PA066256.
Full textAbstract:
Deux nouvelles methodes de syntheses stereospecifiques de desoxy-2 c-glucosides possedant une fonction ester d'enol sont presentees : - l'addition conjuguee d'organocuprates cyanes sur des hexeno-1 pyrannuloses-3 peracetyles (l'anhydride acetique piegeant l'enolate intermediaire) permet d'obtenir des aryl-alpha -d-c-glycosides. Cette methode est detendue avec succes en serie furannose; - l'arylation de glycals catalysee par des sels de palladium fournit les composes voulus en une seule etape a partir de derives glucidiques commerciaux. L'etude de la configuration des c-glycosides obtenus est effectuee et de nombreuses donnees structurales sont exposees
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"Platinum and palladium complexes in arylation and silicone-forming reactions." Tulane University, 2001.
Find full textAbstract:
Three new platinasilanols---(dcpe)Pt(SiR2OH)(H) (where dcpe = 1,2-bis(dicyclohexylphosphino)ethane] and R = tBu, iPr, or mesityl)---have been synthesized by reacting (dcpe)PtH2 with the corresponding hydrosilanol, HSiR2OH. An X-ray crystal structure of (dcpe)Pt(SitBuOH)(H) was determined. Addition of McLi to the tBu derivative yields what appears to be the deprotonated platinasilanol. The tBu derivative can be converted into the platinasilatriflate by addition of triflic anhydride in the presence of 2,2,6,6-tetramethylpiperidine. The neutral platinum species does not catalyze the formation of a silanone with ditert-butylsilanol but does react in a stoichiometric fashion with diisopropylsilanol to give hexaisopropylcyclotrisiloxane The synthesis of [(dcpe)Pt(CH2Cl2)(Me)] +MeB(C6F5)3- was accomplished by the reaction of (dcpe)PtMe2 with B(C6 F5)3 in CH2Cl2. This cation was found to catalytically convert HSitBu 2OH into HSitBu2OSi tBu2OH and MeSitBU 2OSitBU2OH, which are trapping products indicative of a silanone intermediate (tBu 2Si=O) being formed. [(dcpe)Pt(mu-H)2Pt(dcpe)][2MeB(C 6F5)3] is formed as the only phosphorus containing species in this reaction [(dcpe)Pt(mu-H)2Pt(dcpe)][2MeB(C6F5) 3] can also be formed from the reaction of [dcpePt(CH2Cl 2)(Me)]+MeB(C6F5)3 - with H2 gas. An X-ray crystal structure was determined for the dimer from a crystal grown in a mixture of wet CH2Cl 2 and pentane. The crystal grown, [(dcpe)Pt(mu-H)2Pt(dcpe)][2[HOB(C 6F5)3] is the first known example of a dicationic transition metal species with hydroxy-tris(pentafluorophenyl)borate as the anionic species. When a catalytic amount of [(dcpe)Pt(mu-H)2Pt(dcpe)][2MeB(C 6F5)3] is reacted with HSiiPr 2OH, the cyclosiloxanes (iPr2SiO) 3, 4, an insertion product HSiiPr 2OSiiPr2OH, and the condensation product HSiiPr2OSi iPr2H are formed. Formation of the insertion and cyclic products give strong evidence that a silanone intermediate was generated The complex [dcpePd]2 was generated in situ by the reaction of (dcpe)PdCl2 and N2H4. Ortho-, meta- and para-derivatives of chlorobenzene were reacted with [dcpePd]2 to yield the corresponding dcpePd(Ar)Cl oxidative addition products. An X-ray crystal structure for (dcpe)Pd( o-tolyl)(Cl) is reported Bis(phosphino)ethane derivatives---R2PCH2CH 2PR2 (where R = Cy, iPr, or Ph)---have been prepared using a three step synthesis. First, two equivalents of the corresponding R2PCl is reacted with HOCH2CH 2OH in the presence of a base to yield R2POCH2CH 2OPR2. When heated, this bis(phosphite) undergoes thermal Michaelis-Arbusov rearrangement to form the bis(phosphine oxide)---R 2P(O)CH2CH2(O)PR2. A DSC study yield the heat of isomerization of the cyclohexyl derivative to be -40.4 +/- 0.6 kcal/mol. Finally, reduction of the phosphine oxide by HSiCl3 yields the phosphine in good overall yield for the isopropyl and cyclohexyl derivatives (61% and 75%, respectively)acase@tulane.edu
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Nath, Dinesh. "Metalated Nitriles: Ligand Exchange and Copper-Catalyzed Reactions." 2013. http://digital.library.duq.edu/u?/etd,162308.
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This thesis describes new methods of carbon-carbon bond formation using metalated nitriles generated via metal exchange reactions. Sulfinylnitriles undergo a sulfinyl-metal exchange to yield lithiated, magnesiated and zincated nitriles, which can trap a range of electrophiles. The sulfinyl-metal exchange is effective with vinylic, quaternary and tertiary substitution patterns and addresses the long-standing problem of alkylating secondary nitriles. This method was then further extended to other oxidation states of sulfur, namely sulfonyl-metal exchange and relatively unknown sulfide-metal exchange. The sulfide metal exchange overcomes the problem related to the propensity of highly substituted sulfinylnitriles to eliminate. Sulfide-metal exchange is synthetically attractive because of the numerous methods for generating arylsulfides and the high tolerance of arylsulfides to numerous reagents. <br>A copper-catalyzed arylation reaction of aryl iodides and metalated nitriles was developed using catalytic Cu (I) and an amine ligand. A proof of principle has been established, providing a sound basis for developing the reaction. A new strategy has been developed for alkylation of alkenenitrile using LDA as base in presence of catalytic CuCN. Subsequent trapping with an electrophile, affords alkylated alkenenitriles in which the olefin is no longer in conjugation with the nitrile. <br>The distinct structural differences between N- & C-metalated nitriles have been harnessed in a series of chemoselective alkylations. Lithiated nitriles are found to be particularly reactive toward alkyl halides whereas magnesiated nitriles react selectively with oxygenated electrophiles. Using this strategy allows chemoselective alkylation of metalated nitriles.Bayer School of Natural and Environmental Sciences;
Chemistry and Biochemistry
PhD;
Dissertation;
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Wheelhouse, Richard T., and D.-F. Shi. "Novel, High-yielding Synthesis of meso-Substituted Porphyrins via the Direct Arylation of Porphine." 2002. http://hdl.handle.net/10454/3620.
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NoA new method for the synthesis of meso-substituted porphyrins is described: reaction of 5,10,15,20-tetrabromoporphine magnesium complex with aryl or heteroaryl boronic acids in the presence of Pd(PPh3)4 gave meso-substituted porphyrins in yields up to 70%.
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Rippel, Rafael Alves. "Exploring The benziodoxole Chemistry: New Routes for old Reactions." Master's thesis, 2017. http://hdl.handle.net/10362/25690.
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Peng, Yi-Kai, and 彭奕愷. "Facile Synthesis of Benzotrithiophene-Centered HTMs for Perovskite Solar Cells by Pd-Catalyzed C-H Activation/Arylation Reactions." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/5panp9.
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碩士國立中央大學
化學工程與材料工程學系
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We develop new benzotrithiophene (BTT)-base hole-transporting materials, synthesized by 3-fold C-H/C-Br cross-couplings. We use benzotrithiophene as middle core and 3,4-ethylenedioxythiophene (EDOT) as π-linker. In the end group, we use triphenylamines as donors. The reaction conditions have been optimized by several entries and all HTMs have good yields. Perovskite solar cells based on the new HTM YKP03, which has EDOT as π-linker, achieve 14 % of power conversion efficiency with dopants and get over 13 % of PCE under dopant-free condition. Another HTM YPK05, which has t-butyl groups as function groups, shows great thermal stability and gets over 15 % of PCE in perovskite solar cells. These results indicate that the new HTMs have potential to be used in perovskite solar cells due to the less synthetic steps and avoiding to use hygroscopic dopants, making the elements become more economical and more stable comparing with the normally used HTM Spiro-OMeTAD.
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Friedman, Adam Alexander. "Rhodium and Palladium Catalysed Domino Reactions of Alkenyl Pyridines and Alkenyl Pyrazines." Thesis, 2013. http://hdl.handle.net/1807/42841.
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Domino catalysis is an ideal strategy in the synthesis of heterocyclic scaffolds, as multiple bonds can be formed under a single set of reaction conditions. In this work, we present the development of two novel domino processes which afford access to aza-analogues of the dihydrodibenzoxepine motif. Careful optimisation revealed that the Rh catalysed hydroarylation proceeds under mild conditions as compared to the C-O coupling. Furthermore, Pd was not required for the C-O bond formation when using alkenyl pyrazines as substrates. Variation of the substituents on both the heterocycle and on the boronic ester provided insight into the structural features required for successful domino reaction, and a stepwise protocol was developed for incompatible substrates. We have also developed the first multi-metal, multi-ligand domino reaction featuring both a chiral and achiral ligand in the same pot, still leading to an enantioenriched product.
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Bugarin, Cervantes Alejandro. "Metal-Catalyzed Carbon-Carbon Bond Forming Reactions for the Synthesis of Significant Chiral Building Blocks." Thesis, 2011. http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9390.
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Morita Baylis-Hillman (MBH) reaction a carbon-carbon bond forming reaction
between an α,β-unsaturated carbonyl and aldehydes or activated ketones in the presence
of a nucleophilic catalyst. The MBH reaction is an atom-economical method of rapid
increase of molecular complexity. The development of this process has received
considerable attention in recent years. This dissertation presents the development of a
new catalytic system for the symmetric and asymmetric MBH reaction. The new system
for the racemic version of this reaction was accomplished employing a 1:1:1 ratio of
catalytic amounts (10 mol%) of MgI2, TMEDA and DMAP and proved to be highly
effective. For the asymmetric version was developed a highly enantio-selective system
based on Fu’s planar chiral DMAP derivative (II) with ee´s up to 98%. Abnormal MBH
adducts are obtained employing either ethyl 2,3-butadienoate or ethyl propiolate in good
yields, in the presence if MgI2 and either a tertiary amine or phosphine as the
nucleophile. The α,β-unsaturated carbonyls where prepared by a modified direct α-
methylenation using paraformaldehyde, diisopropylammonium trifluoroacetate, and
catalytic acid or base with excellent yields for several carbonyls compounds.
The Negishi cross-coupling reaction is the Pd or Ni-catalyzed stereoselective
cross-coupling or organozincs and aryl-, alkenyl-, or alkynyl halides. Enantioselective
Negishi cross-coupling of aryl zincs and α-bromo ketones was accomplished employing
a NCN Pincer complex as the catalyst with ee´s up 99%. The required pincer complexes
have been prepared by the oxidative addition of pincer ligands with palladium or nickel.
Additionally, It has been developed a direct and highly active, (NCN)-Pd
catalytic system for the α-arylation of ketones with a variety of aryl bromides using the
air and moisture stable [t-BuPheBox-Me2]PdBr (XVI) as the catalyst. The adducts are
obtained in excellent yields (92% average for 20 examples) in only 1 hour using 1 mol%
of catalyst loading. Perhaps more importantly, the work described here shows that XVI
is highly reactive, highly selective, even on substrates bearing challenging functional
groups such alkenes.
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Li, Da. "Transition metal-free desulfinative cross-coupling of 2-pyridyl sulfonates with organolithium reagents : mild access to 2-substituted pyridines." Thesis, 2021. http://hdl.handle.net/1866/25438.
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Le motif biaryl contenant la pyridine représente une structure omniprésente dans la chimie organique et médicinale. Ainsi, le développement de méthodes fiables de synthèse est continuellement désiré. Traditionnellement, les cycles azotés biarylés sont efficacement synthétisés par des réactions de couplage croisé catalytique. Cependant, la pyridine peut être difficilement fonctionnalisée en position C-2 compte tenu de sa déficience en électrons. Cette propriété limite son utilisation en tant que partenaire nucléophile dans les réactions de couplage croisé. Par exemple, dans le couplage de Suzuki-Miyaura, l’acide 2-pyridyle boronique est connu pour son instabilité. À l’inverse, les organométalliques du 2-pyridyle sont peu réactifs pour faire des réactions de substitution aromatique électrophile. La synthèse des pyridines 2-substituées est par conséquent un défi qui reste difficile à relever.
La première partie de ce mémoire est consacrée au développement récent des méthodes pour résoudre les problèmes de couplage avec des nucléophiles 2-pyridyles. En particulier, les approches classiques comme le couplage modifié de Suzuki-Miyaura, l’activation de liaison C-H des composés pyridinium N-activés, et l’arylation directe du cycle pyridine sont présentées. De plus, les approches alternatives qui utilisent la partie pyridine comme partenaire électrophile dans la réaction couplage avec les réactifs organométalliques sont également discutées.
Dans la deuxième partie de ce mémoire, une méthode de couplage croisée entre des esters de sulfonate de 2-pyridyles et des organolithiens est rapportée. Une variété de pyridines 2-substituées a été synthétisées avec succès en faisant réagir des sulfonates de pyridine avec des organolithiens (aryl, alkane, heteroaryle lithium) à basse température. La méthode permet également de s’affranchir de l’utilisation d’un quelconque métal de transition. Des études mécanistiques montrent que le processus impliquant les composés lithiés s’apparente à une réaction de substitution nucléophile aromatique. Cependant, le mécanisme diffère lorsque la réaction met en jeu des réactifs de Grignard, où un processus de couplage entre deux ligands d’un intermédiaire σ-sulfurane peut être impliqué.Biaryl compounds containing the pyridine moiety represent a ubiquitous structure in both organic and medicinal chemistry. Therefore, finding new and reliable approaches for their synthesis is still of interest. Traditionally, azine containing biaryls are efficiently synthesized via transition-metal catalyzed cross-coupling reactions. However, due to its π-deficient nature, pyridine cannot be easily functionalized at the C-2 position to serve as nucleophile partner. For examples, in the Suzuki-Miyaura cross-coupling reaction, 2-pyridyl boronates are well known for their instability. 2-Pyridyl organometallics undergo electrophilic aromatic substitution poorly. Thus, the synthesis of 2-substituted pyridines remains a challenging task. The first part of the thesis focuses on the recent methods to address the coupling issues of 2-pyridyl nucleophiles in cross-coupling reactions. Of note, the classical methods including Suzuki-Miyaura cross-coupling reactions, C-H activation of N-activated pyridinium species, and direct coupling reaction of pyridine are presented. Alternative approaches using the pyridine moiety as an electrophilic entity in the coupling with organometallic reagents are also discussed. In the second part of the thesis, a transition metal-free desulfinative cross-coupling reaction of 2-pyridyl sulfonates with organolithium reagents is reported. A variety of 2-substituted pyridines were successfully synthesized in good yields, by treatment of neopentyl 2-pyridyl sulfonates and phenyl 2-pyridyl sulfonate with aryl, alkyl, and heteroaryl-lithium reagents at low temperature. Mechanistic studies showed that the coupling reaction with lithium reagents undergoes an SNAr pathway. However, a ligand coupling process of a σ-sulfurane intermediate may be involved in the reaction with Grignard reagents to form the biaryl.
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Lee, Yan-Yi, and 李衍毅. "The Use of Isomeric Normal and Abnormal Palladium NHC Complexes in Direct C5-arylation Reaction." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/3fes4m.
Full textAbstract:
碩士國立彰化師範大學
化學系
106
We designed four series of isomeric palladium(II) complexes normal and abnormal N-Heterocyclic Carbenes (NHCs) ligands. These complexes were characterized by 1H and 13C NMR spectroscopy, elemental analysis and X-ray crystallography. Their potential application as catalysts in direct C5-arylation reaction between imidazoles and aryl halides were investigated. Using a mere 0.5 mol % Pd loading, coupled products were obtained with moderate to excellent yields. Normal NHCs complexes have better catalytic activity than their abnormal counterpart. DFT calculations were performed to explain the difference.
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Lin, Wu-Shien, and 林武賢. "Palladium Complexes with N-heterocyclic Carbene and Phosphine Ligands: their Catalytic Application in Direct Arylation Reaction." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/80528611956437786449.
Full textAbstract:
碩士國立彰化師範大學
化學系
98
The new palladium complexes with NHC and phposphine ligand, PdR2(NHC)(PR'3) were prepared from the reactions between ligand precursors with different steric effect and PdCl2(COD). New derivatives were prepared by the ligand substitution reaction between PPh3 and PCy3, bipyridine, and acetate. All the complexes were successfully characterized by X-ray crystallographic studies and NMR, illustrating the structural difference due to the ligand structures. Interesting intramolecular interactions were found in some of these complexes. To understand the relative stability between the cis and the trans forms, we conducted density functional theory computations. In catalytic investigations, the new complexes were test as precatalysts for Suzuki, Heck coupling reaction, and direct arylation reaction. Unfortunately the yields were not good in Suzuki coupling reaction; the working temperature was too high. But we get outstanding yields in direct arylation reactions. Initially, complexes were screened as precatalysts for the direct arylation reactions between aryl halides and alkynes. Then we utilized wide scope of reactants to test our compounds’ activities. Excellent performance was achieved. We also tested new direct arylation reactions using imidazole derivatives, and proved that the complexes were also quite effective. In short, we find these complexes having remarkable success in direct arylation reactions.
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Hou, Wen-Yi, and 侯文易. "Palladium-Catalyzed α Arylation Reaction of Cyclic Vinylogous Esters: Total Syntheses of Aromatic Podocarpane-type Diterpenoids." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/99977t.
Full textAbstract:
碩士國立交通大學
應用化學系碩博士班
105
The first part of this thesis describes palladium-catalyzed α-arylation reaction of cyclic vinylogous esters. The commercial 1,3-cyclohexedione (81) was undergo three times alkylation on the different atoms of compound 81 to get the vinylogous esters 86. We examined several reaction parameters and found the optimal condition called for the combination of Pd(dba)2 and tBuP3 and lithium dicyclohexylamide acting as a base. The optimized conditions were utilized to conduct the coupling reaction between a vinylogous ester and bromoarenes. Electron-deficient and Electron-rich bromoarenes were effective coupling partners, the corresponding products are compound 100～106. It is noteworthy that the arylation is compatible with a sterically demanding ortho-substituted substrate, albeit at a slower rate (compound 107). We examined the compatibility of heterocyclic bromides in this transformation and it can be applied with good yield and the corresponding products are compound 108～112. The second part is describle total syntheses of aromatic podocarpane-type diterpenoids. A conjugated dienone 145 was prepared from the arylated product 104 via a Stork−Danheiser transposition that comprises sequential 1,2-addition of vinylmagnesium bromide and acidic hydrolysis. Lewis acid-promoted intramolecular Friedel−Crafts reaction of the dienone 145 led to the formation of a tricyclic compound 146. Reductive alkylation of the tricyclic compound under birch conditions provided the desired trans-decalin system bearing the gem-dimethyl moiety 142. Then, the facile removal of the O-methyl group with boron tribromide delivered racemic 12-hydroxy-13-methylpodocarpa-8,11,13- trien-3-one (133). Following reduction in excellent diastereoselectivity, thus accomplishing the first total synthesis of racemic 3β,12-dihydroxy-13-methyl -podocarpane-8,11,13-triene (134). Finally, we showed that (±)-O-methyl nimbinone (135)could be prepared via benzylic oxidation of compound (±)-142.