The increasingly complex world of illicit chemistry has created a need for rapid, selective means of determining the threat posed by new drugs as they are encountered by law enforcement personnel. To streamline this process, the entirety of the problem, from the production of illicit drugs all the way to the final analysis have been investigated. A series of N-alkylated phenethylamine analogues were synthesized in a shotgun method and subjected to direct-infusion analysis. A range of products were detected without the need for time-consuming purification steps, which was extended to novel pharmacological and receptor-binding assays where mass spectrometry is used as a detector. This direct-infusion technique was also applied to studies of methamphetamine and fentanyl production to preemptively determine improvements to common reaction conditions and explore the origins of common impurities. The ability to utilize these rapid techniques directly from the fume hood has also been critically reviewed to highlight gaps in current research and opportunities for improvement. When combined, these studies seek to provide a means for rapid, simplified analysis of illicit drugs to improve the quality of data and dramatically increase throughput.

Les transistors organiques à effet de champ (OFETs) dans lesquels le transport des charges se fait à travers un film mince de molécules organiques représentent une transformation de la technologie des transistors à effet de champ au regard de la technologie au silicium. Ils permettent notamment d’envisager le développement d’une électronique flexible à bas coût. Ce travail porte sur la synthèse, l’étude et l’utilisation en tant que couche active dans des OFETs de type n de couples d’isomères para- et méta-indacénodithiophènes (para- et méta-IDT) appauvris en électrons inédits. Une introduction aux OFETs de type n est tout d’abord présentée. Elle est suivie par la présentation de la synthèse des dérivés IDT et de l’analyse comparée de leurs propriétés physico-chimiques. La fabrication des OFETs, leur caractérisation et l’optimisation de leur architecture est enfin décrite, leurs performances montrant l’intérêt des IDTs pour les OFETs de type n. Différentes fonctionnalisations menant à des IDTs d’architecture 3π-2spiro sont également synthétisées afin d’étudier les propriétés intrinsèques de ces dérivés π-conjugués et d’envisager leur incorporation comme matrice hôte dans des diodes électrophosphorescentes organiques. / Organic Field Effect Transistors (OFETs), in which the charge transport is carried through a thin film made of organic molecules represent a transformation of the FET technology regarding that based on Silicon. They offer in particular the possibility to manufacture low cost flexible electronics. This work is focused on the synthesis, the study and the use as active layer in n-type OFETs of novel, electron poor, couples of para- and meta-indacenodithiophenes isomers (para- and meta-IDT). First of all, an introduction to the field of n-type OFETs is presented, followed by the presentation of the synthesis of the IDT derivatives and the comparative analysis of their properties. Finally, the fabrication of the OFETs, their characterization and the optimization of their architecture is described. The performances recorded attest that these derivatives are of great interest for the n-type OFETs. Different 3π-2spiro IDT derivatives are also presented in order to study the IDTs intrinsic properties and to envisage their incorporation as host in phosphorescent organic light-emitting diodes.

This work consists of four consecutive parts, each dealing with syntheses of structurally diverse compounds. The syntheses were based on the methods within the domain of transition-metal catalyzed and/or mediated reactions with particular emaphasis on the application of organozirconium chemistry. 1. A method for synthesis of tricyclic condensed hydrocarbons possessing 5(6)-7-6(aryl) framework was developed. It is based on reaction of bicyclic zirconacyclopentenes, prepared by oxidative dimerization of enynes on a low-valent zirconocene species (Negishi's reagent), with ortho-halobenzaldehydes in the presence of various additives. The presence of two different centers of reactivity - the sp2 C-Zr and sp3 C-Zr bond - allowed sequential functionalization of each bond. Thanks to its higher nucleophilicity, the sp3 C-Zr bond reacted preferentially with the carbonyl carbon of the aldehyde yielding an oxazirconacycloheptene. The subsequent transmetallation of the remaining sp2 C-Zr bond with CuCl in the presence of other additives (catalysts) enabled an intramolecular cross-coupling reaction with the aryl halide moiety furnishing the desired tricyclic products in reasonable yields. The scope of the reaction with respect to differently functionalized reactants was assessed, as well as its mechanistic...

The current methodologies of catalytic enantioselective allylation of aldehydes were studied on conjugated dienals and later on haloacrylaldehydes as the substrates. The resulting enantioenriched homoallylalcohols were prepared by reactions promoted either by commercial Brønsted acid catalysts or by Lewis base catalysts developed by our group, often with high enantio- and diastereoselectivities. Subsequently, the methodology was expanded on catalytic enantioselective crotylation and pentenylation reactions, practically unknown not only with these substrates. The applicability of this synthetic approach was demonstrated on preparation of several natural products or their intermediates.

2,2'-Bipyridines and their appropriate N,N'-dioxides form a significant class of heteroaromatic compounds, which has found application in various fields of chemistry and predominantly in asymmetric catalysis. One of the most powerful methods for their synthesis is cocyclotrimerization of alkynes with nitriles. A new variant of cyclotrimerization reaction - cocyclotrimerization of halodiynes with nitriles, which results in the formation of 2- and 3-halopyridines, has been developed. The reaction was studied on a wide range of substrates providing the pyridine products in good isolated yields. Formation of an unexpected product of halogen exchange reaction was observed during the course of the study and its origin was elucidated by experimental studies. The prepared 2-halopyridines were used as starting materials for syntheses of new chiral 2,2'-bipyridine ligands. The crucial step of their synthesis turned out to be the reductive dimerization of 2-halopyridines to the corresponding 2,2'-bipyridines. Application of the formed bipyridine ligands was then tested in various metal-catalyzed asymmetric reactions, namely Mukaiyama aldol reaction, hydroxymethylation, conjugate addition, C-H activation of indole and desymmetrization of meso-epoxides, in which one of the bipyridine ligands showed...

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Bimetallic Catalysis is an emerging field of study that uses two metals to cooperatively perform organic transformations. These metals can serve to activate or bind substrates in order to increase the rate and selectivity of reactions. This work first describes the synthesis and utilization of six new chiral, titanium-containing phosphinoamide ligands. These Lewis acidic ligands withdraw electron density from an active palladium center to induce chirality and increase the rate of allylic amination of hindered, secondary N-alkyl amines. X-ray quality crystals were grown for each ligand and completed the allylic amination of hindered secondary amines in minutes whereas other non-titanium-containing ligands produced trace product. Although enantioselectivity was low initially, through a dynamic kinetic resolution enantioselectivity was increased over time, reaching 53% enantioselectivity. The second type of bimetallic catalysis discussed is dinuclear Pd(II) and Pd(I) catalysis. These dimers were built on a 2-phosphinoamide ligand scaffold and present interesting molecular structure and unique reactivity. These dimers were found to perform tandem arylketone coupling to produce disubstituted naphthalene products under oxidative conditions. It is proposed that the Pd(II) dimer undergoes oxidative addition to produce a Pd(III) dimer which subsequently produces an aryl-ketone intermediate. This process is made possible by the cooperativity of the two palladium centers which enable the formation of a Pd(III) dimer, circumventing the need for the high energy Pd(IV) oxidation state. Oxidative conditions then allows coupling and cyclization of a second ketone to form the naphthalene product.

La découverte et l’étude de versions stables d'intermédiaires réactionnels, tels que les radicaux ou les carbènes stables, ont eu un impact profond sur la chimie moderne. Non seulement ces composés ont permis, sur le plan académique, l’émergence de nouveaux concepts et une compréhension plus approfondie d’importantes questions fondamentales, mais ils ont également ouvert la voie au développement d’applications pratiques originales et innovantes.Les oxyallyles sont des intermédiaires réactionnels typiques, postulés dans plusieurs transformations chimiques mais longtemps considérés comme non-isolables, voire non-observables. Cependant, des résultats préliminaires à nos travaux démontraient que la conception de versions stables était envisageable grâce à l’introduction de groupements donneurs aminés.Ce travail de thèse a porté sur le développement de méthodologies de synthèse de motif organiques de type 1,3-di(amino)oxyallyles. Le premier chapitre bibliographique résume 40 ans de tentatives d’observation d’oxyallyles transitoires ou de dérivés stabilisés.Le chapitre suivant décrit nos efforts pour synthétiser des dérivés 1,3-di(amino)oxyallyles par oxydation directe de sels de vinamidiniums. Cette approche a conduit à la génération du radical cation du tetrakis(dimethylamino)oxyallyle qui, malgré un faible encombrement stérique, est persistent plusieurs heures en solution aérée.La troisième partie explore une méthodologie alternative, basée sur l’utilisation de groupes protecteurs. Cette voie complémentaire a notamment permis la synthèse et la caractérisation de dérivés d’oxydes de pyrazolium, des colorants proposés et étudiés théoriquement, mais jamais synthétisés et dont la possible existence était mise en doute.Enfin la dernière partie se consacre à la conception de carbènes stables originaux et de leurs dérivés, avec en perspective leur utilisation comme ligands redox actifs. En particulier, nous décrivons la synthèse et l’étude du premier 1,3-pyrimidinium-2-ylidène stable, ainsi que l’oxyde correspondant : formellement un oxyallyle fusionné à un amidinium, mais parfaitement stable à l’air. / The discovery and the study of stable versions of reactive intermediates, such as radicals or carbenes, have had a deep impact on modern chemistry. Those compounds have not only allowed for the rise of new academic concepts and deeper understanding of fundamental questions, but they also paved the way for the development of innovative and original applications.Oxyallyls are typical elusive intermediates, postulated in several chemical reactions, though they had been considered as non-isolable, and even non-observable for a long time. However, preliminary results to our work demonstrated that enhanced stabilization could be achieved by introducing electron-donating amino groups.This work focused on the development of a methodology for the synthesis of organic 1,3-di(amino)oxyallyl patterns. The first chapter summarizes 40 years of attempts for the observation of transient oxyallyls and stabilized derivatives.The following chapter describes our efforts to synthesize 1,3-di(amino)oxyallyl derivatives by direct oxidation of vinamidinium salts. This approach afforded the generation of the tetrakis(dimethylamino)oxyallyl radical cation, which, despite a small steric hindrance is persistent for hours in aerated solutions.The third part explores an alternative methodology, based on the use of protective groups. It enabled the synthesis and the characterization of a pyrazolium oxyde derivative, which has been proposed theoretically, but never synthesized, and whose existence was even questioned.Finally, the last chapter describes the conception of original stable carbenes and their derivatives, with their use as redox non-innocent ligands in perspective. In particular, we report the synthesis and the study of the first stable 1,3-pyrimidinium-2-ylidene, as well as its corresponding oxide: formally an oxyallyl fused with an amidinium, but perfectly stable towards air.

L'utilisation du cobalt en synthèse et catalyse organiques est reconnue depuis les années 1970, notamment dans la réaction de Pauson-Khand. Dès lors, de nombreux systèmes catalytiques au cobalt ont prouvé leur efficacité dans diverses transformations chimiques telles que les cycloadditions [2+2+2] ou l'activation des liaisons C(sp2)-H. Dans ce manuscrit, sont présentés des transformations chimiques basées sur l’utilisation de catalyseurs au cobalt s’effectuant essentiellement avec économie d’atomes, et les essais de développement des versions énantioselectives.Tout d'abord, l'activité de catalyseurs au cobalt(I) a été établie dans la réaction de cycloisomérisation de diènynes pour obtention de bicycles[4.3.0]. Les études concernant différents paramètres du système catalytique ainsi que le champ d'application sont présentés. Les catalyseurs à base d'acétate de cobalt(II) se sont révélés très efficaces pour les réactions d'hydroalcynylation. L'hydroalcynylation de vinylaziridines a été développée après optimisation du système catalytique et, le domaine d’application selon la nature des réactants a été défini. Finalement, les études préliminaires de l'allylation énantiosélective avec les catalyseurs de cobalt(II) ont été réalisées. Ceux-ci se sont révélés plutôt comme activateurs du groupement carbonyle, compromettant la version asymétrique de la réaction / The application of cobalt in organic synthesis and catalysis has been known since the 1970s, especially in Pauson-Khand reaction. Until now, a lot of catalytic systems with cobalt have demonstrated their efficiency in various chemical transformations including [2+2+2] cycloadditions or the activation of C(sp2)-H bonds. In this manuscript are presented the chemical transformations based on the use of cobalt to catalyze atom-economical reactions, and the attempts to develop enantioselective versions. First of all, the activity of cobalt(I) catalysts was established for the cycloisomerisation reaction of dienynes giving bicycles[4.3.0]. The studies of different parameters of the catalytic system, as well as the scope reaction, will be presented. Moreover, the catalysts based on cobalt(II) acetate proved to be very efficient for hydroalkynylation reactions. The hydroalkynylation reaction of vinylaziridines was developed after catalyst optimisation and, the scope reaction according to the nature of reactants was defined. Finally, preliminary studies of enantioselective allylation using cobalt(II) catalysts were performed. These promoters were found to be activators of the carbonyl group, thus compromising the asymmetric version of the reaction

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19239号 / 工博第4074号 / 新制||工||1628(附属図書館) / 32238 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 村上 正浩, 教授 吉田 潤一, 教授 松田 建児 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM