Organosulfur plays a significant role in synthetic chemistry. In particular α,β-unsaturated sulfides (i.e. vinyl sulfides) are versatile building blocks that exhibit untapped potential in reaction development. This thesis focuses on reaction development in this space. Chapter 1 discusses the characteristics that sulfur attributes to organic molecules followed by a review of synthetic preparations and applications of vinyl sulfides. Chapter 2 discusses the development of a formal-phosphorus Pummerer reaction enabling simple access to thiophosphonium Wittig reagents. These thiophosphonium salts are used to access a library of vinyl sulfide substrates that are further hydrolyzed to the corresponding ketones. This two-step sequence enables a strategic approach affording aldehyde to ketone homologation via vinyl sulfide intermediates, enabling access to synthetically challenging α-aryl ketones. Chapter 3 discusses the direct use of vinyl sulfides as carbonyl surrogates in Fischer indole reactions. Vinyl sulfides are demonstrated to be aldehyde and ketone surrogates in the preparation of diverse 3-substituted and 2,3-disubstituted indoles or azaindoles. The utility of this chemistry is shown with the preparations of three biologically significant compounds: 4-aza-melatonin, a furoindoline scaffold and an indomethan-like CRTh2 anatagonist. Chapter 4 showcases the first total synthesis of a chromane natural product isolated from Cassia fistula: 1-(3,4-dihydro-5-meth- oxy-2,2-dimethyl-2H-chromen-7-yl)propan-2-one. The preparatory route of this natural product features two synthetic methods developed by the Magolan group, including the aldehyde to ketone homologation described in Chapter 2. The five-step total synthesis affords the natural product in 24% overall yield and includes an efficient one-pot three-transformation sequence. Chapter 5 highlights ongoing and future projects that build on the research described in this thesis. This includes investigations into stable intermediates that facilitate access to aldehydes from vinyl sulfides. Plans are proposed to develop controlled stereoselective use of thiophosphonium reagents. Further collaborative work is discussed employing vinyl sulfides as substrates for valuable atropoisomeric heterocyclic scaffolds. / Thesis / Doctor of Philosophy (PhD)

Thesis advisor: Jason S. Kingsbury / The research of diazoalkanes dates back more than 100 years, yet a disproportionally small number of methods have been developed to utilize their unique reactivity patterns. This review seeks to analyze the history of methods used to synthesize diazoalkanes and to highlight the parallel growth in methods for their use in carbonyl expansion reactions. The development of Sc(III)-catalyzed ring expansion of cyclic ketones with non-stabilized diazoalkanes is presented. A brief overview of previous contributions to ring expansion methodology is presented in order to provide appropriate context to newly discovered methods. Our strategy for method development centered on several issues of practicality with regard to efficient synthesis of diazo nucleophiles as well as their safe handling. The results of this initial discovery laid the groundwork for the development of the first catalytic enantioselective ring expansion of cyclic ketones with diazoalkanes. As well as an improved methylene insertion reaction of silyl-substituted diazomethanes. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Hormis la préparation de l’acide salicylique et de l’urée, peu de tentatives ont été réalisées jusqu’à présent pour promouvoir la formation de liaisons C–C et C–N à partir du CO₂. Cette thèse présente de nouveaux procédés catalytiques permettant la formation de molécules organiques azotées grâce à la création de liaisons C–N et C–C par transformation catalytique du CO et du CO₂. Les cibles retenues sont les amides ainsi que les alkylamines qui sont essentiels en chimie organique fine et sont souvent d’origine pétrosourcés. Dans un premier temps, la synthèse d’amide par carbonylation formelle de la liaison C–N d'amine sera étudiée grâce à des catalyseurs à base de métaux carbonyles. Dans un second temps, des procédés d’homologation des amines seront décrits grâce à l’utilisation de catalyseurs métalliques. La première stratégie impliquera l’utilisation de catalyseur de cobalt, en présence de CO et de silanes et permettra l’homologation sélective des liaisons N-méthyle en N-éthyle sous de faible pression de CO (P = 8 bar) et jusqu’au N-pentyle sous de fortes pressions. Dans un second temps, l’utilisation d’un catalyseur de ruthénium en présence d’un gaz de synthèse (CO/H₂) nous permettra de démontrer la possibilité de l’homologation de la diphénylamine. Enfin, la compréhension de ce système nous permettra de transposer cette réaction à l’utilisation du CO₂ comme substitut du CO. / Apart from the preparation of salicylic acid and urea, few attempts have been made so far to promote the formation of C-C and C-N bonds from CO₂. This thesis describes new catalytic processes allowing the formation of nitrogen compounds through the creation of C-N and C-C bonds by catalytic transformations of CO and CO₂. The chosen targets are the amides and the alkylamines which are essential in fine organic chemistry and yet prepared from petrochemicals. In a first part, the amide synthesis by formal carbonylation of the C-N bond HAS been studied using catalysts based on first row transition metal carbonyl complexes. In a second part, methods enabling homologation of amines are described through the use of metal catalysts. The first strategy involved the use of cobalt catalysts in presence of CO and hydrosilanes which allow the selective homologation of N-methyl into N-ethyl derivatives under a low CO pressure (P= 8 bar). Also, the alkyl chain can be homologated under elevated CO pressures to reach N-pentyl derivatives. Finally, the use of a ruthenium catalyst in presence of a synthesis gas (CO / H₂) allowed us to demonstrate the possibility of the homologation of the diphenylamine. Understanding this system led to translate the amine homologation with syngas to the use of CO₂ as a substitute for CO.

Lorsquil recourt à la technique de lhomologation en matière contractuelle, le législateur permet ou impose aux parties quaucun litige noppose (plus), de soumettre leur convention au contrôle dun juge. Bien que la décision que le juge rend à lissue de ce contrôle soit susceptible de modifier le rapport contractuel de base, le législateur na pas défini le régime et les effets de lhomologation. Lauteur tente de mettre au jour le corps des règles communes aux différentes homologations de contrats et de préciser, eu égard à ces règles, lincidence de lintervention judiciaire sur les relations des parties entre elles et vis-à-vis des tiers. Dans la première partie de létude, est développé le contexte dans lequel sinscrit lhomologation judiciaire des conventions. Cette partie est axée sur les deux aspects que comporte ce contexte; le premier titre est consacré au rôle du juge face au litige et le second au rôle du juge face au contrat. La seconde partie de létude contient les développements propres à la théorie de lhomologation judiciaire des conventions. Pour construire cette théorie, lauteur est amené à conjuguer la nature contractuelle de la convention soumise à homologation et la nature judiciaire de cette dernière. En définitive, il sagit de répondre à la question qui sous-tend le concept : lhomologation transmue-t-elle la convention qui lui est soumise ? Par lélaboration de la théorie générale, lauteur a cherché à faciliter la tâche des magistrats appelés, dans nombre dhypothèses, à homologuer des conventions, comme à éclairer les praticiens, sur les effets de lhomologation judiciaire des conventions.

La 20(S)-camptothécine (CPT) est un alcaloïde pentacyclique doté d'une activité anticancéreuse remarquable, agissant comme inhibiteur de la topoisomérase I (topo I). Le problème majeur de ce composé (et de la plupart de ses dérivés) est la fragilité de son cycle E qui s'hydrolyse rapidement à pH physiologique pour conduire au carboxylate correspondant inactif. L'une des approches permettant de pallier ce problème d'hydrolyse consiste à modifier le cycle E. Ce travail de thèse porte sur la synthèse totale de deux nouveaux analogues de la CPT modifiés au niveau du cycle E. Chacune de ces synthèses fait appel à une cycloaddition [3+2] afin de préparer l'hydroxypyridone de départ (cycles C et D), à un réarrangement de Claisen permettant de mettre en place le cycle E et à une condensation de Friedländer pour installer le motif quinoléinique (cycles A et B). Le premier analogue synthétisé, la (±) 17 norcamptothécine (17-norCPT), possède une α-hydroxy γ-lactone à la place de l'α-hydroxy δ-lactone de la CPT. Ce composé a été obtenu en neuf étapes avec un rendement de 4,4% à partir de l'hydroxypyridone de départ. Le test d'inhibition de la topo I a été réalisé, mais cette molécule s'est révélée totalement inactive. Cependant, une étude de la cinétique d'hydrolyse de la 17-norCPT, réalisée par spectroscopie de fluorescence, a permis de montrer que cet analogue était très instable en milieu aqueux. Le second composé préparé est en fait un homologue de la 17 norCPT possédant un méthylène entre l'oxygène et le carbonyle de la lactone. Cette molécule, comportant un motif céto éther, est donc un isomère de la CPT. Elle a été obtenue par deux voies de synthèse différant l'une de l'autre par l'ordre des réactions mises en œuvre. Chacune de ces approches permet d'obtenir le composé souhaité en neuf étapes à partir de l'hydroxypyridone de départ, avec un rendement de 16% et 10% respectivement. Les tests biologiques sur le composé final sont actuellement en cours. / 20(S)-Camptothecin (CPT) is a pentacyclic alkaloid endowed with remarkable anticancer activity, acting as an inhibitor of topoisomerase I (topo I). The major problem with this compound (and many of its derivatives) is the fragility of its E-ring, which suffers rapid hydrolysis at physiological pH to yield the inactive corresponding carboxylate. One of the approaches to overcome this problem of hydrolysis consists in modifying the E-ring. This thesis focuses on the total synthesis of two new E-ring modified CPT analogs. Each of the syntheses involves a [3+2] cycloaddition to prepare the starting hydroxypyridone (rings C and D), a Claisen rearrangement to realize the E-ring, and a Friedländer condensation to install the quinoline system (rings A and B). The first analog synthesized, (±) 17 norcamptothecin (17-norCPT), has an α-hydroxy γ-lactone in place of the α-hydroxy δ-lactone of CPT. This compound has been obtained in nine steps with a yield of 4.4% from the starting hydroxypyridone. Unfortunately, though, this molecule has proved to be totally inactive in the topo I assay. A kinetic hydrolysis study of 17-norCPT, carried out by fluorescence spectroscopy, has demonstrated, however, that this analog is, in fact, unstable in aqueous media. The second compound prepared is a homolog of 17-norCPT with a methylene between the lactone oxygen and carbonyl, thus a CPT keto ether isomer. It has been obtained through two synthetic routes that differ from each other in the order of the steps. Each of the approaches yields the desired compound in nine steps from the starting hydroxypyridone, with yields of 16% and 10% for the two syntheses. Biological tests on the final compound are currently underway.

No description available.

La thèse met en évidence, dans le cas de la France, une forme de régulation composite des risques sanitaires et environnementaux liés aux usages des pesticides par les jardiniers amateurs, qui comporte trois principales dimensions. (1) Intimement articulée aux mécanismes de marché, cette forme de régulation impute l'essentiel de la responsabilité à l'utilisateur considéré en tant que consommateur à responsabiliser, alors que les autorités publiques considèrent les firmes de pesticides comme des opérateurs économiques dont les avantages compétitifs sont à valoriser, veillant donc à respecter la dynamique de l'offre et de la demande tout en se chargeant d'encadrer ce marché par l'homologation des produits. (2) Elle épouse les principes de la société singulariste où l'individu serait la référence centrale de la dynamique des sociétés contemporaines et le régulateur des problèmes collectifs par ses choix de consommation et ses prises de positions individuelles. (3) Elle s'opère dans un contexte où l'État a per¬du sa centralité sous la double influence de l'européanisation et de la décentralisation et où les modes de régulations politiques sont caractérisés par des formes moins dirigistes de gouvernement pouvant être définies comme des " politiques sans politique ". La régulation composite des pesticides domestiques est porteuse d'un postulat implicite qui impute la responsabilité des risques aux usagers et qui, si elle laisse ouverte la voie à une po¬ten-tielle réduction de l'usage des produits, tend à limiter leur exclusion et réduit les possibilités d'une transition vers un jardinage sans pesticides.

La thèse met en évidence, dans le cas de la France, une forme de régulation composite des risques sanitaires et environnementaux liés aux usages des pesticides par les jardiniers amateurs, qui comporte trois principales dimensions. (1) Intimement articulée aux mécanismes de marché, cette forme de régulation impute l’essentiel de la responsabilité à l’utilisateur considéré en tant que consommateur à responsabiliser, alors que les autorités publiques considèrent les firmes de pesticides comme des opérateurs économiques dont les avantages compétitifs sont à valoriser, veillant donc à respecter la dynamique de l’offre et de la demande tout en se chargeant d’encadrer ce marché par l’homologation des produits. (2) Elle épouse les principes de la société singulariste où l’individu serait la référence centrale de la dynamique des sociétés contemporaines et le régulateur des problèmes collectifs par ses choix de consommation et ses prises de positions individuelles. (3) Elle s’opère dans un contexte où l’État a per¬du sa centralité sous la double influence de l’européanisation et de la décentralisation et où les modes de régulations politiques sont caractérisés par des formes moins dirigistes de gouvernement pouvant être définies comme des « politiques sans politique ». La régulation composite des pesticides domestiques est porteuse d’un postulat implicite qui impute la responsabilité des risques aux usagers et qui, si elle laisse ouverte la voie à une po¬ten-tielle réduction de l’usage des produits, tend à limiter leur exclusion et réduit les possibilités d’une transition vers un jardinage sans pesticides. / In 2008, the amount of pesticides used by amateur gardeners in the approximately fifteen million private gardens which exist in France and which represent a total area of a million hectares, rose to 3500 tons. Within the framework of a highly growing social awareness regarding health and environment problems and whilst the cut back on the use of pesticides in agriculture represents one of the main political objectives in the field of environmental protection, and Europe defines its chemical substances control policies (REACH), a study on the use of pesticides in gardening practices represents a good observation point to understand representations, dispositions and social practices linked to the use of pesticides in private gardens, to question the announced “greening” of life styles, to appreciate the capacity of the commercial production-distribution chain to manage such problems, and finally to evaluate the impact and direction of public policies to prevent health and environment risks.The results of the thesis are supported by sociological investigations carried out with amateur gardeners, by means of questionnaires (N=900) and interviews (N=24), with producers and distributors of phytosanitary products and with the press specialized in gardening (N=17) in France. The analysis of the pesticides code of management applied since 2003 in Quebec and which constitutes a regulation which prohibits the use and sale of a series of pesticides recognized as the most hazardous health-wise in municipal and private gardens, represents a counterpoint of the French situation.In the case of France, the thesis underlines a sort of composite regulation regarding the sanitary and environmental risks linked to the use of pesticides by amateur gardeners, involving three dimensions. (1) Intimately linked to the marketing mechanisms, this type of regulation attributes the core of the responsibility to the user, considered as the consumer to be blamed, while public authorities consider the firms which produce the pesticides as economic operators whose competitive advantages must be considered, seeking to respect the dynamics of offer and demand as well as controlling this market based on product certification. (2) It adopts the principles of the one-man society where the individual would be the main reference of the dynamics of contemporary societies and the regulator of collective problems based on his consumer choices and his individual position-taking. (3) It is located in a context where the State has lost its central position under the double influence of “Europeanization” and “decentralization” and where the types of political regulations are characterized by less interventionist forms of government, which can be defined as “politics without politics”. The composite regulation of domestic pesticides has an implicit postulate which attributes the responsibility of the risks involved to the users and which , in case of leaving an open door to the potential reduction of the use of products, tends to limit their exclusion as well as the possibilities of a transition towards pesticide free gardening.

Background: South Korea is one of the countries currently enforcing more strict emission standards for heavy-duty vehicles, as a result of the global push to restrict pollution. In addition, there has been recent scandals involving several well-established automotive companies manipulating emissions tests and not fulfilling regulations. This has resulted in the government increasing the pressure for companies to apply the correct certifications even further. For companies to sell vehicles on the South Korean market, the vehicles must be certified and approved by the government, known as homologation. This process partly involves self-certification, meaning that companies are responsible for applying the correct certification themselves. It is therefore of great importance to have structured and clear processes to mitigate risks of error-making, in order to avoid financial and legal repercussions. Purpose: The study aims to identify and analyze the risks in error-making. Therefore, the purpose is to understand and propose improvement actions to the current homologation processes at Scania Korea Group. Method: The thesis utilized a case study strategy with a descriptive approach to illustrate the process. An exploratory approach was used in combination to identify risks and provide improvement actions. Qualitative data in conjunction with theory around business process improvement were utilized to fulfill the purpose. Firstly, interviews and focus groups were conducted to map the process. Thereafter, a failure mode and effect criticality analysis(FMECA) was used to analyze the process. Lastly, improvement actions were decided based on best practices and benchmarking. Findings and recommendations: The homologation process contain many high severity risks such as certifying the incorrect truck specifications or not complying with regulations, due to not updating the certifications when product changes occur. Furthermore, government approvals incorporate a substantial part of the process lead-time. As such, it is concluded that quality is of utmost importance, both to decrease lead-time and minimize risks with detrimental consequences. The analysis showed evidence of lacking controls/gates in the process, which enables errors and incorrect applications to move through. Improvements regarding increased project structure, planning and communication within SKG were suggested. Further improvement points were an increased number of controls and more clear delegation of responsibility. Recommendations for future studies: We propose to further investigate the root-causes of the inherent risks in the process. Future studies should also look to gather additional data from other heavy-duty automotive companies in South Korea, since it could provide deeper and more generalizable results. Lastly, we recommend future research to utilize a quantitative research approach, providing more statistical evidence.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-01-11T15:47:20Z No. of bitstreams: 1 Sílvia Regina Zomer.pdf: 1000604 bytes, checksum: f2871208a979b94113d5568e7717839c (MD5) / Made available in DSpace on 2017-01-11T15:47:20Z (GMT). No. of bitstreams: 1 Sílvia Regina Zomer.pdf: 1000604 bytes, checksum: f2871208a979b94113d5568e7717839c (MD5) Previous issue date: 2016-12-15 / This doctoral thesis aims to analyze time as an instituting element of the juridical reality, specifically, in the conformation of the tacit homologation. We delimit the context that circumscribes the field of investigation of this work to the positive law, considering it, a priori, as a communicational phenomenon capable of regulating intersubjective behaviors from the set of valid legal norms, conveyed by prescriptive statements produced under certain conditions of space and time, which is why we seek to base the presuppositions systematized by the Philosophy of Language and in Logical-Semantic Constructivism, conceived as an appropriate approximation method to conduct the analysis of the prescriptive language of law, in its syntactic, semantic and pragmatic aspects, attempting to demonstrate, conclusively, that the tacit approval is only lapse juridical fact, instituted according to art. 150, § 4 of the National Tax Code / Esta tese de doutoramento tem por objetivo analisar o tempo como elemento instituinte da realidade jurídica, especificamente, na conformação da homologação tácita. Delimita-se o contexto que circunscreve o campo investigativo deste trabalho ao direito positivo considerando-o, a priori, como um fenômeno comunicacional capaz de regular condutas intersubjetivas a partir do conjunto de normas jurídicas válidas, veiculadas por enunciados prescritivos produzidos sob determinadas condições de espaço e tempo, razão pela qual, busca-se fundamentos nos pressupostos sistematizados pela Filosofia da Linguagem e no Construtivismo Lógico-Semântico, concebido este como um método de aproximação apropriado para conduzir a análise da linguagem prescritiva do direito, nos seus aspectos sintático, semântico e pragmático, na tentativa de demonstrar, ao final, tratar-se a homologação tácita, apenas, de fato jurídico decadencial, instituído conforme o art. 150, § 4º do Código Tributário Nacional