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Chiral amines are widespread in naturally occurring and synthetic bioactive molecules. However, it remains challenging to synthesise these molecules in an enantiopure form. Investigations within our group have shown that treatment of vinylic ureas with organolithium reagents results in an umpolung addition of the organolithium, followed by N to C aryl migration of the lithiated intermediate. This thesis details investigations into developing an enantioselective version of this reaction through the use of the chiral ligands (−)-sparteine and the (+)-sparteine surrogate. The enantioenriched ureas are easily transformed into the corresponding a-tertiary amines. Use of the different chiral ligands allows access to either enantiomer of the rearranged urea. Further work has centred on the application of this methodology towards cyclic substrates; with a view to synthesising a-tertiary cyclic diaryl amines. Studies have shown that treatment of vinylic ureas bearing cyclic substituents with a number of different organolithium reagents successfully produce the desired rearranged ureas, with complete diastereoselectivity. Subsequent solvolysis of these ureas yields hindered cyclic a-tertiary amines in good yields. During these investigations it has been shown that allylic ureas undergo a rearrangement to the least sterically hindered side of the cyclic urea. This allows for fine tuning of the migration reaction depending on where the double bond is positioned in the molecule. A range of vinylic and allylic ureas, including substrates with interesting pharmaceutical properties, have been investigated. Their synthesis and reactivities upon lithiation are discussed within this thesis.

Directed metalation reactions are an interesting area of synthetic chemistry. They provide a powerful regiospecific method for functionalizing complex aromatic rings. Presently, directed ortho metalations are well understood. However, there has been very little progress in the remote metalation of naphthalene derivatives. Presently the peri lithiation of naphthalamides is a reaction that has not been solved to a level that allows for it to be deployed in a vast number of synthetic schemes. The processes by which peri functionalized naphthalamides are present obtained required several steps and give poor yields. Previously attempts directed toward the peri lithiation in the Schwan lab have met with little success. Herein experiments were preformed to understand why the pervious attempts failed and other experiments were performed in an effort to acheive the peri lithiation of a specific naphthalamide. The mechanism of previous chemical observations was understood by trapping experiments and clearly demonstrated how problematic acidic sites can interfere with intended directed metalation. The acidic site was sterically hindered by employing strategic protecting groups. However, the steric demand of the protecting groups considered was not sufficient to eliminate the problematic acidic site. This led to the consideration of an alternative strategy for the peri lithiation by removing the acidic center of the specific substrate. This however, resulted in remote addition of lithiating reagents to the naphthalamide and clearly showed that several naphthalamides are not a suitable directed metalation group for the peri lithiation.

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Nowadays, Lithium-ion batteries (LIBs) have dominated the power source market in a variety of applications. Lithium cobalt oxide (LiCoO2) is one of the most common cathode materials for LIBs in consumer electronics. The recycling of LIBs is important because cobalt is an expensive element that is dependent on foreign sources for production. Lithium-ion batteries need to be recycled and disposed properly when they reach the end of life (EOL) to avoid negative environmental impact. This project focuses on recycling cathode material (LiCoO2) by direct method. Two automation stages, tape peeling stage and unrolling stage, are designed for disassembling prismatic winding cores. Different sintering conditions (e.g., temperature, sintering atmosphere, the amount of lithium addition) are investigated to recycle EOL cathode materials. The results show that the capacity of the recycled cathode materials increases with increasing temperature. The extra Li addition leads to worse cycling performance. In addition, the sintering atmosphere has little influence on small- scale sintering. Also, most of directly recycled cathode materials have better electrochemical (EC) performance than commercial LiCoO2 (LCO) from Sigma, especially when cycling with 4.45V cutoff voltage. / Master of Science / Nowadays, Lithium-ion batteries (LIBs) have dominated the power source market in a variety of applications. A LIB contains an anode, a cathode and electrolyte. The cathode material is the most valuable component in the LIB. Lithium cobalt oxide (LiCoO2) is one of the most common cathode materials for LIBs in consumer electronics. The recycling of LIBs is important because cobalt is an expensive element that is dependent on foreign sources for production. Lithium-ion batteries need to be recycled and disposed properly when they reach end of life (EOL) to avoid negative environmental impact. The direct recycling is a cost effective and energy conservative method which can be divided into two steps: retrieving the cathode materials from EOL LIBs and regenerating the cathode materials. This project focuses on recycling LiCoO2 by direct method. Two automation modules, tape peeling stage and unrolling stage, are designed for a disassembling line which is the automation line to collect the cathodes materials. The EOL cathode materials is lithium deficient (Li1-xCoO2). To regenerate the EOL cathode materials, lithium is added into structure of cathode materials which is called the re-lithiation process. The different sintering conditions (e.g., temperature, sintering atmosphere, the amount of lithium addition) are investigated for the re-lithiation process. The results show that the capacity of the recycled cathode materials increases with increasing temperature. The extra Li addition in iv Li1-xCoO2 leads to worse cycling performance. In addition, sintering atmosphere has little influence on small- scale sintering. Most of directly recycled cathode materials have better electrochemical (EC) performance than commercial LiCoO2, especially when cycling with 4.45V cutoff voltage.

Nous avons développé une procédure simple et originale pour la synthèse de dérivés 4,4'-bipyridines polyhalogénées basée sur la lithiation de dihalogénopyridines. Le mécanisme de cette réaction a été étudié par l'isolement et la caractérisation de plusieurs produits secondaires. La méthodologie adoptée a été ensuite appliquée à la synthèse d'une série de bipyridines 4,4' comportant des atomes de chlore, de brome et aussi d'iode. Dans certains cas, nous avons pu isoler des bipyridines ayant une connectivité 3,4' et 2,4'. Quelques 4,4'-bipyridines ont été fonctionnalisées par couplages croisés de Suzuki et par double amination de Buchwald-Hartwig. La plupart des produits ont été caractérisés par diffraction des rayons X ce qui a montré des interactions halogènes spécifiques / We have developed a simple and original procedure for the synthesis of halogenated 4,4'-bipyridines based on the lithiation of halopyridines. The mechanism of the reaction has been studied by isolation and characterization of several byproducts. The methodology was then applied to the formation of several 4,4'-bipyridines bearing chlorine, bromine, and even iodine. In some cases we could isolate bipyridines having 3,4' and 2,4' connectivity. Some 4,4'-bipyridine have been functionalized by Suzuki cross-coupling and Buchwald-Hartwig double amination. Most representative products were characterized by X-ray diffraction and showed specific halogen interactions

Afin de corriger la suractivation de la voie de signalisation Raf/MEK/ERK observée dans 30 % des cancers,nous avons choisi d'inhiber la kinase Raf-1. Les inhibiteurs potentiels de Raf-1 ont été conçus avec un cyclecentral original 4-azaindolique. Pour apporter de la diversité fonctionnelle au niveau des sommets C-2 et C-5lors de la synthèse, nous avons optimisé deux méthodes à partir du synthon 5-méthoxy-4-azaindole-Nphénylsulfonyle.La première est une réaction de lithiation du sommet C-2 suivie de la condensation dedifférents électrophiles et la deuxième est la C-arylation ou N-arylation du sommet C-5 à partir du dérivétriflate en 5 via des réactions de couplage pallado-catalysées de type Suzuki et Buchwald, respectivement.Ces deux méthodes ont permis d'aboutir à 2 séries de composés : une première série fonctionnalisée enposition N-1 et C-5 du noyau 4-azaindole et une deuxième série substituée en position C-5 et C-2.Pour tester les nouveaux inhibiteurs synthétisés et un inhibiteur naturel appelé PEBP, nous avons mis aupoint des tests d'activité in vitro sur l'ensemble de la cascade Raf/MEK/ERK et sur chacune des 3 kinases.Les tests ont été développés avec 2 méthodes de TR-FRET, Lance UltraTM et LanthascreenTM, et ont étévalidés avec des inhibiteurs commerciaux et comparés par rapport à la méthode radioactive PFBA.Au total, 30 produits finaux ont été évalués in vitro sur la kinase Raf-1. Grâce aux plateformes duCancéropôle GO, les produits ont aussi été testés sur 6 lignées de cellules cancéreuses et sur les kinasesdu cycle cellulaire DYRK1A, GSK3 et CDK5. Plusieurs molécules ont montré une activité antitumoraleencourageante de l'ordre du μM et un composé a été identifié comme inhibiteur de Raf-1 avec une valeurd'IC50 de 9,8 μM et une cytotoxicité sélective vis-à-vis des cellules du foie Huh7 (IC50 = 3 μM).