This thesis presents the application and development of H-bond donor organocatalysts. Chapter 2 presents an intramolecular Michael addition of β-dicarbonyls onto α,β-unsaturated esters catalyzed by tertiary amine/H-bond donor bifunctional catalysts, achieving up to 88% ee. Chapter 3 outlines the design and synthesis of a new family of cinchona-derived H-bond donor/ammonium salt phase-transfer catalysts. The ability of these asymmetric phase-transfer catalysts to activate less reactive substrates than their tertiary amine analogues and to induce higher levels of enantiocontrol than commercially available phase-transfer catalysts was demonstrated in an intramolecular Michael addition. Chapter 4 details the highly successful application of these new H-bond donor/ammonium salt phase-transfer catalysts to the enantio- and diastereoselective nitro-Mannich reaction of α-amido sulfones with nitroalkanes. Preliminary investigations into a novel phase-transfer catalyzed asymmetric ketimine reduction demonstrate the ability of these catalysts to provide access to new methods.

Hydroamination reactions are very attractive to form new C-N bonds, though broadly applicable synthetic methods do not exist. The hydroamination of unactivated alkenes is especially difficult to accomplish given its negative reaction entropy, as well as potentially being a thermodynamically unfavourable transformation with some substrates. Thus, previously reported systems have often consisted of biased intramolecular systems or metal-catalyzed intermolecular variations operating at low temperatures. Recently, our group discovered that intermolecular Cope-type hydroamination of unactivated alkenes is achievable through the use of aldehydes as catalysts. These organocatalysts act solely through promoting the pre-association of reacting partners, hydroxylamines and allyl amines, in order to induce temporary intramolecularity; thus allowing for very mild reaction conditions and access to important 1,2-Diamine motifs. This thesis presents studies expanding upon initial reports of aldehyde-catalyzed Cope-type intermolecular hydroamination. In the scope of these studies standard conditions were developed to compare aldehyde catalytic activity. These evaluations led to further strengthening our understanding of hypothesized trends in aldehydes’ catalytic efficiencies, notably the impact of electronic, steric and solvent effects. Furthermore, the possibility of using a catalytic precursor species for hydroamination was evaluated. While this symmetrical hydroxylamine dimer precursor did not result in increased hydroamination yields, it did allow for easier manipulations as well as allow preliminary kinetic isotope effect studies to study formaldehyde as a precatalyst. These KIE studies allowed to reconfirm that hydroamination was highly likely the rate determining step of our proposed catalytic cycle. Derivatization of hydroamination products was also accomplished to access important 1,2 Diamine motifs from simple starting materials, also allowing to access difficult hydroamination products through the application of quantitative amounts of aldehyde, followed by hydrolysis of the formed heterocycles. Additional studies into nitrone reactivity led us to access a novel synthesis of enantiomerically enriched chiral cyclic nitrones through a sequence of nucleophilic addition, Cope-type hydroamination and Cope elimination. However, this sequence proved unpractical and of very narrow applicability, while affording only modest enantioselectivities (up to 78% ee), therefore further exploration was not warranted. A collaborative study was also undertaken in collaboration with the Wennemers group from ETH Zurich. This exploratory study had the goal of examining the potential for combining small peptide catalysis with aldehyde catalysis inducing temporary intramolecularity. It was hypothesized that the combination of both catalytic systems could improve upon the conjugate addition of nucleophiles to certain electrophiles, such as nitroolefins; in a potentially stereoselective manner. Although initial trials did not yield productive reactions, evidence for potential new mixed aminals with formaldehyde and various nucleophiles was found. Furthermore, the background reactivity of various nucleophile and electrophile pairings was assessed, allowing for better calibration of future efforts in studying such systems.

Ce manuscrit traite de la synthèse d'aldols mono- et difluorés à partir de précurseurs stables d'éthers d'énol silylés. En premier lieu, la synthèse et la réactivité de synthons de type RCF2Li sont abordées. Cette étude a notamment permis d'obtenir des alpha-trialkylsilylcarbinols stables par addition sur des acylsilanes. Ces composés nous sont apparus comme des précurseurs stables de fluoroénolates, capables de générer in situ ces nucléophiles après réarrangement de Brook et élimination d'un fluorure sous l'action d'une base. La deuxième partie de ce manuscrit traitera ainsi de deux méthodologies monotopes permettant d'aboutir à des aldols monofluorés comportant un centre tétrasubstitué fluoré directement à partir de ces précurseurs: soit en utilisant un équivalent de t-BuOK, soit avec une quantité catalytique de p-MeOPhONBu4 en présence d'une base relais. Dans un troisième temps, en se basant sur une séquence similaire, une synthèse monotope racémique d'aldols difluorés à partir du réactif de Ruppert-Prakash, d'acylsilanes et d'aldéhydes a été mise au point. Cette réaction étant catalysée par le TBAT, une version asymétrique organocatalysée a ensuite été explorée grâce à l'utilisation de paires d'ions chiraux coopératifs. / This manuscript deals with the synthesis of mono- and difluorinated aldols starting from stables precursors of silylated enol ethers. First, the synthesis and the reactivity of RCF2Li synthons has been investigated. A preparation of alpha-trialkylsilylcarbinols, which can be seen as fluoroenoxysilane precursors, has been developed. A sequence involving a Brook rearrangement followed by a fluoride elimination from these stable precursors has then been exploited in a second part to set up a one-pot preparation of monofluorinated aldols featuring a fluorinated tetrasubstituted center. Two methodologies were developped : one relying on the addition of a stoichiometric amount of t-BuOK and the second involving a catalytic amount of p-MeOPhONBu4 and a stoichiometric amount of a pro-base. Finally, a one-pot synthesis of difluorinated aldols starting from Ruppert-Prakash reagent, acylsilanes and aldehydes is described in a third part. This sequence, similar to the previous one, is catalyzed by TBAT and an asymmetric version relying on the use of chiral cooperative ion pairs has also been explored.

Les dérivés ambiphiles, possèdant un site acide de Lewis (B ou Al) et un site base de Lewis (P), sont connues pour activer les petites molécules, stabiliser des espèces hautement réactives, mais aussi pour se comporter comme des catalyseurs non-métalliques. Dans la mesure où ils présentent différents modes de coordination, ils possèdent des comportements variables en tant que ligands des métaux de transition. Cette thèse porte sur deux aspects des composés ambiphiles. Le premier concerne l'interaction avec les petites molécules et l'organocatalyse, et le second la coordination et la réactivité des complexes métalliques avec des ligands ambiphiles. Le premier chapitre aborde la synthèse et la réactivité de phosphines-boranes possédant un espaceur de type ortho-phénylène. Dans une première partie, des composés possédant des sites base et acide de Lewis de nature différente ont été synthétisés. Dans une seconde partie, les propriétés catalytiques de ces dérivés ont été évaluées lors de la réduction du dioxyde de carbone en présence de boranes. Ces dérivés ambiphiles se sont révélés être des organocatalyseurs efficaces pour cette réaction. Dans une troisième partie, une étude mécanistique a été réalisée. Lors de cette étude, un intermédiaire réactionnel a pu être isolé et caractérisé. Cette espèce, possédant une molécule de formaldéhyde pontante entre les atomes de phosphore et de bore, s'est montrée plus efficace en catalyse que les catalyseurs précédents. En effet, aucune période d'induction n'est observée lors de la réduction du dioxyde de carbone avec ce dernier. Le second chapitre aborde la réactivité d'un complexe de Pt possédant un ligand ambiphile de type phosphine-alane (PAl). Ce complexe comportant une interaction Pt-->Al, avait déjà montré une réactivité intéressante vis-à-vis de l'hydrogène. Dans ce chapitre, sa réactivité vis-à-vis d'autres substrats a été étudiée. Dans une première partie, la capacité du complexe PAl-Pt à activer une liaison N-H polaire a, en particulier, été évaluée. Un complexe issu de l'addition oxydante de PhC(O)NH2 sur le platine a pu être isolé et entièrement caractérisé. Dans une seconde partie, le complexe PAl-Pt a été mis en présence de petites molécules de type CE2 (E = O, S) et différents modes de coordination ont pu être mis en évidence aussi bien en solution et qu'à l'état solide. En particulier, un complexe n1 de CO2 a été isolé. Au cours de ce travail, l'accent a été mis sur la coopérativité d'action métal/acide de Lewis. / Ambiphilic derivatives, which possess a Lewis acid (B or Al) and a Lewis base (P), are known for activating small molecules, stabilizing highly reactive species, but also to be used as metal-free catalyst. Because of their different coordination modes, they show different behaviour as ligand for transition metals. This thesis addresses two aspects of ambiphilic derivatives. The first one is about the interaction with small molecules and the organocatalysis, and the second one the coordination and the reactivity of metallic complexes with ambiphilic ligands. The first chapter deals with the synthesis and the reactivity of phosphine-borane which possess an ortho-phenylene backbone. In the first part, compounds with different kind of Lewis base and acid have been synthesized. In a second part, catalytic properties of these derivatives have been evaluated for the reduction of carbon dioxide in presence of borane. These ambiphilic derivatives have revealed themselves as effective organocatalyst for this reaction. In a third part, a mechanistic study have been realised. During this study, a reaction intermediate has been isolated and characterized. This species, which possess a molecule of formaldehyde bridging between the atoms of phosphorus and boron, revealed itself more effective in catalysis that the previous catalyst. Indeed, no induction period has been observed during the reduction of carbon dioxide with this compound. The second chapter relates the reactivity of a Pt complex which possess a phosphine-alane (PAl) type ambiphilic ligand. This complex involving a Pt-->Al interaction, has already shown an interesting reactivity toward dihydrogene. In this chapter, his reactity toward other kind of substrate has been studied. In a first part, the capacity of the PAl-Pt complex to activate a polar N-H bond has been evaluated. A complex coming from the oxidative addition of PhC(O)NH2 over the platinum has been isolated and fully characterized. In a second part, the PAl-Pt complex has been set to react with CE2 (E = O or S) type small molecules, and different coordination modes have been highlighted both in solution and in solid state. In particular a n1 CO2 coordinated complex has been isolated. During this work, the cooperativity of action metal/Lewis acid has been emphases.

Développement de méthodes d'α,β-fonctionnalisation d'amines et formation d'hétérocycles optiquement actifs via l'utilisation de l'organocatalyse et de la catalyse photoredox. / Development of methods α,β-functionalization of amines andformation of optically active heterocycles via the use of the organocatalysis and thephotoredox catalysis.

Sur la base des travaux antérieurs du laboratoire, nous avons développé une nouvelle approche synthétique énantiosélective, en deux étapes, pour l’accès à des glutarimides fonctionnalisés à partir de cyclobutanones facilement accessibles, selon deux directions: une stratégie impliquant une extension de cycle à deux atomes et une stratégie basée sur une contraction de cycle à deux atomes. En parallèle, nous avons démontré que les arynes porteurs de la chiralité axiale en position ortho de la triple liaison réactive peuvent être générés à partir des précurseurs iodo/triflate de type Suzuki et réagissent in situ avec divers substrats. Leur stabilité configurationnelle et leur grande réactivité nous ont permis de proposer une nouvelle méthode de synthèse pour introduire un fragment biaryle à chiralité axiale au sein de pratiquement toutes molécules organiques réactives vis-à-vis des arynes / Based on the previous work in our laboratory, we have developed a new enantioselective two-step synthetic approach to access functionalized glutarimide derivatives using readily available cyclobutanones following two directions: a two-atom ring expansion strategy and a two-atom ring contraction strategy. Meanwhile, we have demonstrated that arynes bearing axial chirality ortho to their reactive triple bond can be generated from the corresponding iodo/triflate Suzuki-type precursors and trapped in situ by various substrates. Their configurational stability and high reactivity allow us to propose a new synthetic method for the facile introduction of an axially chiral biaryl unit onto virtually any organic molecule reacting with arynes

Se ha estudiado la actividad catalítica de materiales derivados de grafeno como soporte de nanopartículas de paladio así como de complejos de paladio(II) en reacciones de acoplamiento carbono-carbono y carbono-heteroátomo. Así mismo, se ha llevado a cabo su actividad catalítica como carbocatalizador en diversas transformaciones orgánicas.

Pleiomaltinine is an alkaloid-pyrone natural product that was the first of its kind to be isolated in nature. Synthesis of this compound from pleiocarpamine and a reactive quinone methide-like pyrone is described. Furthermore, model compounds have been made that will allow for full testing of this new heterocycle’s biological properties. This process has also been rendered enantioselective using asymmetric organocatalysis with thioureas. Additionally, work has been conducted towards the total synthesis of vinylallene-derived natural products. Progress towards the syntheses of chloropupukeananin, chloropestolide A, pestalofone C, iso-A82775c, and maldoxin isolated from Pestalotiopsis fici are described. All of these compounds are complex and possess biological activities including anti-cancer and anti-HIV. The strategies applied to develop a selective synthesis of reactive vinylallenes are discussed and plans designed to overcome this synthetic challenge are shown in detail. New methodologies are presented along with literature precedent in these areas of research.

Document incorrectly classified as a dissertation on title page (decision to classify as a thesis from NDSU Graduate School) / Organocatalysis is a field that has bloomed over the last decades. With the field’s promise of being able to mimic nature and afford products in a synergistic manner to traditional Lewis acid catalysis, several interesting discoveries have been made. Owing to the vastness of the field as it exists today, this document will focus on two main aspects; cinchona alkaloid (and derivatives) as used in common carbon-carbon bond forming reactions and kinetic resolution via 4-dimethyl aminopyridine-N-oxide derivative driven acylation. Kinetic resolution via organocatalysis has the potential to react one enantiomer of a racemic mixture without affecting the other. The highlight of this screening was an s factor of 9 which was produced using optimized conditions using a catalyst designated DMAPO-IV. There remains much to do in improving the system and elucidating the scope of this catalytic system this report details the efforts made thus far.

No description available.