Parmi tous les plastiques, les polyuréthanes (PUs) représentent la sixième classe de polymères la plus utilisée au monde. Ils sont synthétisés industriellement par réaction entre un diol et un diisocyanate, en présence d'un catalyseur métallique et d’un solvant organique.Néanmoins, cette synthèse présente d’importants problèmes environnementaux et de santé.Afin de s’affranchir de ces composés toxiques, les progrès dans ce domaine ont conduit à un certain nombre de procédés sans isocyanates. Néanmoins, ces procédés doivent faire face à de nombreux défis (propriétés physiques, masses molaires, réactions secondaires, etc.), afin de concurrencer les polyuréthanes classiques. Par conséquent, une partie de ce manuscrit est dédiée à une étude rationnelle de l'influence de catalyseurs organiques, tels que le TBDou P4, non seulement sur la cinétique de polymérisation de l’aminolyse de carbonates biscycliques,mais aussi sur la structure et les propriétés des PUs résultants. Par la suite, et afin de limiter l’utilisation de composés organiques volatiles, des dispersions aqueuses de polyuréthanes sans isocyanates ont été obtenues en adaptant : 1) le procédé acétone à l’aminolysis de carbonates bis-cycliques et 2) la polymérisation interfaciale à la polycondensation de dicarbonates linéaires avec des diamines. / Among all plastic materials, polyurethanes (PUs) represent the 6th most popularly usedpolymers in the World. They are industrially synthesized by the reaction between a diol and adiisocyanate, in the presence of a metal catalyst and an organic solvent. Nevertheless, thissynthesis presents important environmental and health problems. In order to replace thesetoxic compounds, advances in this field have led to a number of isocyanate-free processes.However, these processes have to face many challenges (physical properties, molarmasses, side reactions, etc.), in order to compete with conventional polyurethanes.Therefore, part of this manuscript is dedicated to a rational study of the influence oforganocatalysts, such as TBD or P4, not only on the polymerization kinetics of the aminolysisof bis-cyclic carbonates, but also on the structure and properties of the resulting PUs.Subsequently, and in order to limit the use of volatile organic compounds, aqueousdispersions of non-isocyanate PUs were obtained by adapting: 1) the acetone process to theaminolysis of bis-cyclic carbonates and 2) the interfacial polymerization to thepolycondensation of linear dicarbonates with diamines.

This PhD thesis is focused on the development of novel low-oxidation state main group catalysis for organic synthesis. More specifically, the major objective has been to explore and design non-toxic and effective catalysts based on the following isoelectronic species: nitreones [nitrogen(I)], carbones [carbon(0)], and silylones [silicon(0)]; the corresponding central nonmetal atom in these molecules is in the formal low-oxidation state ‘+I’ and ‘0’, respectively. These species have been calculated to be strong Lewis and Brønsted bases. In addition, compared with established base catalysts such as N-heterocyclic carbenes (NHCs), nitreones, carbones, and silylones formally possess an additional lone pair of electrons at the central atom. In turn, these species may be used in base catalysis or as ligands in metal catalysis, and in the context of frustrated Lewis pair (FLP) or dual catalysis. The Lewis basicity of these N(I), C(0), and Si(0) compounds has been assessed with 11B NMR analysis using a variety of boron Lewis acids. These boron binding data have been compared with results obtained using NHCs as a Lewis base. Nitreones –more specifically cyclopropen-imines– have been explored in base catalysis. These N(I) Lewis bases have been uncovered to catalytically activate a variety of silicon-based pro-nucleophiles for subsequent bond formation with carbonyl and imine derivatives as well as aziridines. Successfully used pro-nucleophiles include TMS–CN, TMS– CF3, TMS–N3, and TMS–Cl. The characteristic features of this unprecedented cyclopropenimine Lewis base catalysis include low catalyst loading, mild reaction conditions, and broad substrate scopes. Various “normal” imines have proved to be catalytically inactive under the same conditions. In a similar context, carbones and silylones have been used to develop novel catalytic umpolung reactions, which turned out to be too challenging at this stage. Importantly though, silylones have been shown to activate the B–H bond of suitable pro-nucleophiles. Finally, several carbone–metal complexes have been synthesized and characterized. These novel species may be used in Lewis acid or dual catalysis after appropriate activation of the corresponding metal site.

In recent years, N-hetereocyclic carbenes (NHCs) have received considerable attention as organocatalysts due to their unusual ability to induce a reversal of reactivity (Umpolung) in aldehydes. Indeed, NHCs unique properties have been applied to the efficient and metal-free synthesis of organic compounds that have proven elusive using traditional approaches.<p> My Masters research program has been focused on the use of NHCs as organocatalysts in ring expansion reactions and their applications to cascade reactions.<p> During my Masters studies, an NHC-catalyzed efficient ring expansion of 4-, 5-, and 6-membered oxacycloalkane-2-carboxaldehydes to generate the corresponding lactone derivatives was developed. This reaction provides access to a variety of lactones using readily available NHCs under mild conditions.<p> Then, the ring-expansion lactonization has been successfully extended to an efficient lactamization using azacycloalkane-carboxaldehydes, which could provide functionalized lactams in moderate yields under mild conditions.<p> In addition, intrigued by the possibility of effecting the Umpolung of electron-poor dienes using NHC catalysts, the ring-expansion lactonization was applied to an attempted Diels-Alder-ring expansion cascade reaction. Though no cascade reactions were observed, some very interesting results were obtained, and those results will guide future investigations in this area.

In recent years, N-hetereocyclic carbenes (NHCs) have received considerable attention as organocatalysts due to their unusual ability to induce a reversal of reactivity (Umpolung) in aldehydes. Indeed, NHCs unique properties have been applied to the efficient and metal-free synthesis of organic compounds that have proven elusive using traditional approaches.<p> My Masters research program has been focused on the use of NHCs as organocatalysts in ring expansion reactions and their applications to cascade reactions.<p> During my Masters studies, an NHC-catalyzed efficient ring expansion of 4-, 5-, and 6-membered oxacycloalkane-2-carboxaldehydes to generate the corresponding lactone derivatives was developed. This reaction provides access to a variety of lactones using readily available NHCs under mild conditions.<p> Then, the ring-expansion lactonization has been successfully extended to an efficient lactamization using azacycloalkane-carboxaldehydes, which could provide functionalized lactams in moderate yields under mild conditions.<p> In addition, intrigued by the possibility of effecting the Umpolung of electron-poor dienes using NHC catalysts, the ring-expansion lactonization was applied to an attempted Diels-Alder-ring expansion cascade reaction. Though no cascade reactions were observed, some very interesting results were obtained, and those results will guide future investigations in this area.

<p>Density Functional Theory is used in order to shed light on the reaction mechanisms and the origins of stereoselectivity in enantioselective organocatalytic reactions. The reactions investigated are the dipeptide-catalyzed aldol reaction, the cinchona thiourea-catalyzed nitroaldol reaction and the prolinol derivative-catalyzed hydrophosphination reaction. We can justify the stereoselectivity in the reactions from the energies arising from different interactions in the transition states. The major contributions to the energy differences are found to be hydrogen bond-type attractions and steric repulsions. This knowledge will be useful in the design of improved catalysts as well as general understanding of the basis of selection in other reactions</p>

Chiral molecules as with biological activity are plentiful in nature and the chemical literature; however they represent a smaller portion of the pharmaceutical drug market. As asymmetric methodologies grow more powerful, the tools are becoming available to synthesize chiral molecules in an enantioselective and efficient manner. Recent breakthroughs in our understanding of phosphoric acid now allow for Lewis acid catalysis via pairing with alkaline earth metals. Using alkaline earth metals with chiral phosphates is an emerging approach to asymmetric methodology, but already has an influential record. The development of new conditions for the phosphoric acid-catalyzed highly enantioselective ring-opening of meso-aziridines with a series of functionalized aromatic thiol nucleophiles is described in this thesis. This methodology utilizes commercially available aromatic thiols, a series of meso-aziridines, and a catalytic amount of VAPOL calcium phosphate to explore the substrate scope of this highly enantioselective reaction. Additionally, the development of new conditions for a catalytic asymmetric aza-Darzens aziridine synthesis mediated by a vaulted biphenanthrol (VAPOL) magnesium phosphate salt is described in this thesis. Using simple substrates, this methodology explores the scope and reactivity of a new magnesium catalyst for an aziridination reaction capable of building chirality and complexity simultaneously.

Self-assembly is an efficient method for generating large numbers of structurally diverse catalysts for screening. In this work, the method of self-assembly was explored in the construction of bifunctional catalysts, from a chiral aminophosphine, 2-formylphenylboronic acid, and a (thio)urea-containing diol. These catalysts were evaluated by their effect on the asymmetric aza-Morita-Baylis-Hillman reaction. In the second half of this thesis, the hydrogen bonding abilities of different dithiosquaramides were analyzed. As thioureas have been shown to be stronger hydrogen bond donors than ureas, it was hypothesized that dithiosquaramides may also follow a similar trend. Affinities of corresponding squaramides and dithiosquaramides to chloride, sulfate, and tosylate were compared, as well as their abilities to catalyze the Freidel-Crafts alkylation between indole and trans-β-nitrostyrene.

Self-assembly is an efficient method for generating large numbers of structurally diverse catalysts for screening. In this work, the method of self-assembly was explored in the construction of bifunctional catalysts, from a chiral aminophosphine, 2-formylphenylboronic acid, and a (thio)urea-containing diol. These catalysts were evaluated by their effect on the asymmetric aza-Morita-Baylis-Hillman reaction. In the second half of this thesis, the hydrogen bonding abilities of different dithiosquaramides were analyzed. As thioureas have been shown to be stronger hydrogen bond donors than ureas, it was hypothesized that dithiosquaramides may also follow a similar trend. Affinities of corresponding squaramides and dithiosquaramides to chloride, sulfate, and tosylate were compared, as well as their abilities to catalyze the Freidel-Crafts alkylation between indole and trans-β-nitrostyrene.

This thesis is concerned with the use of Lewis base organocatalysts for carboxyl and acyl transfer reactions. Chapter 1 introduces the ability of organic Lewis bases other than DMAP-type to promote a range of asymmetric O-, N- and C-acyl transfer processes. This chapter summarizes the developments in catalyst architectures and approaches to these processes that have been disclosed to date in this dynamic area of asymmetric organocatalysis. Chapter 2 introduces studies into the synthesis of pyrrolyl carbonates via cyclization of gamma-amino esters and ring closing metathesis (RCM) of N-allylamides. The ability of a range of Lewis bases to promote the regioselective O- to C-carboxyl transfer of pyrrolyl carbonates is also presented. Chapter 3 introduces isothiourea DHPB as an efficient Lewis base catalyst for the diastereoselective C-acylation of silyl ketene acetals with anhydrides or benzoyl fluoride, giving 3-acyl-3-aryl or 3-acyl-3-alkylfuranones in excellent yields and stereoselectivities (up to 99:1 dr). Chapter 4 introduces C(2)-aryl substituted DHPB derived-isothioureas as efficient Lewis base catalysts for the enantioselective C-acylation of silyl ketene acetals with propionic anhydride, giving 3-acyl-3-aryl or 3-acyl-3-alkylfuranones in good isolated yields and enantioselectivities (up to 98% ee). This chapter also demonstrates that these chiral isothioureas are required for high reactivity and asymmetry in related acylation manifolds. Chapter 5 presents and overall conclusion for chapters 2,3 and 4. Chapter 6 contains full experimental procedures and characterization data for all compounds synthesized in Chapters 2, 3 and 4.

The research described in this thesis focuses on the catalytic acylative kinetic resolution (KR) of aromatic secondary alcohols, using a planar-chiral 4-(dimethylamino)pyridine (DMAP) organocatalyst. In the first part of this thesis, the substrate scope of the above mentioned process was expanded to aromatic secondary alcohols that contain an extra functional group in the alkyl moiety, such as 1,2-azido alcohols, 2-hydroxy-2-aryl-ethylphosphonates and 2-hydroxy-2-aryl esters. Thus, the preparation of highly functionalized compounds in their enantiomerically pure form with excellent enantiomeric excess (up to 99% ee) was achieved. Furthermore, the synthetic applicability of this methodology was illustrated through the synthesis of two high value compounds, (R)-Pronethalol and (S)-3-hydroxy-N-methyl-3-phenylpropanamide, which is an immediate precursor of bioactive molecules such as (S)-Fluoxetine. The second part of this thesis deals with the mechanistic study of the acylative KR catalyzed by the planar-chiral DMAP derivative. Reaction Progress Kinetic Analysis methodology was used in the investigation of the reaction mechanism, probing that no notable product inhibition or decomposition of the catalyst occurs in the studied system. The reaction rate showed fractional order dependence on the concentration of both reactants. Furthermore, NMR spectroscopy was utilized to study the equilibrium between the different catalyst states, which explains the measured kinetics of the reaction.