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Highly conjugated, extended heterocycles are recognized as important materials for use in electronic applications, and therefore the synthesis and characterization of new molecules of this type are necessary. One method of forming extended heterocycles relies on the dual cyclizations of the hetero-ene-ene-yne motif. By controlling the reaction conditions, these systems can be made to selectively undergo either a pericyclic reaction to form a cinnoline or a coarctate cyclization to form an isoindazole. The ability of the hetero-ene-ene-yne motif to produce two different heterocycles with distinct properties makes it an attractive system to study. Another method of forming extended heterocycles with tunable properties is by fusing aromatic hydrocarbons with aromatic heterocycles such as thiophene. Chapter I introduces the coarctate reaction and gives an overview of the Haley lab's work in this area. Chapter II explores the dual cyclizations of a phenanthrene-based system. In Chapter III an anthraquinone-based cyclization precursor is used to make diazaheterocycle analogs of tetracene. In Chapter IV isoindazoles were joined by an ethynyl linker to either phenyltriazenes and phenyldiazenes to yield molecules that could undergo both coarctate ring-forming and coarcate ring-opening reactions. Chapter V presents the synthesis and characterization of a series of indacenedithiophenes. Chapter VI advances the synthetic methodology of making larger heteroacenes by presenting work toward heterocyclic pentacene analogs. This dissertation includes both previously published and unpublished co-authored material. / 10000-01-01

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Whilst there are a large number of C-C bond forming reactions available for the construction of heterocycles a number of these protocols require the use of stoichiometric organometallic reagents. Since heterocycles are present in the vast majority of pharmaceutical agents the ability to forge these structures efficiently with a minimal amount of stoichiometric metallic waste is important. With this in mind we initiated a series of projects that focus on the use of [pi]-unsaturates to serve as surrogates to toxic, air and moisture sensitive nucleophilic organometallic reagents utilized in traditional C-C bond forming reactions. This has allowed us to develop catalytic couplings of vinyl azines to imines to form branched amines, to couplings of dimethylallene to isatin forming a tert-prenyl hydroxy oxindole and this neopentyl alcohol can be substituted with C-nucleophiles forming two contiguous quaternary all-carbon centers in our synthetic studies tert-prenyl indole alkaloid natural products. / text

Benzene and its derivatives are ubiquitous in chemical research, with applications ranging from material science to biomedical research. 1,2-Dihydro-1,2-azaborine is a benzene mimic which replaces a CC bond with a BN bond. The basic science and applications of 1,2-azaborines is relatively underdeveloped. This thesis expands the fundamental understanding of 1,2-azaborines. Chapter I describes the air and moisture stability of 1,2-azaborines. Chapter II introduces nucleophilic aromatic substitution reactions that the parent 1,2-dihydro-1,2-azaborine will undergo. Chapter III discusses a trimerization reaction that 1,2-dihydro-1,2-azaborine can perform, which is unique from benzene. Chapter IV examines a novel protection free synthesis of 1,2-azaborines, which provides a more direct route to functionalized 1,2-azaborines. Chapter V discusses the novel deprotection of the N-silicon using an amide, giving one of the first 1,2-azaborine pharmaceutical mimics. Finally, chapter VI summarized miscellaneous contributions I have made to the basic science of 1,2-azaborines. This dissertation includes previously published and unpublished co-authored material. / 10000-01-01

The development of safe and efficient hydrogen storage materials will aid in the transition away from fossil fuels toward a renewable, hydrogen-based energy infrastructure. Boron-nitrogen (BN) containing materials have attracted much attention due to their high hydrogen storage capacity and fast kinetics of hydrogen release. Furthermore, computational studies predict that hydrogen storage materials based on the BN-heterocycle 1,2-azaborine may enable reversible H2 uptake and release, with little additional energy input. This thesis develops the basic science needed for a hydrogen storage platform based on BN-heterocycles such as 1,2-azaborine. Chapter I is a review of recent developments in azaborine chemistry. Chapter II describes a regeneration scheme from a "spent" 1,2-azaborine hydrogen storage material to "fully charged" fuel using molecular H2 and H-/H+ equivalents. Chapter III describes the experimental determination of the resonance stabilization energy of 1,2-azaborines using reaction calorimetry. Chapter IV explores the effect of boron-substitution on the rate and extent of hydrogen release from BN materials. Chapter V describes work on a project unrelated to hydrogen storage, the synthesis and electronic parameter determination of the first 1,2- azaborine-containing phosphine ligand analog. This dissertation includes previously published and unpublished co-authored material.

Verdazyl radicals, discovered in 1963, are a family of exceptionally stable radicals defined by their 6-membered ring containing four nitrogen atoms. Verdazyl radicals are highly modular compounds with a large assortment of substitution patterns reported. Their stability and high degree of structural variability has been exploited in the fields of materials, inorganic, polymer and physical chemistry; however their deliberate use as starting materials towards organic synthesis had only been reported in recent years by the Georges lab. In 2008, the Georges group reported a disproportionation reaction that was observed to a occur with 6-oxoverdazyl radicals resulting in azomethine imines capable of undergoing 1,3-dipolar cycloaddition reactions. With this discovery, the door to using verdazyl radicals as substrates towards organic synthesis had been opened. Their utility in synthesis was soon discovered not to be limited to just the cycloadducts their azomethine imine derivatives could generate but also the increasing number of N-heterocycles that could be generated from these cycloadducts via unique rearrangement reactions, a major theme of this thesis. In addition, triphenyl verdazyl radicals, a distinct class of verdazyl radicals, has been shown to react with alkynes by direct radical addition and rearrangement to afford isoquinolines. As part of this thesis, a new synthetic methodology of generating 6-oxoverdazyl radicals is reported that does not rely on the use of phosgene or hydrazines. This new synthesis allows for the expansion of available alkyl substituents possible on N1 and N5 positions of 6-oxoverdazyl radicals, as well as, generation of unsymmetrical examples of 6-oxoverdazyl radicals with non-identical N1 and N5 alkyl substituents. Employing the new 6-oxoverdazyl radicals synthesized via this method, a study on the effects of different alkyl substituents on the disproportionation reaction of 6-oxoverdazyls was undertaken. Lastly, given the assortment of N-heterocyclic molecular scaffolds capable of being synthesised starting from verdazyl radicals as precursors, the applicability of verdazyl radicals in making a diversity oriented synthesis (DOS) based library was explored. In a group effort with other Georges lab members, a small library composed of various classes of verdazyl radical derived compounds was synthesized and non-specifically tested for cytotoxicity against acute myeloid leukemia and multiple myeloma cell lines in collaboration with The Princess Margaret Hospital. One example was shown to effectively kill cancer cells in both these lines in 250 μM concentration pointing out the potential of using verdazyl radical based chemistry in drug discovery.

Verdazyl radicals, discovered in 1963, are a family of exceptionally stable radicals defined by their 6-membered ring containing four nitrogen atoms. Verdazyl radicals are highly modular compounds with a large assortment of substitution patterns reported. Their stability and high degree of structural variability has been exploited in the fields of materials, inorganic, polymer and physical chemistry; however their deliberate use as starting materials towards organic synthesis had only been reported in recent years by the Georges lab. In 2008, the Georges group reported a disproportionation reaction that was observed to a occur with 6-oxoverdazyl radicals resulting in azomethine imines capable of undergoing 1,3-dipolar cycloaddition reactions. With this discovery, the door to using verdazyl radicals as substrates towards organic synthesis had been opened. Their utility in synthesis was soon discovered not to be limited to just the cycloadducts their azomethine imine derivatives could generate but also the increasing number of N-heterocycles that could be generated from these cycloadducts via unique rearrangement reactions, a major theme of this thesis. In addition, triphenyl verdazyl radicals, a distinct class of verdazyl radicals, has been shown to react with alkynes by direct radical addition and rearrangement to afford isoquinolines. As part of this thesis, a new synthetic methodology of generating 6-oxoverdazyl radicals is reported that does not rely on the use of phosgene or hydrazines. This new synthesis allows for the expansion of available alkyl substituents possible on N1 and N5 positions of 6-oxoverdazyl radicals, as well as, generation of unsymmetrical examples of 6-oxoverdazyl radicals with non-identical N1 and N5 alkyl substituents. Employing the new 6-oxoverdazyl radicals synthesized via this method, a study on the effects of different alkyl substituents on the disproportionation reaction of 6-oxoverdazyls was undertaken. Lastly, given the assortment of N-heterocyclic molecular scaffolds capable of being synthesised starting from verdazyl radicals as precursors, the applicability of verdazyl radicals in making a diversity oriented synthesis (DOS) based library was explored. In a group effort with other Georges lab members, a small library composed of various classes of verdazyl radical derived compounds was synthesized and non-specifically tested for cytotoxicity against acute myeloid leukemia and multiple myeloma cell lines in collaboration with The Princess Margaret Hospital. One example was shown to effectively kill cancer cells in both these lines in 250 μM concentration pointing out the potential of using verdazyl radical based chemistry in drug discovery.

La thèse est divisée en deux parties distinctes.La première consiste, après une étude exhaustive concernant les réactions de désulfurisation de thiocétals répertoriées dans la littérature, a montré que l'association TMSCl/NaI est une méthode de choix moderne pour réduire les thiocétals puisqu'elle ne nécessite aucun métal toxique. Dans une plus longue partie, nous nous sommes interressés à la synthèse d'hétérocycles (isocoumarines, benzothiophènes et indoles) par l'étude de réactions originales d'hétérocyclisation. La thèse est présentée sous forme du publications (7). / This thesis is divided into two distinct parts. The first show that, after a comprehensive study of thioketals desulfurization reactions listed in the literature, the use of TMSCl / NaI combination is a modern method of choice to reduce thioketals since it does not require any toxic metal. In a second part, we have been interested in the synthesis of heterocycles (isocoumarins, benzothiophenes and indoles) by the study of original heterocyclization reactions. The thesis is presented with the presentation and discussion of publications (7).