Aldol cyclotrimerizations have been used to achieve the rational chemical synthesis of both fullerenes and fullerene fragments in the past. Under certain conditions this reaction produces the corresponding cyclotetramer which has sometimes been regarded as an undesired byproduct. This work details efforts to synthesize and use these cyclotetramers toward a synthesis of a C240 fullerene fragment. One principal focus in this work is tridecacyclene, a cyclic tetramer of acenaphthylene given its name by our group for its thirteen rings. Relatively low yields for the synthesis of tridecacyclene and its derivatives drove us to investigate the mechanism of its formation and attempt to optimize its production. During this process, novel dione products were isolated from the attempted cyclotetramerization of two dimeric species. Characterization of these products by X-ray crystallography gave valuable insight into the reaction pathway, leading us to a new proposed mechanism of formation for the cyclotetramerization products observed in these aldol reactions. β-hydroxy-α-diazoketones are suitable progenitors to vinyl cation intermediates whose use in chemical synthesis is relatively unexplored. As part of an extensive project to develop the chemistry of vinyl cations for use in carbon-carbon bond forming reactions to build important molecular scaffolds, a range of β-hydroxy-α-diazoketones containing a pendent nucleophilic alkene were synthesized. Treatment of these compounds with Lewis acids gave either lactone or cyclopentenone products depending on the substrate used. Proposed herein is a mechanism involving a key acylium intermediate which, depending on the position of the pendent alkene, results in different product outcomes. In a collaborative effort to further investigate the known anti-cancer properties of fusarochromanone, a fungal metabolite that is isolated from Fusarium-infected feed from cold climates, a large-scale synthesis of this natural product was explored. An efficient, scalable synthesis of the previously prohibitively expensive amidochromanone starting material has been achieved and its elaboration to fusarochromanone has been demonstrated.

<p> Mass spectrometry (MS) has become one of the most powerful and versatile tools for chemical analysis due to its ultra-high sensitivity, high throughput, ease of automation, and the large amount of information obtained. Nowadays, MS is extensively used in many tasks, such as identification and quantitation of drug metabolites, analysis of the products of biomass pyrolysis, and study of reactive intermediates, to name a few. However, these mass spectrometric analyses are not without challenges. For example, the requirement for quantifying trace amounts of substances in a complex mixture constantly pushes the detection limit of mass spectrometers, and the increased sample complexity demands higher and higher mass resolution. Therefore, MS is constantly evolving to address more difficult analytical challenges. A variety of MS techniques have been developed over the years, including soft ionization methods that facilitate mass spectrometric analysis of macromolecules, such as proteins and antibodies that enables the development of new therapeutic agents, benchtop high-resolution mass spectrometers, such as the orbitraps that can be used to analyze some of the most complex mixtures, and portable mass spectrometers which can be used in the home and garden and even in cancer surgery. Besides its applications in chemical analysis, MS can serve as a unique tool for the fundamental study of gas-phase ion/molecule reactions, these gas-phase reactions can be used to better understand the reactivities of many reactive intermediates and to obtain structural information for unknown analytes.</p><p></p><p> This thesis is aimed at addressing challenges involved in mass spectrometric analyses of isomeric drug metabolites (Chapter 4), quantitation of drug metabolites by using tandem mass spectrometry coupled with liquid chromatography (LC-MS/MS) (Chapter 5), delineating cellulose depolymerization mechanisms upon fast pyrolysis by using pyrolysis-tandem mass spectrometry (py-MS/MS) (Chapter 6), and studying the reactivities of vinyl cation intermediates (Chapter 7). An overview of the dissertation research is given in Chapter 1, the instrumentation and principles of linear quadrupole ion trap (LQIT) mass spectrometer are discussed in Chapter 2, and the organic synthesis performed for several studies is detailed in Chapter 3.</p>