The neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) protects against the neurotoxicity of MPTP in a mouse model of neurodegeneration. Since 7-NI also inhibits the monoamine oxidase-B (MAO-B) catalyzed bioactivation of MPTP, the role of nNOS inhibition as a mediator of 7-NI's neuroprotective properties have been challenged. In order to examine in greater detail the neuroprotective effects of indazolyl derivatives, the synthesis of water soluble indazolyltetrahydropyridinyl derivatives as potential "prodrugs" that may undergo MAO bioactivation in the brain was undertaken. During the course of the studies on the synthesis of indazolylpyridinium derivatives, precursors to these "prodrugs", an interesting reaction involving the rearrangement of 4-(2H-indazolyl)-1-methylpyridinium iodide to the corresponding 1H-isomer was encountered. A detailed investigation of this rearrangement reaction is reported in this thesis. The syntheses and interaction of nitroindazolyltetrahydropyridinyl "prodrugs" with MAO-B have been investigated previously. Molecular docking studies that attempt to explain the MAO-B substrate and inhibitor properties of members of this series of compounds are described. Finally, the MAO-A substrate properties of nitroindazolyltetrahydropyridinyl derivatives are reported. / Ph. D.

<p>This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ.</p><p>Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields.</p><p>In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates.</p><p>The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three.</p><p>The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.</p>

This thesis summarizes three novel and general reaction protocols for the synthesis of diaryliodonium salts. All protocols utilize mCPBA as oxidant and the acids used are either TfOH, to obtain triflate salts, or BF3•Et2O that gives the corresponding tetrafluoroborate salts in situ. Chapter two describes the reaction of various arenes and aryl iodides, delivering electron-rich and electron-deficient triflates in moderate to excellent yields. In chapter three, it is shown that the need of aryl iodides can be circumvented, as molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. The final and fourth chapter describes the development of a sequential one-pot reaction from aryl iodides and boronic acids, delivering symmetric and unsymmetric, electron-rich and electron-deficient iodonium tetrafluoroborates in moderate to excellent yields. This protocol was developed to overcome mechanistic limitations existing in the protocols described in chapter two and three. The methodology described in this thesis is the most general, efficient and high-yielding existing up to date, making diaryliodonium salts easily available for various applications in synthesis.

This thesis describes novel reaction protocols for the synthesis of diaryliodonium salts and also provides an insight to the mechanism of α-arylation of carbonyl compounds with diaryliodonium salts.  The first chapter gives a general introduction to the field of hypervalent iodine chemistry, mainly focusing on recent developments and applications of diaryliodonium salts. Chapter two describes the synthesis of electron-rich to electron-poor diaryliodonium triflates, in moderate to excellent yields from a range of arenes and iodoarenes. In chapter three, it is described that molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. A large scale synthesis of bis(4-tert-butylphenyl)iodonium triflate is also described, controlled and verified by an external research group, further demonstrating the reliability of this methodology. The fourth chapter describes the development of a sequential one-pot synthesis of diaryliodonium salts from aryl iodides and boronic acids, furnishing symmetric and unsymmetric, electron-rich to electron-poor diaryliodonium tetrafluoroborates in moderate to excellent yields. This method was developed to overcome the regiochemical limitations imposed by the reaction mechanism in the protocols described in the preceding chapters. Chapter five describes a one-pot synthesis of heteroaromatic iodonium salts under similar conditions described in chapter two. The final chapter describes the reaction of enolates with chiral diaryliodonium salts or together with a phase transfer catalyst yielding racemic products. DFT calculations were performed, which revealed a low lying energy transition state (TS) between intermediates, which is believed to be responsible for the lack of selectivity observed in the experimental work. It is also proposed that a [2,3] rearrangement is preferred over a [1,2] rearrangement in the α-arylation of carbonyl compounds. The synthetic methodology described in this thesis is the most generally applicable, efficient and high-yielding to date for the synthesis of diaryliodonium salts, making these reagents readily available for various applications in synthesis.