Development of oxidative methodologies and application toward tetrodotoxin core

This thesis covers a novel approach to tetrodotoxin that relies on the oxidative amidation of a phenol and intramolecular nitrile oxide cycloaddition to install a β-hydroxynitrile unit among the key steps. These transformations, and others contained herein, effectively set the tetrasubstituted C-8a stereocenter, as well C-4a formyl equivalent and C-5, C-7 and C-8 hydroxyl groups. Novel reaction types were developed in the course of this work, including a new method for the oxidation of oximes to nitrile oxides using hypervalent iodine reagents. Additionally, I identified a tandem reaction sequence, involving the dearomatization of a phenol, followed by [3+2]-dipolarcycloaddition, the first of its kind. This tandem sequence proved a powerful tool for the rapid construction of multicyclic compounds from structurally simpler starting materials. These studies resulted in advanced intermediates which contained much of the structure of the tetrodotoxin core.Science, Faculty ofChemistry, Department ofGraduat