Rearrangement reactions of dihydrofuranyl and dihydropyranyl carbinols: Mechanistic studies and application to the synthesis of natural products and novel carbohydrates

Rearrangement reactions are one of the most powerful methods of structural assembly available to synthetic organic chemists. Often, they proceed with high stereoselectivity and allow the construction of complex frameworks that are difficult or impractical to access by other methods. The recent discovery of a new rearrangement process that constructs spirocyclic structures from tertiary allylic alcohol precursors has spawned several mechanistic investigations and synthetic applications.; This work describes an examination of the novel spirocyclization in four areas. The first part of the research focuses on the issue of chirality transfer from the vinyl ether to the incipient quaternary center. The vinyl ethers employed address the issue on a more fundamental level than previous work as they do not include heteroatom substituents which have been shown to undergo side reactions. Other effects such as hydrogen bonding between the free hydroxyl proton and the oxo ether substituents and dipolar interactions which may alter the course of the rearrangement are also avoided. Utilization of two products of this study in the total synthesis of both the cis and trans isomers of theaspirone constitute the second component of the presentation.; The third aspect of the project deals with a rearrangement-functionalization approach to keto spiro ethers with functionality introduced into the ether ring during the rearrangement. To this end, a bromonium ion-induced rearrangement has been employed in the production of halogenated keto spiro ethers. In addition to probing the limitations of this strategy, attention has been given to the prospect of "cascade chirality transfer" in which other substituents on the ether ring are used to influence the stereochemistry of the intermediate bromonium ion and, ultimately, the relative configuration of the quaternary carbon atom. The final segment of the dissertation addresses studies directed toward the application of the rearrangement-functionalization methodology to the synthesis of novel spirocyclic sugar derivatives and nucleosides.