ALLENYL ESTER BUILDING BLOCKS: THEIR APPLICATION TO THE SYNTHESIS OF BRIDGED BICYCLIC COMPOUNDS AND UTILITY AS PRENUCLEOPHILES IN THE DIASTEREOSELECTIVE FORMATION OF ALL-CARBON QUATERNARY ALDOL PRODUCTS

The present dissertation will be largely focused on the synthesis of various [3.2.1] bridged bicycles using allenyl esters. Chapter one will present the importance of various [3.n.1] bridged bicycles in medicinal chemistry. A three-step synthetic route will then be described on how to produce a small library of [3.n.1] bridged bicycles using allenyl esters in an annulation reaction. The [3.n.1] bicyclic diketones can then undergo Grob fragmentation to deliver highly functionalized medium sized rings. Studies towards the total synthesis of vitisinol D, a highly functionalized [3.2.1] bridged bicycle will be discussed. In chapter two, synthesis knowledge gleamed from chapter one will be used to create a model route to form simplified versions of vitisinol D, called resveramorphs. These resveramorphs are structurally similar to resveratrol but possess rigid three-dimensional configuration desired in drug design. The synthetic route to create a variety of resveramorphs will be reported. The sub-nanomolar results of various resveramorph compounds in a Drosophila melanogaster neural tissue model under oxidative stress will be reported. Chapter three will focus on the use of allenyl esters as prenucleophiles to produce triply diastereoselective β-hydroxy esters containing all carbon α-quaternary centers. The challenges in the opitmization of this novel reaction will be described. The relative stereochemistry of the β-hydroxy ester products will be presented using various techniques including X-ray crystallography, 1D NMR, 2D NMR, and force field calculations (MM2). A closed transition state mechanism will be proposed to describe the diastereoselectivity that is observed in the reaction. Additionally, a short indanone synthesis will be shown as a potential application for this novel reaction.