Graduation Term

2023

Degree Name

Master of Science (MS)

Department

Department of Chemistry

Committee Chair

Andrew Mitchell

Abstract

The ever-changing world of natural products synthesis and pharmaceutical drug discovery demands the discovery of new and creative synthetic tools. To this end, the current trends towards strictly single stereoisomer synthesis require the advancement of highly stereoselective asymmetric techniques. Cycloaddition reactions are prime targets for asymmetric application owing to their selective formation of multiple contiguous stereocenters through the clockwork establishment of several new bonds in a controlled manner. Furthermore, the unique structural motifs encountered in drug targets are often most elegantly accessed through higher order cycloadditions exercising the distinctive electronic properties of heteroatoms. An example of a cycloaddition of this ilk which requires additional investigation is the dipolar cycloaddition of oxidopyrylium species. The Mitchell group has extensively studied the intramolecular [5 + 2] cycloaddition of oxidopyrylium species generated through the thermal activation of silyloxypyrones. Recent synthetic analysis has successfully exposed two distinct reaction pathways to form the unmistakable oxa-bridged seven-membered cycloadducts of this dipolar cycloaddition.1 Now with a more nuanced understanding of the key factors influencing reactivity, focus has shifted toward the structural nature of the synthesized products. Despite the allure of their highly functionalized seven-membered carbocycle products, current techniques for intermolecular [5 + 2] cycloadditions of this type possess limited substrate scope, functional group tolerance, and stereoselectivity.2 The Mitchell group has sought to employ their intramolecular [5 + 2] expertise to design a cleavable tether for net intermolecular reactions. This work will explore the feasibility and selectivity of [5 + 2] cycloaddition with iminium-based tethers in search of an effective cleavable tether.

Access Type

Thesis-Open Access

DOI

https://doi.org/10.30707/ETD2023.20231004061827540071.999995

Available for download on Tuesday, August 10, 2027

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