Date of Award
Master of Science (MS)
Department of Chemistry
Andy A.M. Mitchell
Over the last decade, several developments and advancements have been made towards oxidopyrylium-based [5 + 2] cycloadditions which allow for the synthesis of natural products. Dearomative oxidopyrylium-based [5 + 2] cycloadditions allow the formation of complex polycyclic compounds from readily available aromatic rings in a single step. Dearomatization of electron rich aromatic systems directly adds functionality resulting in complex compounds with increased levels of stereogenic centers and chemical space. These structural features represent privileged complexes in drug discovery and development. Some major difficulties associated with these reactions are the disruption of the aromaticity of arenes, controlling the regioselectivity and stereoselectivity of the reaction, functional group compatibility and overcoming steric hindrance. These setbacks demand new reaction pathways and improvements to attain greater efficiency. In this regard, this study reports a dearomative [5 + 2] cycloaddition which involves thermal activation of amide-tethered intramolecular substrates that enables increased efficacy and scope. Effort towards this work entails synthesis of silyloxypyrone-amides which when subjected to dearomative conditions, affords the corresponding cycloadduct. In both cases of indole and furanbased dearomative studies, it became evident that less hindered silyloxypyrone amides yielded lower conversion rates to cycloadduct formation than bulky amides. Another aspect which emerged from our dearomative studies pertains to amide and N-O tethered tethered intramolecular [5 + 2] cycloadditions. Furthermore, our efforts of synthesizing of amide and N-O tethered silyloxypyrones cycloadduct have proven fruitful. A key factor contributing to this success is the ability to vary the substituent on the substrate, enabling the generation of diverse cycloadducts.
Erzuah, Marymoud, "Dearomative | Amide | N-o Tethered Oxidopyrylium [ 5 + 2 ] Cycloaddition Reactions" (2023). Theses and Dissertations. 1850.