Graduation Term

2024

Degree Name

Master of Science (MS)

Department

Department of Chemistry

Committee Chair

Andy Mitchell

Abstract

(5+2) cycloadditions have been a subject of much research interest due to a variety of synthetic applications. This reaction involves the formation of a seven-membered ring carbocycle and it is highly dependent on the choice of the substrates, the reaction conditions, and the catalysts used. The synthetic challenge associated with the (5+2) cycloaddition is mainly due to the difficulty in controlling the regio- and stereo-selectivity of the reaction and can produce multiple products. This reaction often requires harsh reaction conditions, which tend to lead to side reactions and decomposition of the substrates. Despite these challenges, the (5+2) cycloaddition has been successfully applied in the synthesis of several complex natural products. The development of new catalysts and reaction conditions has also improved the efficiency and selectivity of this class of organic reactions, and the Mitchell group is engaged in utilizing temporary tethers towards a net intermolecular oxidopyrylium (5+2) cycloaddition via an intramolecular route. As opposed to the (5+2) intermolecular cycloadditions, (5+2) intramolecular cycloaddition is generally known to occur at lower temperatures due to presence of tether group capable of placing the oxidopyrylium ylide and the alkene in the most feasible orientation required for cycloaddition. Our previous studies have revealed that these reactions are dependent on some factors that are a function of the chemical structure of the oxidopyrylium derivative that is being considered. Still, speculations regarding the reaction pathway of silyloxypyrone-base (5+2) cycloadditions have led us to consider alternate tethers such as the amide tether. The Mitchell group also proposed the ability to cleave the amide bond of these cycloadducts to assist additional promising synthetic routes. Furthermore, the Mitchell group has shown via computational studies that, an enamine underwent a unique intramolecular stepwise mechanism that passes beyond the borderlands of asynchronous concerted mechanism due to an inverse electron demand (5+2) cycloaddition that is controlled by the LUMO of the oxidopyrylium. Based on this observation, an experimental investigation of a unique intramolecular stepwise mechanism was initiated, utilizing an electron withdrawing ester having an amide tether in comparison to the electron donating enamine having a carbon tether.

Access Type

Thesis-Open Access

DOI

https://doi.org/10.30707/ETD2024.20240618063950592713.999936

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Available for download on Tuesday, March 07, 2028

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