Document Type


Date of Degree Completion

Spring 2024

Degree Name

Master of Science (MS)



Committee Chair

Dr. Timothy K. Beng

Second Committee Member

Dr. Gil Belofsky

Third Committee Member

Dr. Levente Fabry-Asztalos


Functionalized tetrahydropyrans are structural motifs in diverse natural products, including polyether antibiotics, marine toxins, pheromones, and pharmaceuticals. They are frequently used as versatile building blocks for accessing stereochemically sophisticated biologically active compounds. Specifically, functionalized bicyclic tetrahydropyrans bearing contiguous stereocenters have garnered interest in the synthesis and medicinal chemistry communities. Thus far, some synthetic methods have been developed for their construction and functionalization. These methods include Prins' cyclization reactions, intramolecular oxa-Michael reactions, hetero-Diels-Alder cyclization, ring-closing metathesis, radical cyclization, and halocycloetherification. However, these methods have some drawbacks such as the need for expensive reagents and catalysts, substrate limitations, and environmentally unfriendly conditions. Seeking to develop a new strategy to produce lactam-fused tetrahydropyrans, we successfully designed a modular, cost-saving, transition metal-free, and environmentally friendly approach that leverages the 1,3-azadiene-anhydride annulation reaction. Suitable reaction conditions were successfully investigated for the halocycloetherification of trisubstituted lactam-bearing tertiary alkenols to access bicyclic tetrahydropyrans in good yields, regioselectivities, and diastereoselectivities. The requisite bromoethers were then engaged efficiently in a dehydrobromination protocol, leading to the syntheses of highly substituted lactam-tethered 3-methylenetetrahydropyrans, which are highly prevalent in pharmaceuticals and materials. We anticipate that this versatile synthetic method will be embraced by the organic and medicinal chemistry communities. We have laid the foundation for a future structure-activity relationship (SAR) study through collaborative efforts. The ultimate goal is to find new therapeutics for several diseases, including diabetes mellitus.

Available for download on Saturday, June 13, 2026