Date of Award

Winter 12-19-2022

Document Type

Thesis (Ph.D.)

Department or Program


First Advisor

Glenn C. Micalizio


Natural products, specifically complex, carbocyclic natural products, have served as the inspiration for novel methods development for decades. Over that time, metallacycle-mediated cross-coupling has arisen as a powerful means for the synthesis of fused carbocycles. This work details three methods for the synthesis and functionalization of carbocyclic motifs that have been enabled by Ti-mediated cross-coupling reactions. The first of these studies include a complementary method to the Pauson–Khand reaction for the synthesis of highly substituted cyclopentenones via Ti-mediated alkyne–β-ketoester coupling. The second project, a modern approach to steroidal tetracycles, will be discussed that features: (1) an alkoxide-directed metallacycle-mediated [2+2+2] annulation reaction, and (2) a double asymmetric Friedel–Crafts cyclization for stereoselective steroidal C9–C10 bond formation. The final project discussed was inspired by the cardenolide and bufadienolide families of tetracyclic triterpenoid natural products and features a unique syn-SN2’ addition reaction of cyanocuprates with steroidal C14–C17 vinylepoxides.