Development of Oxidation and Transition Metal-Mediated Reactions and Application to Natural Product Synthesis

Citation

Dibrell, Sara Elise (2023) Development of Oxidation and Transition Metal-Mediated Reactions and Application to Natural Product Synthesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ve4j-tw63. https://resolver.caltech.edu/CaltechTHESIS:04282023-211208336

Abstract

Expedient access to complex molecules via chemical synthesis is important for assessing their biological activity and medicinal properties. In one approach, convergent joining of fragments of similar size and complexity is followed by minimal scaffold tailoring steps to rapidly access natural products. This strategy hinges on the ability to (1) tailor peripheral oxidation, ideally via creative redox transformations, and (2) forge strategic bonds within a complex scaffold through C–C bond formation. We disclose efforts to address these aims by developing broadly useful chemical tools and applying them to the preparation of bioactive natural products.

Toward the first aim, we investigated unusual oxidative reactivity mediated by selenium dioxide. To address the second aim, we developed nickel-catalyzed reductive cross-coupling reactions to study: catalyst-controlled enantioselectivity in the preparation of medicinally relevant small molecules, substrate-controlled stereoselectivity, and selectivity for ring formation. The latter studies enabled the exploration of transition metal-mediated cyclization as a convergent annulation strategy toward the rearranged isoryanodane diterpene (+)-cassiabudanol A, as well as the formal synthesis of the macrocyclic cytotoxin (–)-cylindrocyclophane F.

Thesis Files