Assembly of Complex Carbocyclic Architectures via Palladium and Nickel-Catalyzed Cyclizations

Citation

Stanko, Allison Michelle (2024) Assembly of Complex Carbocyclic Architectures via Palladium and Nickel-Catalyzed Cyclizations. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/xx1b-9262. https://resolver.caltech.edu/CaltechTHESIS:04292024-194607461

Abstract

Transition metal catalysis can be leveraged to construct challenging chemical bonds with excellent chemo- and stereoselectivity. Herein we describe the discovery of a novel palladium-catalyzed cascade cyclization and a nickel-catalyzed spirocyclization, enabling the assembly of complex carbocyclic architectures. We begin with an introduction describing notable applications of palladium-catalyzed cascade cyclizations in natural product synthesis, enabling the concurrent formation of C–C and C–N bonds in a single synthetic step.

Next, the development of a palladium-catalyzed oxidative Heck/aza-Wacker cascade cyclization is described. This cascade reaction enabled the construction of an all-carbon quaternary center, a C–C bond, and a C–N bond in a single synthetic step. Furthermore, it was employed to build the carbocyclic core of the natural product noraugustamine.

Then, we outline the discovery and optimization of an enantioselective nickel-catalyzed α-spirocyclization of lactones. The established method efficiently and enantioselectively forges 5-, 6-, and 7-membered rings containing all-carbon quaternary centers. This discovery represents an expansion of the synthetic toolkit for enantioselective spirocyclization, providing access to chiral, pharmaceutically relevant spirocyclic products.

Finally, we describe a collaborative project with the Su lab at the University of Arizona in the area of polymer synthesis and gas sensing, where we designed a sensor for the selective detection of gaseous nitric oxide. The sensor’s excellent specificity and part-per-trillion level sensitivity was enabled by novel ferrocene-containing polymeric coatings.

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