UC Berkeley

The following dissertation is presented in four chapters each examining individual research projects.Chapter 1 describes our initial efforts toward the total synthesis of the antiviral marine alkaloid dragmacidin F via an early stage deconstructive functionalization approach of 5-hydroxy-2- adamantanone to rapidly access the bicyclo[3.3.1]nonane core of the natural product. Further proposed steps include a Trofimov pyrrole synthesis followed by various C–H functionalization reactions to obtain the western fragment of the desired target molecule.Chapter 2 details the development and successful application of a novel oxidative C=N π-bond cleavage using photoexcited nitroarenes to convert ketoximes into their parent ketones. Given the importance of ketoximes as powerful directing groups, the practicality of this method is underscored in its use during a revised total synthesis of Cephalotaxus norditerpenoid cephanolide D. Additionally, a mechanistic study including isotopic labeling as well as an in-depth photophysical analysis is presented. Chapter 3 discusses a mechanistically driven development of a complementary reductive amination reaction, which reductively aminates the C–C σ-bond of carbonyls (as opposed to the carbonyl C–O π-bond) generating value-added linear and cyclic 3° amines in a modular fashion. Chapter 4 presents a novel and highly modular C–C cleavage /cross coupling strategy to access medium-to-large sized ring systems enabled by a strain release (ground state raising) and palladium-mediated templating approach. A variety of functional groups are tolerated in this reaction and the strategy could ultimately be employed in the total synthesis and structural revision of various resorcylic acid lactone (RAL) natural products. DFT calculations were used to support a proposed reaction mechanism.