Stereoselective Synthesis of α- and β-Functionalized Carbonyl Derivatives: Allylic Alkylation of Dialkyl Malonates, Total Synthesis of Hunterine A, and Progress Toward the Synthesis of Kuroshine A

Research in the Stoltz group generally focuses on the synthesis of complex molecules enabled by the discovery and application of new synthetic methodologies. The majority of the research described in this thesis encompasses variations on this unifying central theme. Chapter 1 focuses on the development of new asymmetric methodology for the synthesis of stereogenic all-carbon quaternary centers through the application of iridium catalysis. A key advance was the use of malonate nucleophiles and bis-alkyl substituted electrophiles, two inputs commonly employed in allylic alkylation chemistry that had yet to be utilized for the synthesis of quaternary carbon centers. Chapter 2 describes the development and execution of a synthetic strategy for the asymmetric construction of a rearranged monoterpene indole alkaloid, hunterine A. Key to the assembly of this molecule were an enantioselective desymmetrization, aza-Cope/Mannich rearrangement, azide-alkene dipolar cycloaddition, and regioselective aziridine opening. Chapter 3 details an investigation born out of an observation of a regioselective aziridine opening during the course of the synthesis of hunterine A. This research focuses on the synthesis of sterically unbiased fused bicyclic N-aryl aziridines and their reactivity in a variety of ring opening reactions. Chapter 4 and Appendix 7 describe ongoing efforts toward the synthesis of Kuroshine A and other highly oxidized zoanthamine alkaloids. The synthetic strategies described focus on evaluating formation of the ABC ring system of the molecule via a masked ortho-benzoquinone cycloaddition.