Enantioselective Reactions of Palladium Enolates and Progress Toward Mitomycin B

Research within the Stoltz group encompasses the total synthesis of natural products and the development of useful enantioselective transformations. This thesis overlaps with these domains in that it describes: 1) the development of several stereoselective reactions of Pd enolates and 2) progress toward the total synthesis of mitomycin B. Specifically, Chapter 1 provides historical context for the development of enantioselective reactions of Pd enolates beyond allylic alkylation within our group. Chapter 2 details the development of an enantioselective 4+2 cycloaddition of Pd enolates generated from prenyl β-ketoesters. Additionally, it describes experimental and computational mechanistic investigations related to the origins of stereoselectivity and the mechanism of catalyst turnover in this transformation. Chapter 3 discloses an enantioselective Michael spirocyclization reaction of Pd enolates as well as a stereoselective intramolecular enone difunctionalization. This method leverages lessons learned from the 4+2 cycloaddition and enables access to a diverse library of stereochemically rich polycycles. Chapter 4 presents our ongoing progress toward the total synthesis of mitomycin B via an isomitomycin approach. Our current strategy involves a key intramolecular nitrile oxide cycloaddition that rapidly constructs a complex framework en route to mitomycin B.