Enantioselective Reactions of Palladium Enolates and Progress Toward Mitomycin B

Author: Strong, Christian Santiago

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Stoltz, Brian M.

Committee Members: Fu, Gregory C.; Reisman, Sarah E.; Hsieh-Wilson, Linda C.; Goddard, William A., III; Stoltz, Brian M.

Option: Chemistry

DOI: 10.7907/gwac-qk95

Abstract

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.

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