Efficient Synthetic Transformations Enabled by Group X Catalysis

Author: Sharp, Kimberly Rhian

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Stoltz, Brian M.

Committee Members: Reisman, Sarah E.; Fu, Gregory C.; Manthiram, Karthish; Stoltz, Brian M.

Option: Chemistry

Abstract

The development of efficient routes for the synthesis of complex molecules is a central theme of organic chemistry research. Herein, we describe our efforts toward this goal through the demonstration of umpolung strategies for incorporation of nitrogen functionality. Chapter 1 describes nickel-catalyzed N–N cross coupling for the synthesis of hydrazides, tolerant of complex coupling partners. Mechanistic investigation suggests a Ni (I) active catalyst, capable of forming a key nitrenoid intermediate. Chapter 2 details an enolate amidation method, efficiently forming a bond between complex amides and the α-position of β-keto esters. Nickelocene catalysis is used, and we hypothesize that it acts as a single electron reductant to form an active N-centered radical species. Appendix 4 conveys initial attempts at producing enantioenriched α-amidated products with palladium-catalyzed decarboxylative allylic alkylation. Chapter 3 reports our investigations in applying our N–N coupling to the synthesis of the complex indole alkaloid braznitidumine, featuring a hydrazine in its central 10-membered ring. Strategies for the formation of the desired indole coupling partner and the necessary fused imidazolidine-pyran motif are discussed. Chapter 4 outlines our efforts toward the synthesis of hypatulone A, a rearranged polycyclic polyprenylated acylphloroglucinol. We propose a key palladium-catalyzed carbonylative coupling for the formation of the caged core, and detail our efforts toward the synthesis of the requisite bicyclo[3.3.1]nonane.