HYPERVALENT IODINE-MEDIATED HETEROCYCLIC GROUP TRANSFER REACTIONS TO OXIDATIVE OLEFIN DIFUNCTIONALIZATION

Abstract

The development of new strategies to access pyridinium salts are highly sought out due to their advantageous structures, which have diverse applications across materials science, biological processes, and organic synthesis. As synthetic intermediates, these scaffolds can be used as precursors to valuable piperidine derivatives and have recently emerged as important cross coupling handles for metal-catalyzed processes. Unfortunately, current methods to access pyridinium salts are limited; they require harsh conditions, rely on the presence of an amine functional handle, and are not amenable to diverse structural variation. In Chapter 1, a summary of various syntheses and the reactivity of pyridinium salts is provided. This dissertation provides new strategies to access pyridinium salts. The first method is via aminolactonization of alkenoic acids, resulting in 1° pyridinium salts (Chapter 2). The second method is a regioselective synthesis of 3-aminopiperidine salts via diamination of olefins (Chapter 3). Both methods are promoted by nitrogen-ligated hypervalent iodine reagents (N-HVIs). These novel class of reagents serve as “heterocyclic group transfer reagents,” incorporating diverse pyridinium salts under mild conditions and in excellent yields. Heterocyclic Group Transfer reactions have resulted in new classes of pyridinium salts that can be further functionalized via simple known methods to access diverse piperidine motifs, providing an innovative approach to substitution patterns that were previously challenging to synthesize. These strategies have also enabled pyridinium salts to be viewed as a synthetic platform for diversity-oriented amine synthesis. Chapter 4 will elaborate on the synthesis of different classes of 3-aminopiperidine motifs using hypervalent iodine reagents; these motifs have been previously synthesized using transition metal catalysis.