Mechanistic studies on the combination of enamine and transition metal catalysis

Over the past twelve years, organocatalysis has become a widely adopted technology that allows for the asymmetric formation of carbon--carbon and carbon--heteroatom bonds. Enamine catalysis, in particular, has led to the invention of dozens of efficient and stereoselective processes for bond formation at the alpha-position of a ketone or aldehyde. Although the success of enamine catalysis cannot be overstated, the direct coupling of many valuable moieties, such as simple methyl groups, still remains an unsolved challenge for catalysis based exclusively on chiral secondary amines.;The application of a combination of enamine and transition metal activation is an emerging approach that aims to overcome current limitations. While a number of catalytic schemes can be envisioned based on chemical intuition and existing precedent, a better fundamental understanding of the interaction between enamines and transition metals would provide a valuable foundation, and would hopefully accelerate the process of new reaction discovery. This thesis explores the mechanisms of three distinct transformations that occur using different dual activation strategies. Chapter 2 details a copper-catalyzed reaction where the metal catalyst is intimately involved with both an enamine and an aryl coupling partner in the key bond-forming transition state. Chapter 3 reports on the investigation of an iron-catalyzed reaction, where the metal interacts with only one reaction partner. The lessons learned in Chapter 3 are expanded upon in Chapter 4, where a new, copper-based aldehyde alpha-oxyamination reaction is reported. Finally, Chapter 5 includes studies on the reactivity of enamine radical cations, which are generated by transition metal activation before the bond-forming transition state.