The Design of Reactions, Catalysts and Materials with Aromatic Ions (2014)

This thesis details the use of aromatic ions, especially aminocyclopropenium ions, as empowering design elements in the development of new chemical reactions, organic catalysts and polymeric materials. A particular focus is placed throughout on understanding the relationship between the structure of aromatic ions and their performance in these novel applications. Additionally, the benefits that aromatic ions provide in these contexts are highlighted. The first chapter briefly summarizes the Lambert Group's prior efforts toward exploiting the unique reactivity profiles of aromatic ions in the context of new reaction design. Also provided in the first chapter is a comprehensive literature review of aminocyclopropenium ions, upon which the majority of advances described in this thesis are based. To set the stage for the first application of aminocyclopropenium ions, Chapter 2 provides an account of existing highly Brønsted basic functional groups, including guanidines, proazaphosphatranes and iminophosphoranes. The provided review on the synthesis and use in asymmetric catalysis of these bases indicates that there is a high need for conceptually new Brønsted basic functional groups. To address this need, the development of chiral 2,3-bis(dialkylamino)cyclopropenimines as a new platform for asymmetric Brønsted base catalysis is described in Chapter 3. This new class of Brønsted base is readily synthesized on scale, operates efficiently under practical conditions, and greatly outperforms closely related guanidine-based catalysts. Structure-activity relationship studies, mechanistic experiments and computational transition state modeling are all discussed in the context of asymmetric glycinate imine Michael reactions in order to arrive at a working model for cyclopropenimine chemistry. Cumulatively, this chapter provides a "user's guide" to understanding and developing further applications of 2,3-bis(dialkylamino)cyclopropenimines. The use of our optimal chiral 2,3-bis(dialkylamino)cyclopropenimine catalyst to promote asymmetric Mannich reactions of glycinate imines and N-Boc-aldimines is described in Chapter 4. The products of this transformation are optically enriched diamino acid derivatives, an important motif widely utilized in medicinal and synthetic chemistry. Importantly, unlike existing methods, our technology promotes reactions between tert-butyl glycinate and aliphatic N-Boc-aldimine substrates. A preparative-scale reaction is demonstrated and derivatization of its product to several valuable chiral compounds is shown. Chapter 5 describes the use of tris(dialkylamino)cyclopropenium (TDAC) ions as a new class of onium-like catalyst. A simple TDAC chloride salt is prepared on a 75-gram scale and its use as a phase transfer catalyst for a variety of reactions is demonstrated. This same salt is also utilized as an epoxide opening catalyst for a variety of transformations, including the fixation of carbon dioxide. Chapter 6 briefly highlights several continued applications of the chemistry advanced throughout this thesis. First, the work of other members of the Lambert Group toward the continued development of cyclopropenimine chemistry is described. Second, a broad initiative between the Lambert and Campos Groups at Columbia University focused on the synthesis and application of TDAC-based polymers is introduced. Lastly, the identification of a previously unknown equilibrium between fulvenes and imines/aldehydes in the context of a new mode of catalysis is presented.