UC Irvine

Abstract of the Dissertation

CO2-Binding by a Bifunctional Guanidine and Bifunctional Alcohol

Employing Chelate Cooperativity

and

Palladium-Catalyzed Enantioselective Carbene Insertion into the N–H Bonds

of Aromatic Amine Heterocyclic and Non-Conjugated Amines

by

Stanley C. Hiew

Doctor of Philosophy

University of California, Irvine, 2019

Professor David L. Van Vranken, Chair

The research described herein consists of two distinct parts. The first part describes the development of a new solution phase system for binding CO2. CO2 capture and sequestration has been proposed as a tool for reducing global CO2 emissions and usually involves separating CO2 from a mixed stream of gasses, such as that encountered in the flue gas of fossil-fueled power plants. The cost of existing CO2 capture technologies has limited their widespread deployment, motivating the search for new reagents and materials that are cheaper, scalable, and more efficient.

The design, synthesis, and CO2-absorption properties of the new solution phase system will be discussed. The system employs a bifunctional guanidine and bifunctional alcohol pair to bind CO2 and uses the principle of chelate cooperativity to elicit unique thermodynamic behavior. The CO2-binding properties of the system were examined at the bulk scale using absorption isotherm measurements, and at the microscopic scale using 1H NMR spectroscopy. Molecular dynamics simulations are presented that provide insight about the intermolecular interaction and aggregation state of the system. Finally, a thermodynamic model is proposed that rationalizes the observed CO2 absorption isotherms.

The second section concerns the development of palladium-catalyzed carbene insertions into the N–H bonds of amines. Amine substrates for such insertion reactions have largely been confined to carbamates and anilines. This section will focus on expanding the substrate scope to include other types of amines. The section will begin by discussing enantioselective carbene insertion into aromatic heterocyclic amines, such as carbazoles and indoles. The reaction employs a palladium(II) catalyst and chiral PyBOX ligand to achieve up to 98% yield and 99% ee.

Next, carbene insertion into benzylic and aliphatic amines will be discussed. Historically, such substrates have proven extremely challenging owing to their tendency of coordinate and deactivate transition metal catalyst. We present a parallel slow addition procedure that permits high yields and moderate ees to be obtained for these types of substrates. The procedure involves simultaneous syringe pump addition of the amine substrate and supplemental palladium catalyst into a stirring solution of palladium catalyst and diazo substrate. This procedure was used to synthesize several morpholine, piperazine, and piperidine aminoester derivatives. Finally, a kinetic model is presented that provides insight into the relationship between amine addition rate, catalyst addition rate, and yield.