Mechanistic Investigations of Isothiourea Catalyzed Silylations of Secondary Alcohols Using Reaction Progress Kinetic Analysis

The primary focus of this research is in expanding the knowledge and scope of the asymmetric silylation of alcohols. Since it was discovered in 2011 that chiral isothioureas can selectively silylate alcohols through kinetic resolution reactions, the Wiskur group has been working to increase the applications of the methodology. Understanding the kinetics behind the mechanism of the reaction is fundamental in the designing both improved kinetic resolutions and other silylation methodology. Chapter 2 focuses on using reaction progress kinetic analysis to monitor silylations of secondary alcohols with thiourea catalysts in real time using in situ IR to determine the rate of reaction and give insight to how the components of the reaction work together so that a reaction mechanism can be proposed. Additives and derivatizations of the original silylation reaction gives a new understanding of how the reaction may be affected by manipulation of the sterics and electronics inherit in the system.Chapter 3 contains new projects that seek to expand the chiral isothiourea catalyzed silylation methodology beyond the traditional kinetic resolution, first by examining the potential for a more efficient parallel kinetic resolution where a single catalyst can be used to catalyze two simultaneous reactions. It is demonstrated that the acylation reaction and silylation reaction target opposite enantiomers with the same catalyst. The selective silylation of one alcohol in the presence of three of hexose monomers is also explored. Improvement on the selectivity by increasing the sterics of the electrophile was seen while discovering a catalyst that also improves selectivity is still being conducted.Finally, the synthesis of a new pyridine containing macrocycle that binds to glutamate, producing a measurable electrochemical signal is also shown. Copper (II) cations are introduced into the macrocycle that have shown a strong affinity for glutamate. An alkyne derivative of the macrocycle is produced for the covalent attachment to an electrochemical probe to be used by our collaborators in the in vivo detection of glutamate.