Date of Award

8-9-2014

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

First Advisor

Sheryl L. Wiskur

Abstract

This dissertation represents our preliminary mechanistic investigations on the silylation-based kinetic resolution of secondary alcohols, and how we use that knowledge for further expansion of this methodology. Chapter 2 describes how we came up with a preliminary mechanism of our silylation-based methodology using a linear free energy relationship and a rate study. In this chapter, several para substituted triphenylsilyl chlorides were prepared that varied electronically and sterically in order to understand the substituent effects on the rate and the selectivity of the reaction. Selectivity factors and initial rates were experimentally determined for the kinetic resolution reactions with the newly designed silyl chlorides. Linear free energy relationships were found to correlate both selectivity factors and initial rates.

Chapter 3 covers our 29Si NMR studies in order to understand if a complex is forming between the catalyst (-)-tetramisole and Ph3SiCl. A variety of different techniques were used including 1H NMR titrations, 29Si NMR experiments, and 1H-29Si gHSQC 2D experiments. Finally, three different mechanisms were proposed for future study.

Chapter 4 discusses our efforts to apply the silylation-based methodology developed by the Wiskur lab to allylic alcohols, homoallylic alcohols, and 2-arylcyclohexanols. No enantiodiscrimination was obtained with allylic alcohols and homoallylic alcohols while a moderate level of selectivity was achieved with 2-arylcyclohexanols. Employing Ph3SiCl substituted in the para position with an isopropyl group in the kinetic resolution reaction of 2-arylcyclohexanol resulted in a doubling of the selectivity factor. The synthesis of various substrates and employing them in our kinetic resolution is discussed.

Chapter 5 describes the use of a polymer supported triphenylsilyl chloride in our kinetic resolution reaction. Different molecular weight polymers containing triphenylsilyl chloride were prepared and tested in the kinetic resolution of 4-chromanol. Similar selectivity factors were reported in all cases. Reaction optimization along with future work for this project is discussed.

Finally, Chapter 6 explores our attempt toward the development of a kinetic resolution of amines by transforming them into imines and employing them in an asymmetric aza-Diels-Alder reaction. Various chiral Lewis acids were attempted to achieve selectivity in the aza-Diels-Alder reaction.

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