Date of Award

1-1-2012

Document Type

Campus Access Dissertation

Department

Chemistry and Biochemistry

Sub-Department

Chemistry

First Advisor

Sheryl L Wiskur

Abstract

This dissertation describes our efforts to develop new methods of producing enantiopure compounds through a sequential one-pot polishing procedure and through kinetic resolutions via silylation and desilylation. Chapter 2 highlights how we have combined a moderately selective asymmetric reaction (either a reduction or allylation) with a kinetic resolution (via acylation or silylation) to generate enantiopure compounds (enantiomeric excess (ee) >95%) with yields greater than 50%. The enantioselective reaction produces a compound with moderate ee's that is "polished" to a high ee by the kinetic resolution. Combining the moderately selective reactions together in this sequence overcomes the inherent disadvantages of the individual reactions (low ee and yield) and allows researchers to quickly produce enantiopure materials without developing and optimizing a new methodology.

In Chapter 3, we describe our attempts at developing an enantioselective desilylation to produce enantiopure silyl ethers through the use of chiral fluoride phase transfer catalysts. Initially, desilylation was attempted with a variety of commercially available catalysts and fluoride sources including: ammonium salt catalysts with potassium fluoride, nucleophilic catalysts with benzoyl fluoride, and an ammonium fluoride salt complex. While desilylation was achieved with the catalysts and fluoride sources, none of the reactions were enantioselective. As a result, new catalysts were designed to work together with potassium fluoride to enantioselectively desilylate the silyl protected alcohols. The catalysts were designed to include a polyether linkage and thiourea so they could bring the fluoride ion into solution while hydrogen bonding to it to reduce reactivity and increase the enantioselectivity. The design, synthesis, and progression of the novel catalysts are discussed.

Enantiopure compounds were also generated through the use of the silylation based kinetic resolution procedure developed in 2011 by the Wiskur lab. Chapter 4 discusses how this enantioselective system has been applied to the kinetic resolution of α-hydroxy carbonyl compounds. Initial results exhibited good to high selectivity factors (s = 10-32) with the benzotetramisole catalyst and α-hydroxy lactone substrates. The synthesis of other α-hydroxy carbonyl substrates has been attempted through the use of several oxidation reagents. These studies are currently ongoing but they should offer valuable insight into designing better and more selective catalysts and kinetic resolution procedures to generate enantiopure materials.

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