Access Type

Open Access Dissertation

Date of Award

January 2014

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

Matthew J. Allen

Abstract

The formation of carbon-carbon bonds is of great interest to synthetic chemists because these bonds make up the majority of biologically active compounds. The Mukaiyama aldol reaction is a Lewis-acid-catalyzed carbon-carbon bond-forming reaction that has the ability to produce optically active β-hydroxy carbonyls which can be found in many pharmaceuticals and natural products. Because of precatalyst instability towards hydrolysis, anhydrous solvents are commonly used. Recent efforts have focused on water-tolerant versions of enantioselective Mukaiyama aldol reactions because of the financial and environmental benefits of using aqueous media. Consequently, the Lewis-acidic and water-tolerant features of Ln3+ ions have aroused great interest in lanthanide-catalyzed bond-forming reactions in aqueous media.

Several Ln3+-based Lewis acid precatalysts that were designed for Mukaiyama aldol reactions have been shown to be enantioselective, water-tolerant, and recoverable. Limiting the usefulness of these precatalysts are high ligand loadings and long reaction times that are necessary for high enantiomeric ratios. An understanding of water-coordination number, counter anion identitiy, solvent system, and ligand type effect(s) are necessary to improve upon existing Ln3+-based precatalysts.

I used luminescence-decay measurements and high performance liquid chromatography analyses to study the effects of water-coordination number, counter anion identitiy, and solvent system on reaction rates of Mukaiyama aldol reactions. I found that higher water-coordination numbers and higher water compositions gave rise to more reactive precatalysts for Mukaiyama aldol reactions that were catalyzed by Eu3+. I synthesized and characterized four new hexadentate ligands to study the effects of ligand type on reactivity and selectivity of Eu3+-based precatalysts for Mukaiyama aldol reactions. I used Eu3+ emission spectra and 1H-NMR experiments to study changes in Eu3+ coordination while titrating hexadentate ligands into solutions of Eu3+ and I found that Eu3+ is able to be coordinatively saturated in the presence of excess hexadentate ligands.

By studying Eu3+ in the presence of different anions and several chiral hexadentate ligands that contain ester, carboxylic acid, alcohol and amide donating groups I was able to find trends in reactivity and selectivity. In this thesis I describe the results that are likely to contribute to the development of highly reactive and selective Ln3+-based precatalysts.

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