Lanthanide-Based Precatalysts For Carbon-Carbon Bond-Forming Reactions In Aqueous Media

<p>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.</p> <p> 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.</p> <p> 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. </p> <p>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.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2014

Author dc:creator

• Averill, Derek James

Contributors dc:contributor

• Matthew J. Allen

• Aqueous
• Asymmetric
• Catalysis
• Europium
• Lanthanide
• Mukaiyama
• Chemistry

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/1084

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-2083