Access Type

Open Access Dissertation

Date of Award

January 2012

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

Matthew J. Allen

Abstract

Lewis acid catalyzed carbon-carbon bond-forming reactions are of great interest in organic synthesis. However, many conventional Lewis acids, and almost all enantioselective Lewis acid catalysts, must be used under strictly anhydrous conditions to avoid hydrolysis and the difficulties associated with recovery and reuse of the catalysts. Due to these drawbacks of conventional Lewis acids, there is a growing desire to perform many organic transformations using more environmentally friendly aqueous-stable catalysts. The advantages of using aqueous-stable catalysts include the ability to use unprotected functional groups, ease of product separation and catalyst recovery, and avoidance of costly solvent drying procedures. Lanthanide trifluoronmethanesulfonates (triflates), Ln(OTf)3, address this goal because they are water-tolerant Lewis acid precatalysts that can catalyze a wide range of important carbon-carbon and carbon-heteroatom bond-forming reactions such as the aldol, nitro-aldol, Mannich, Diels-Alder, Michael, Mukaiyama aldol, and Friedal-Crafts reactions due to their hard, electrophilic, and hydrolysis-stable character.

Despite their favorable properties, the use of lanthanide triflates in asymmetric carbon-carbon bond formation under aqueous conditions has been limited due to lack of mechanistic understanding of these precatalysts in aqueous solution: the influence of counter ion coordination, the effect of solvent coordination, and the identification of intermediates in the catalytic cycle. Further, identification of the rate-determining step and product-dissociation rate of aqueous lanthanide triflate-based catalysis is of fundamental importance for developing more efficient catalysts.

I adapted luminescence-decay measurements to enable the study of the mechanism of lanthanide-based precatalysts in aqueous systems. Because the number of water molecules coordinated to the lanthanide ion is critical to more thoroughly understanding the nature and the reactivity of lanthanide-based precatalysts, I used luminescence-decay studies to measure the dynamics of water molecules coordinated to lanthanide-ions throughout the catalytic cycle of a selected Mukaiyama aldol reaction. Using these luminescence-decay measurements, I determined equilibrium constants as well as structural and mechanistic information regarding lanthanide-based chiral catalytic systems in aqueous medium. Furthermore, I used this analytical tool to study the influence of the coordination environment of europium-based precatalysts including europium nitrates, chlorides, and acetates on reaction rate and yield. I also empirically derived equations that enable fast and accurate determination of the water-coordination number of lanthanides in binary solvent systems. In summary, I adapted luminescence-decay measurements to probe the coordination environment of europium-based precatalysts in aqueous media and the details of my efforts are described in this thesis.

The other analytical tool described in this thesis involves the use of 17O NMR spectroscopy with variable temperature for the determination of important exchange rates in lanthanide-catalyzed reactions. The results described in this thesis demonstrate the utility of these two powerful analytical tools to study aqueous, lanthanide-catalyzed bond-forming reactions.

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