Reagents based on Ce(IV) represent some of the most utilized oxidants in organic synthesis. In spite of this, very little is known about the mechanism of these reagents and as a result, full utilization of Ce(IV) in oxidative bond-forming reactions is limited. In order to understand Ce(IV) reagents at a basic level, it is important to determine the dependence of aggregation states, relative stabilities of reactants and the rate- limiting transition structures on the solvent medium. An intimate understanding of the interrelationship between the effect of ligands on the oxidizing power Ce(IV), the influence of solvent, and the rates (mechanisms) of the various available pathways, will make it possible to fine tune the variables so that reactions mediated by Ce(IV) lead to desired products. The studies described herein are directed towards understanding the relationships between these variables and the rates and selectivities of Ce(IV)-mediated oxidations and oxidative bond-forming reactions so that favorable reaction outcomes can be predicted.
Specific Aim 1 describes studies that define the role of ligands and solvent on the solution structure and reactivity of Ce(IV) oxidants.
Specific Aim 2 presents rate studies designed to determine not only the rate order and mechanism of substrate oxidation by Ce(IV) reagents, but the degree to which Ce-based oxidants interact with substrate along the reaction coordinate. The data obtained from these studies will be used to investigate the mechanism of radical and radical cation addition to olefins.
Specific Aim 3 describes the development of both known and novel synthetic protocols utilizing mechanistic data obtained in Specific Aims 1 and 2. In particular, synthetic approaches to heterocycles, tandem ring expansion-addition reactions, and mild oxidations initiated by Ce(IV) will be explored. The long term goal of this project is to provide the insight necessary to develop stereoselective reactions and protocols that use substoichiometric amounts of Ce(IV). The thorough mechanistic analysis as proposed herein, will significantly expand the scope and utility of Ce(IV)-based oxidations and oxidative bond-forming reactions, and potentially lead to novel synthetically useful transformations and methods for the synthesis of biologically active substrates. ? ?
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