This renewal project centers on electrochemically mediated oxidative cyclization reactions. Syntheses of the natural products arteanuinn B and arteanuin M will be used to explore the generality of the synthetic strategy employed in the construction of alliacol A, a synthesis of artemisolide will be used to probe the synthetic utility of "Curtin-Hammett controlled" cyclizations, a synthesis of ineleganolide will be used to study the utility of enediol initiating groups for the cyclizations, and a synthesis of dankasterone will be used to determine the compatibility of anodic cyclizations with electron-withdrawing groups on the initiating olefin. Efforts to expand the scope of the cyclization reactions will be pursued, tuning the reactivity of the radical cations so that they favor carbon - carbon bond formation in an effort to overcome the twin barriers of six-membered ring and quaternary carbon formation. Both electron-rich ketene acetals and enamines will be oxidized and the resulting radical cations trapped with allylsilane nucleophiles. Product analysis of the ensuing reactions will be used along with cyclic voltammetry to probe both the nature of radical cation intermediates and how their subsequent reactions can be manipulated.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Kevin D. Moeller of the Department of Chemistry at Washington University. Professor Moeller and his students will explore the use of electrical energy to induce selective reactions of organic molecules. Electrochemically mediated reaction sequences will be developed which allow the efficient synthesis of chosen organic molecules. Such organic electrochemical reactions offer promise as simple yet highly versatile tools for the construction of the complex target structures forming the basis of modern pharmaceutical research. Electrochemical methods also offer promise as potentially "green" (environmentally benign) approaches for organic synthesis.
