This is a renewal project in the Organic and Macromolecular Chemistry Program. Dr. Swenton is studying electrode reactions as a means of producing new synthetic reactions for the synthesis of complex natural products. The use of electrochemical reactions can make the synthesis more efficient and potentially less polluting because greater control can be exercised over the reagents. This program is comprised of two major areas of research. One part concerns the anodic oxidation of anilide derivatives and the chemistry of the products formed in these reactions. Preliminary work has established that high yields of 1,4-addition products are formed from anodic oxidation of two p-methoxyanilide derivatives. Anodic oxidation of p-methoxyanilides in methanol in the presence of lutidine serves as a general route to quinone imide ketals. These moieties undergo 1,2- addition of organolithium reagents and 1,4-addition of malonate anion in high yields. The work involves an in-depth study of the anodic oxidation of anilides. The chemistry of the products from these anodic oxidations will be investigated. These reactions not only serve as versatile methods for obtaining uniquely functionalized anilides but also will provide new approaches to ring systems present in many natural products. The second area of major emphasis focuses on methods for carbon-carbon bond formation from transient intermediates generated from anodic oxidation. Studies on the anodic oxidation of 2'-substituted-4- hydroxybiphenyls have established the important variables in the intramolecular reactions of olefinic centers with intermediates generated from oxidation of the aromatic moiety. A study of this reaction with other olefinic units and other solvent nucleophile combinations will be performed. A route to dienones of the type generated in these model studies would offer interesting approaches to a variety of naturally occurring dienones (e.g., Pronuciferine) and products biosynthetically derived from 2,5-cyclohexadienones. Finally, an interesting thermal route to 2,5-cyclohexadienones will be studied, making use of recently developed quinol ether anodic oxidation procedure. Since 2,5-cyclohexadienone intermediates formed via phenolic coupling reactions are the biosynthetic precursors of a wide range of natural products, a direct, mild, and efficient method for conversion of p-substituted phenols to dienones would complement existing synthetic approaches to these versatile intermediates.
