| Our group is interested in the study and use of radical cation intermediates formed by anodic oxidation of electron rich olefins. When the radical cation intermediate contains an intramolecular nucleophile, the nucleophile can trap the radical cation resulting in a cyclization reaction. The anodic oxidation can reverse the polarity of functional groups and therefore can cause umpolung reactions. These reactions allow unusual synthetic disconnections to be used, thus increasing the synthetic options available.;Our group previously demonstrated that a hydroxyl group can trap a radical cation, formed by anodically oxidizing a ketene dithioacetal, to form a cyclic ether. By using an tertiary amide as the trapping group, a five-member lactone may be formed. These reactions can be used to stereoselectively form a tetrasubstituted center. We have found that the addition of water to the electrolysis reaction increases the yield of the lactone. This yield increase is apparently due to the water hydrolyzing the imminium ion, which is initially formed, to the desired product before the imminium ion can undergo undesired side reactions.;To test the stereoselectivity of this cyclization, we targeted the synthesis of (+)-crobarbatic acid. An enantiopure amide ketene dithioacetal was synthesized. Upon electrolysis, this substrate yielded a single isomer. However, this isomer is epimeric with the configuration required for crobarbatic acid.;To obtain the desired stereochemistry, we are synthesizing an electrolysis substrate which contains functional groups that are compatible with the electrolysis reaction and can be transformed to the final product after the electrolysis reaction sets the configuration of the lactone ring's tetrasubstituted center. One of these transformations is the conversion of the methoxy dithioacetal group, formed by one end of the ketene dithioacetal group during electrolysis, to a methyl group. Exploration of this transformation has shown that the methoxy dithioacetal functional group potentially has rich synthetic applications. |
