One of the synthetic challenges in chemistry is the development of catalysts that selectively activate C-H bonds. In this regard, allylic C-H bonds represent a useful motif that can be selectively activated using catalytic palladium salts. Unfortunately, methods for the allylic C-H activation of terminal olefins often suffer from drawbacks, which include long reaction times, high catalyst loadings, and low regioselectivities, resulting in a complex mixture of oxidized products. Several years ago, we discovered that a catalyst system comprised of palladium salts and a novel thioether ligand promoted the allylic oxidation of terminal olefins to selectively afford linear allylic acetates. This novel catalyst system was found to promote the reaction at a significantly faster rate and with lower catalyst loadings than previously reported methods.
One of the limitations of our novel catalyst system was that disubstituted olefins were slow to react, producing only trace amounts of products at elevated temperatures. Following these results, we soon discovered that cis-vinylsilanes were highly reactive for allylic oxidations. Fortunately, we found that these reactions proceed with low catalyst loadings and provide the allylic acetate products with complete regioselective control. Additionally, we discovered an oxidant-controlled protocol to afford the branched allylic acetates with diastereoselective formation of either the cis- or trans-vinylsilanes. The kinetic differences between the oxidant systems are believed to be the controlling factor for the diastereoselectivity of the reactions.
Palladium-catalyzed allylic C-H oxidations of terminal olefins do not typically proceed with alcohol or amine nucleophiles, due to competing Wacker-type oxidations. Interestingly, we discovered that the allylic oxidations of cis-vinylsilanes could be expanded to include allylic etherification and amination processes. Although the intermolecular allylic etherifications fail to provide significant amounts of the oxidized products, the intramolecular etherification process proceeds smoothly to provide oxygen heterocycles. The analogous intramolecular amination reactions were recently discovered and efforts are currently underway to further this chemistry.