Author: Mark Maust
Approved: Spring 2019
Palladium-catalyzed olefin difunctionalizations have been used extensively in the organic synthesis field for numerous molecular transformations. Often, these transformations include the formation of carbon-carbon bonds that are used in the synthesis of many biologically active compounds, such as pharmaceuticals. Previous research investigated a palladium-catalyzed olefin difunctionalization that forms a new C-O bond and a C-C bond. Varying electronic conditions of the aromatic ring causes the reaction to diverge between two products, tricyclic and α,β-unsaturated. Reaction divergences occurs at the C-C bond forming step following standard electrophilic aromatic substitution patterns. Through optimizing the formation of the α,β-unsaturated product a third product, the α-hydroxy product, was discovered. In the presence of water, the α-hydroxy product is favored through an SN1-like mechanism with water being the nucleophile to outcompete β-hydride elimination that would form the α,β-unsaturated product. Investigation of the formation of the α-hydroxy product revealed a fourth product, the terminal hydroxy product, where water can compete with the electrophilic aromatic substitution reaction when aromatic rings are weakly activated. Understanding the limitations and scope of these reactions gives them potential to be used more frequently in complex syntheses.