Optimization of One-Pot Coupling Reactions of Di-Substituted Furans for Disease Treatment
Dr. Don L. Warner
The core of many types of natural products and pharmaceuticals contain aryl structures, and efficient methods of synthesizing these compounds are crucial to the work of many organic chemists. A palladium catalyzed carbon-carbon bond forming process known as the Suzuki-Miyaura cross-coupling reaction (SMC) is often a popular choice for synthesizing these compounds. The SMC has many advantages over other methods, including high stability and commercial availability of its reagents, mild conditions, high tolerance toward functional groups, and ease of separating byproducts. The furan is a specific aryl group often seen in pharmaceuticals that can be functionalized using the SMC. In this research, we sought to optimize the one-pot coupling of di-brominated furans to create differentially tri-substituted furan products. To start, we investigated the first coupling step and found that favorable reaction conditions used palladium acetate, a boronic acid, and sodium carbonate (base) in a 1:1 water, DMF solution. These conditions were then adopted into a one-pot bis-coupling reaction that couples the furan twice, versus the mono-coupling that is often done in SMC's. This one-pot reaction is regioselective, producing a specific bis-coupled furan. With this reaction in place, future work involves synthesizing furans with different functional groups to assess functional group tolerability and to continue to improve yield. Having this reaction at their disposal, organic chemists should more easily synthesize small molecules for medicinal purposes.
LaMay, Jacob; Dickerson, Elsie; Feci, Andrea; Winkler, Emily; Tuccinardi, Joseph; Reeves, Ryan; and Warner, Don L., "Optimization of One-Pot Coupling Reactions of Di-Substituted Furans for Disease Treatment" (2021). 2021 Undergraduate Research Showcase. 90.