Faculty Sponsor's Department(s):
Cyclopentenone scaffolds are prevalent in a wide range of biologically active compounds such as (-)-cephalotaxine (an antiviral & antitumor agent) and stemonamine (the basis for a respiratory drug). Cyclopentenones are synthesized through the aza-Piancatelli rearrangement of furylcarbinols. Previous research on the synthesis of cyclopentenones includes the ability to control the relative stereochemistry in the product. To further improve this work, we would like to successfully control the absolute stereochemistry. There are only a few published papers that demonstrate this rearrangement asymmetrically. Our research helps to fill this gap by designing a method that gives us the ability to control absolute stereochemistry by controlling the direction of the conrotatory 4π electrocyclic ring closure. Research shows that chiral acid catalysts are efficient in asymmetric rearrangements. A paper published by Lambert et al. inspired us to use their Brønsted acid catalyst. Various reaction conditions such as solvent, temperature, and catalyst loading were screened and optimized conditions were found. My research further expands the substrate scope by evaluating both major reactants (the furylcarbinol and the aniline). We have developed one of the few asymmetric Aza-Piancatelli reactions using a Bronsted acid to catalyze the reaction. Our optimized conditions provide good yields and control over enantio-selectivity, allowing us to optimize our substrate scope to include various amine nucleophiles as well as varying carbinols. The study will have important implications for the synthesis of compounds containing a cyclopentenone scaffold.