Synthesis of Tropones from Arenes for Complex Molecule Synthesis

With the support of the Chemical Synthesis program in the Division of Chemistry, Professor Richmond Sarpong of the University of California–Berkeley will study the conversion of one group of compounds that contain a six-membered benzene ring to another group of compounds that contain a seven-membered ring (tropone). This ring expansion protocol will connect two families of compounds that are found in a range of agrochemically and medicinally relevant compounds. The work will expand the scope of seven-membered ring containing compounds in the tropone family and will also provide a platform for training researchers in the practice of multi-step chemical synthesis which will prepare them for positions in the pharmaceutical and agrochemical industries. This work will provide valuable training to a diverse group of graduate students for careers in STEM. The PI is also actively involved in outreach activities in the local community. The goal of the proposed project is to develop a two-step sequence for the conversion of phenols to tropones. Specifically, the intellectual advance is to convert phenols to para-quinols using an oxidative dearomatization reaction. The resulting para-quinols will then be engaged with diazo compounds to effect a net one carbon insertion/ring expansion through what is known as a Büchner–Curtius–Schlotterbeck reaction. A range of Lewis acids and diazo compounds will be investigated to identify reagents and conditions that lead to the highest selectivities and yields. Mechanistic and computational studies will be conducted to gain insight into the selectivity-determining factors so that a broad range of highly selective reactions can be achieved. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.