Development and Characterization of Anomalous Cationic Cyclizations and Rearrangements

About This Grant

With the support of the Chemical Synthesis Program of the Division of Chemistry, Professor Alison Frontier of the Department of Chemistry at the University of Rochester is studying anomalous forms of known cyclization reactions. Some of the reactions chosen for exploration in this project lie at the interface between two well-defined reaction classes that are understood by the community to operate according to different sets of rules. These rules are not well understood. A central goal of the program is to learn more about these ambiguous, underexplored reactions, and understand the behavior of systems designed to occur at the “edges” of an accepted paradigm of reactivity. Other anomalous reactions slated for investigation are expected to enable the Frontier lab to build three-dimensional molecules with unique spatial arrays of carbon, nitrogen and oxygen atoms. These structural features are critical to the behavior of small molecules, and new arrays could uncover new possibilities for chemical reactivity or biological activity. The research conducted by Professor Frontier and her students will expand the range of three-dimensional molecules that can be assembled using chemical methods. Professor Frontier also continues to develop and maintain the “Not Voodoo” website, an educational resource she created in 2004. The site is designed to help students demystify laboratory protocols and procedures. It serves hundreds of organic experimental chemists each day, from students just beginning independent research, to advanced students looking for tips or tricks. In this program, all three research projects focus on anomalous versions of otherwise well understood reactions. The first two projects will explore reactions at the edges of known electrocyclic chemistry. In project 1, the team will explore the interface between electrocyclic and ionic reactivity, seeking to characterize a large group of pentannulation reactions of ambiguous classification. The examples have been collected over many years, comprising cases from the PI’s work and others that stand out as atypical and potentially misclassified. In project 2, the team aims to extend the boundaries of electrocyclic reactivity by developing synthetically useful higher-order cationic electrocyclizations and evaluating both periselectivity and degree of pericyclicity. The findings from projects 1 and 2 will establish parameters for classifying cyclization reactions, which can be applied by members of the community to characterize a new or existing reaction. In project 3, Professor Frontier and coworkers will develop nonlinear polyene cyclizations for the synthesis of highly functionalized, topologically complex heterocycles. When the p-orbital systems of polyene reactants are arranged in a nonlinear fashion, and cationic chemistry is initiated, a combination of cyclization and [1,2]-rearrangement processes can ensue. Through experimentation and analysis, the lab will learn to control these nonlinear cascades. Professor Frontier will also execute expansions and improvements within the Not Voodoo website she created in 2004. Activities will include routine maintenance, compiling case studies that highlight problem-solving strategies used by experts, updating and reorganizing existing content, and adding new technical content. 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.