(4+3) Cycloadditions of Oxidopyridinium and Oxidopyrylium Ions

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Michael Harmata of the University of Missouri-Columbia is studying a family of chemical reactions that generate seven-membered rings of carbon atoms. The transformations being investigated involve so-called [4+3]-cycloadditions, wherein a domain spanning three atoms within a reactive species containing either a nitrogen atom (oxidopyridinium ion) or an oxygen atom (oxidopyrylium ion), adds in an organized fashion to a four atom-spanning component (a diene). This research is important because it will facilitate the generation of seven-membered ring cyclic substructures that occur commonly in biologically active molecules, including natural products and pharmaceutical agents. In addition, fundamental new insights concerning issues such as molecular reactivity and bonding are likely to emerge from these studies. The broader impacts will include a high school outreach program that includes students from groups traditionally underrepresented in science, technology, engineering, and mathematics (STEM) fields and provides advanced chemistry experiences through laboratory-based summer internships. Professor Harmata will also organize an event called “Saturday Morning Science,” at which faculty from across the University of Missouri-Columbia will present their research to the general public in a manner that will excite and cultivate an interest in science among members of the community of all ages. The funded research focuses on significant further development of the [4+3]-cycloaddition chemistry of the title species with an emphasis on the identification of viable strategies to effect high levels of regio- and stereocontrol. In addition, tailoring processes to convert the complex bicyclic cycloadducts into targets of ultimate interest, including bioactive alkaloids, are likewise under investigation. In a major aim of the research, kinetic and thermodynamic effects in the cycloadditions of conjugated dienes bearing sulfur or silicon substituents will be studied for the purpose of achieving regiocontrol. In other work, functionalization of the bridgehead positions of the cycloadducts will be explored to further extend the utility of the chemistry being pursued. Finally, the conversion of the cycloadducts to cyclohepta[b]-pyrroles and cyclohepta[b]indoles will be developed. Such heterocycles are considered privileged structures as they appear in many alkaloids of biological and pharmaceutical interest. These studies build upon a substantial body of work in the PI's laboratory to define the potential for complex cyclic ring structure construction through [4+3]-cycloaddition chemistry and, as such, are expected to define more completely this interesting dimension of synthetic organic chemistry. 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.