Oxidative Strategies for the Synthesis of N-Alkyl and N-Aryl Pyridinium Salts

Temple University, Philadelphia PA

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Sarah Wengryniuk of Temple University is studying new approaches for the preparation of an important class of chemical substances called N-alkyl and N-aryl pyridinium salts. These positively charged, nitrogen-containing compounds are involved in cellular processes, found in a variety of useful functional materials, and they can be used as antimicrobial agents in products such as mouthwash. Furthermore, pyridinium salts serve as valuable precursors to subunits that commonly occur in active pharmaceutical ingredients. The funded project will focus on the development of new methods to generate pyridinium salts using environmentally benign processes, including the use of non-toxic iodine-based oxidants and electrochemical methods. The chosen approaches will allow for access to a more diverse range of pyridinium salts than was previously possible, facilitating the manufacture of pharmaceuticals, and their study will also help to advance emerging technologies for chemical synthesis. The broader impacts of the award will extend to enabling Professor Wengryniuk to continue her significant efforts to advance the mentorship and promotion of women in science, technology, engineering, and mathematics (STEM). Specifically, under the auspices of the previously established Outstanding Women Leaders in Science (OWLS) initiative, the PI will develop a female mentor/female mentee match program and establish an annual Women in Chemistry seminar series at Temple University to provide scientific and professional mentorship opportunities for female students. The synthesis of N-alkyl and N-aryl pyridinium salts will be investigated by two strategies that offer unrivalled versatility as compared to earlier approaches by virtue of their reactivity umpolung. The first aim will build upon the PI's established research program in the area of nitrogen-ligated iodine(III) reagents, with the development of heterocyclic group transfer reactions for a metal-free oxidative functionalization of alkenes and arene C–H bonds. The second aim complements the first in both reagent platform and target scaffolds. Thus, through the use of electrochemical oxidation, radical cation intermediates will be leveraged as a means of synthesizing 2,4,6-trisubstituted pyridinium salts via C–H amination, providing new points of entry to emerging cross coupling handles. Throughout, the overarching goal of the funded project is to provide innovative and enabling methods to access N-alkyl and N-aryl pyridinium salts by oxidative strategies. Success in these endeavors will not only provide access to diverse scaffolds for azacycle synthesis and radical cross couplings, but also advance both nitrogen-ligated hypervalent iodine reagent chemistry and electrochemistry-based synthetic methods. 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.