Umpolung Methods with Electron Rich Aromatic Systems: Aza-ortho-Xylylenes, and N,N-Dialkylaniline N-Oxides in Synthesis

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With this award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Dr. William J. Chain of the Department of Chemistry and Biochemistry at the University of Delaware. Dr. Chain and his team of students are developing new reactions of aromatic compounds that reverse the normal behavior of these molecules. The Chain group is manipulating normally electron-rich aromatic compounds chemically such that they behave as species with low electron density. This strategy temporarily changes the reactivity of these pi-systems and triggers the formation of new carbon-carbon, carbon-oxygen, carbon-nitrogen, and carbon-sulfur bonds that are found in compounds used in industrial, medicinal, and material applications. These studies are serving to train a diverse group of graduate, undergraduate, and high school students in synthetic chemistry. The Chain group is also actively engaged in outreach activities in local elementary, middle, and high schools to promote science education and excitement towards STEM (science, technology, engineering, and mathematics) disciplines. While Friedel-Crafts reactions are well-established processes for aromatic substitution, there are still significant limitations in electron-rich settings. Professor Chain and his research group are addressing this gap in aromatic functionalization technology by developing ways to temporarily invert the reactivity of electron-rich anilines. In one approach, ortho-toluidines are being converted to aza-ortho-xylylenes (AOXs) via an electrochemical oxidation event and used as electron-acceptors for carbon-carbon bond formation. In a second approach, anilines are being oxidized to the corresponding N-oxides, which facilitates a wide array of bond formations and cyclizations that take advantage of the excision of the weak N–O bond. By virtue of the extremely mild reaction conditions associated with these new processes, the scope and application of umpolung reactions with electron rich aromatic rings is expanded thereby opening up new opportunities for organic synthesis. A better understanding of the fundamental reactivity behind these processes is also being established through collaborative computational studies. The educational plan is targeting outreach to local elementary, middle, and high schools with integration of high school students into the research program in the form of research internships.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.