RUI: Further Expansion of Sulfone Iminium Reagents and Their Use in Fluorination and Cyanation Methodologies

Bryn Mawr College, Bryn Mawr PA

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Patrick Melvin of Bryn Mawr College is studying the development of highly reactive molecules capable of introducing a fluorine atom into various compounds. Fluorine, an element on the periodic table, has risen in prominence over the last several decades, largely due to a host of beneficial properties that it can impart on organic molecules. This has led to fluorine atoms being introduced to many of the leading pharmaceuticals on the market, often improving the activity of existing drugs while also paving the way for new therapeutics. Given these important enhancements, the Melvin laboratory has devised a new class of reagents, called sulfone iminium fluorides (SIFs), which are capable of incorporating fluorine in the most efficient and expedient ways possible. Research plans here aim to expand the utility of SIFs to tackle even more challenging fluorination reactions, such as the formation of critical phosphorus – fluorine bonds. Additionally, Dr. Melvin is investigating how this reagent class can be altered to not only improve fluorination reactions, but to also enhance the creation of nitriles, a much sought-after functional group on medicinally relevant organic molecules. Beyond the laboratory, Dr. Melvin is bringing his research on sulfone iminium fluorides to the classroom in an upper-level, research-inspired laboratory course at Bryn Mawr College. Finally, to increase chemistry engagement amongst the all-female undergraduate population, Dr. Melvin is developing a week-long “Nobel Prize-winning Chemistry Tutorial”, which offers students a chance to actively connect with current, cutting-edge science. In this research, Patrick Melvin of Bryn Mawr College is further probing the influence of sulfone iminium fluorides (SIFs) on various organic methodologies. Recently, the Melvin laboratory has developed a highly reactive class of SIFs and demonstrated their remarkable propensity for the deoxyfluorination of alcohol and carboxylic acids and their engagement in sulfur fluoride exchange (SuFEx) chemistry. The enhanced reactivity of SIFs leads to rapid and efficient transformations for reactions that have traditionally been challenging and slow. Using these reagents, the Melvin laboratory is investigating their effectiveness on the synthesis of heteroatom – fluorine bonds, namely phosphorus-fluorine and sulfur-fluorine bonds, which have a growing importance in both medicinal and synthetic chemistry. Furthermore, classic deoxyfluorination reactions of carbonyl functional groups will be examined using these reagents with an eye toward circumventing the need for reactive fluoride sources. Efforts are ongoing to modify the SIF structure to enable external base-free deoxyfluorination reactions, which would further elevate the utility of this methodology. Finally, the Melvin laboratory is exploring more extensive alterations to the sulfone iminium core structure to employ this reagent class in cyanation reactions via nucleophilic and electrophilic pathways. This research demonstrates that fluorination methodologies can be significantly improved through careful reagent design and shows real promise for developing new pathways to the installation of important organic functionality; most notably via the crafting of C-F and C-CN bonds. 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.