Project Grant R01GM158873

The National Institute of General Medical Sciences awarded the Trustees of Indiana University $340,016 on August 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop innovative single-electron radical chemistry methods for medicinal synthesis.

The funded research advances synthetic methods to build complex, three-dimensional small molecules containing fluorine and other functional groups that improve drug performance. Traditional cross-coupling reactions using expensive noble-metal catalysts excel at forming flat structures but struggle with bonds at sp3 carbons, limiting structural diversity of drug candidates. This project addresses that gap by developing single-electron strategies catalyzed by abundant base metals—iron, manganese, and copper—to directly transform common functional groups such as alcohols, alkenes, alkyl halides, and C-H bonds into previously difficult-to-make bonds.

The work pursues three specific aims: creating direct methods to install fluorinated carbon motifs at sp3 positions from simple precursors; developing new reactions to form alkyl boronic esters through borylation from alkenes, halides, or alcohols, including asymmetric variants; and enabling practical introduction of the pentafluorosulfanyl group via radical difunctionalization of alkenes and through novel transfer reagents. The expected outcome is a set of robust methodologies that expand the medicinal chemistry toolkit, accelerate synthesis of structurally diverse sp3-rich molecules, and shorten the path to new therapeutics.

Performance occurs in Bloomington, Indiana, with a period of performance through July 31, 2030.