Research Projects

The proposal aims to develop synthetic strategies for selective C-F bond formation reactions using visible light and electricity as energy sources. This can be used to late-stage functionalize drug molecules and introduce new fluorine-containing pharmacophores. Fluorine's electronegativity, size, omniphobicity, lipophilicity, electrostatic interactions, and strong bond with carbon can significantly change the chemical/stereochemical outcome in an organic molecule. About one-third of top-performing drugs contain fluorine atoms in their structure. Selective fluorination in any drug molecule can improve its purposeful performance by impeding oxidative metabolism and improving bioabsorption and pharmacokinetics. Despite its socio-economical impact, there is a gap between the needs of the pharmaceutical industry and the current methodological efficiency of fluorine chemistry. The proposal proposes late-stage fluorination reactions using cheap and abundant electrophilic and nucleophilic fluorine sources. A dual photoredox/HAT catalytic process is hypothesized to provide exceptional reactivity in introducing a fluorine atom in place of hydrogen. A designed N-ammonium ylide salt as a potential HAT catalyst will precisely activate an electron-rich C-H bond via polarity-matching. A diverse range of electrophilic fluorinating sources can be employed. The proposal also aims to take advantage of electrochemical organic synthesis for late-stage diversification of bioactive molecules and pharmacophores by disallowing stoichiometric reagents in a green and sustainable way.