Radical perfluoroalkylation reactions mediated by halogen-bonding photocatalysis

The addition of different perfluoroalkyl moieties to organic compounds is a frequently investigated method in medicinal chemistry due to their superior solubility, metabolic stability, and bioavailability over their non-fluorinated equivalents. Radical perfluoroalkylation processes provide a milder approach to accessing these compounds. We envisioned that the C–X bond of perfluoroalkyl halides might be directly activated by a halogen-bonding interaction, which would then lead to the formation of an electron donor-acceptor complex (EDA complex) which can be excited with visible light irradiation. We have demonstrated radical perfluoroalkylation reactions where substituted hydroquinones catalytically engage perfluoroalkyl iodides through a halogen-bonding interaction to promote these transformations under visible light irradiation. Our progress on expanding the reaction scope to silyl enol ethers for the α-perfluoroalkylation of ketones will also be presented. While we have successfully demonstrated this reactivity with perfluoroalkyl iodides, it would be highly beneficial to extend this reactivity to perfluoroalkyl bromides, as these substrates are more readily available commercially and intrinsically more bench-stable than their iodide counterparts. While doing so, we ran into the challenge of C–Br bonds being weaker halogen bond acceptors compared to C–I bonds. Thus, we hypothesized that a more general and robust method would be a Finkelstein substitution of perfluoroalkyl bromides to generate the more reactive perfluoroalkyl iodides in situ. Our progress in implementing this catalytic Finkelstein approach to access perfluoroalkyl bromides via halogen-bonding photocatalysis will be presented. Finally, the substituted hydroquinone catalyst that we used throughout these studies have a few limitations. Our initial results in developing novel second-generation halogen-bonding photocatalysts which would overcome the drawbacks from the first-generation catalysts will be discussed.