Expanding the Frontier of Linear Drug Design: Cu-Catalyzed C sp -C sp 3 -Coupling of Electron-Deficient SF 4 -Alkynes with Alkyl Iodides.

Despite the attractive properties of tetrafluorosulfanyl (SF 4 ) compounds in drug discovery, medicinal research on SF 4 molecules is hindered by the scarcity of suitable synthetic methodologies. Drawing inspiration from the well-established Sonogashira cross-coupling of terminal alkynes under Pd-catalysis, it is envisioned that SF 4 -alkynes can serve as effective coupling partners. To overcome the challenges associated with the electron-deficient nature of SF 4 -alkynes and the lability of the SF 4 unit under transition-metal catalysis, an aryl radical mediated C sp -C sp 3 cross-coupling reaction is successfully developed under Cu catalysis. This methodology facilitates the coupling of SF 4 -alkynes with alkyl iodides, leading to the immediate synthesis of SF 4 -attached drug-like molecules. These findings highlight the potential impact of SF 4 -containing molecules in the drug industry, paving the way for further research in this emerging field.