Abstract

Despite the attractive properties of tetrafluorosulfanyl (SF4 ) compounds in drug discovery, medicinal research on SF4 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 SF4 -alkynes can serve as effective coupling partners. To overcome the challenges associated with the electron-deficient nature of SF4 -alkynes and the lability of the SF4 unit under transition-metal catalysis, an aryl radical mediated Csp -Csp 3 cross-coupling reaction is successfully developed under Cu catalysis. This methodology facilitates the coupling of SF4 -alkynes with alkyl iodides, leading to the immediate synthesis of SF4 -attached drug-like molecules. These findings highlight the potential impact of SF4 -containing molecules in the drug industry, paving the way for further research in this emerging field.

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