Expanding the Frontier of Linear Drug Design: Cu‐Catalyzed C_sp–C_sp³‐Coupling of Electron‐Deficient SF₄‐Alkynes with Alkyl Iodides

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 C_sp–C_sp³ 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.