TBHP Promotes Cross-Dehydrogenative Coupling of SF4 Alkynes with Tetrahydroisoquinolines under Copper Catalysis.

We present a viable approach for the cross-dehydrogenative coupling of Het-SF4-alkynes with tetrahydroisoquinolines under oxidative conditions, using TBHP and copper catalysts. These newly developed conditions boast enhanced yields and a more extensive range of substrates, demonstrating tolerance to various functional groups and addressing the limitations of earlier reports. Consequently, this method should increase opportunities for the exploration of SF4-containing compounds and their potential applications in drug discovery, materials science, and as alternatives to PFAS.

Cross Dehydrogenative Coupling of SF4-Alkyne with Tetrahydroisoquinolines.

This study introduces a dual-catalytic method for cross-dehydrogenative coupling (CDC) between tetrahydroisoquinolines and Py-SF4-alkyne using visible-light photoredox catalysis. This protocol enables selective C(sp3)-H alkynylation, expanding the synthetic toolkit for SF4-based molecules. Demonstrating efficiency and substrate versatility, this approach opens new avenues in hexacoordinated tetrafluorinated sulfur chemistry and CDC strategies and holds significant promise for drug discovery and materials science.

Expanding the Frontier of Linear Drug Design: Cu-Catalyzed Csp -Csp 3 -Coupling of Electron-Deficient SF4 -Alkynes with Alkyl Iodides.

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.