Renzhe, Li, Chang, Liu, Chao, Hu, Jet, Tsien, Michael, Hayes, Si-Jie, Chen, Kanda, Yuzuru, Rohan, R. Merchant, Bryan, Matsuura and Tian, Qin (2025) Bench-stable reagents for modular access to persulfuranyl scaffolds. Nature communications, 16. pp. 10185-10192. ISSN 2041-1723

Abstract

The vast expanse of chemical space offers limitless possibilities for medicinal chemists, particularly in discovering novel scaffolds and functional groups with drug-like properties. However, the widespread adoption of these functional groups is often initially limited by their synthetic accessibility and functionalization. Among these functional groups, the pentafluorosulfanyl group is long considered a possible (bio)isostere for tert-butyl and trifluoromethyl groups, but is synthetically challenging to access due to limited chemical reagents and methodologies. To bridge this gap, we have developed a general pentafluorosulfanylation platform that employs bench-stable solid reagents to generate SF₅ radicals via a decarboxylation and β-scission sequence. This strategy enables a variety of operationally simple transformations, expanding the accessibility of SF₅-containing molecules. Notably, this reagent design is also adaptable to other persulfuranyl groups, such as trifluoromethyl tetrafluorosulfanyl and aryl tetrafluorosulfanyl groups. Taken together, generating an armamentarium of these stable reagents and practitioner-friendly chemical methodologies will enable the synthesis of challenging and biologically relevant sulfur(VI) chemical scaffolds in an expedient manner.

Item Type:	Article
Date Deposited:	03 Dec 2025 00:45
Last Modified:	03 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/56974