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Bench-stable reagents for modular access to persulfuranyl scaffolds

Renzhe Li, Chang Liu, Chao Hu, Jet Tsien, Michael Hayes, Si-Jie Chen, Yuzuru Kanda, Rohan R. Merchant, Bryan S. Matsuura, Tian Qin

2025Nature Communications7 citationsDOIOpen Access PDF

Abstract

Pentafluorosulfanyl group has been long considered a potential (bio)isostere for tert-butyl and trifluoromethyl groups, yet limitations in methodologies have constrained access to it. 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 a collection of these stable reagents and practitioner-friendly chemical methodologies enables the synthesis of challenging and biologically relevant sulfur(VI) chemical entities in an expedient manner. The pentafluorosulfanyl group has been long considered a potential (bio)isostere for tert-butyl and trifluoromethyl groups, yet limitations in methodologies have constrained access to it. Here, the authors report a general pentafluorosulfanylation platform that employs bench-stable solid reagents to generate SF5 radicals via a decarboxylation and β-scission sequence.

Topics & Concepts

ReagentModular designTrifluoromethylComputer scienceDecarboxylationCombinatorial chemistryArylBridge (graph theory)TrifluoromethylationRetrosynthetic analysisChemistryVariety (cybernetics)Simple (philosophy)NanotechnologyFunction (biology)Drug discoveryFluorine in Organic ChemistryRadical Photochemical ReactionsSulfur-Based Synthesis Techniques
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