Desmethyl SuFEx-IT: SO₂F₂-Free Synthesis and Evaluation as a Fluorosulfurylating Agent

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Sulfur(VI) fluoride exchange (SuFEx) click chemistry offers a powerful tool for molecular construction.
• The established solid FO2S-donor SuFEx-IT simplifies access to SuFExable compounds.
• Current preparation of SuFEx-IT requires hazardous and difficult-to-obtain sulfuryl fluoride (SO2F2).

Purpose of the Study:

• To develop a safe, scalable, and cost-effective synthesis of a desmethyl SuFEx-IT reagent.
• To provide an alternative to SO2F2-based methods for SuFEx reagent preparation.
• To demonstrate the utility of the novel reagent in synthesizing SuFExable compounds.

Main Methods:

• Development of a sulfuryl fluoride (SO2F2)-free protocol for desmethyl SuFEx-IT synthesis.
• Hectogram-scale preparation utilizing inexpensive starting materials.
• Purification-free reaction yielding the target reagent.

Main Results:

• Successful synthesis of desmethyl SuFEx-IT on a hectogram scale with 85% total yield.
• Elimination of chromatographic purification steps.
• Demonstrated utility through the synthesis of various fluorosulfates and sulfamoyl fluorides in high yields.

Conclusions:

• Desmethyl SuFEx-IT is a valuable and cost-efficient alternative to existing FO2S-donors.
• The developed protocol enables simplified and safer access to SuFEx click chemistry substrates.
• This advancement facilitates broader application of SuFEx click chemistry in various scientific fields.