Benzene-1,3-disulfonyl fluoride and Benzene-1,3,5-trisulfonyl fluoride: Low-Cost, Stable, and Selective Reagents for SuFEx-Driven Deoxyazidation

The development of synthetic methods for the synthesis of organic azides is highly important, given their critical role in advancing click chemistry over the last twenty years. We report a reagent-economical, reliable, and scalable synthesis of alkyl azides from primary and secondary alcohols. This robust click method capitalizes on the synergistic interaction between Sulfur Fluoride Exchange (SuFEx) reagents – specifically, benzene-1,3-disulfonyl fluoride (BDSF) or benzene-1,3,5-trisulfonyl fluoride (BTSF) – and trimethylsilyl azide (TMSN₃). The method offers procedural ease, accommodates a wide array of substrates, and enables late-stage functionalization. Additionally, we demonstrate the protocol‘s adaptability by validating a straightforward one-pot deoxyazidation-CuAAC sequence for drug discovery applications.