Unlocking DAST‐Type Reagents for Modular Synthesis of Sulfur‐Containing Motifs

Abstract Multi‐heteroatom‐substituted sulfur centers are increasingly significant in drug discovery, yet their modular synthesis remains challenging. Current strategies employing sulfinylamines, sulfurdiimides, or SOF 4 suffer from inherent limitations. To address this, a general and practical strategy for constructing diverse sulfur centers bearing multiple oxygen or nitrogen substituents is urgently needed. Herein, we report a modular synthesis of such motifs using commercially available DAST‐type reagents as underexplored sulfur precursors. This methodology expands the utility of classical fluorination agents as sulfur sources, operates under ambient and mild conditions, and enables rapid access to diverse S(IV) and S(VI) architectures through sequential substitution and further flexible transformations. The practicality of this approach is highlighted by late‐stage functionalization of bioactive molecules and gram‐scale synthesis. Mechanistic studies support the proposed highly reactive S(IV)‐F intermediate.