Fluorothiazynes as SuFEx Ambiphiles: Interconversion to Aminosulfurdiimidoyl Fluorides

Sulfur(VI) functional groups are ubiquitous in medicinal chemistry, valued for their stability and ability to modulate molecular properties. While sulfonamides, sulfones, and sulfates dominate existing drug scaffolds, more complex, multidirectional sulfur(VI) cores remain underexplored. Here, we show a viable route from amino difluorothiazynes to aminosulfurdiimidoyl fluorides (ASDFs), via sequential alkylation and imination. Leveraging the ambiphilic character of fluorothiazynes—acting as both N-nucleophile and S-electrophile—we generate thiazynium intermediates that, upon trapping with primary amides or sulfonamides, afford ASDFs in good yields. The further transformability of the products as SuFEx electrophiles is demonstrated, notably a sulfurdiimidamide derivative that is likely the first unsymmetrically substituted tetraimidosulfur species. This work expands the toolkit of azasulfur(VI) fluorides, introducing the first general route to ASDFs as stable, functionally diverse platforms for further chemical diversification.