Synthesis of Benzo-Fused Sulfonimidate Heterocycles

Herein, we report an efficient two-step synthesis of novel benzo-fused sulfonimidate heterocycles, Benzo[<i>e</i>][1,2,3]oxathiazin-4-one-2-oxides. The first step involves the synthesis of sulfonimidate esters from <i>tert</i>-butyl <i>N</i>-sulfinyl carbamate and methyl salicylate via in situ formation of sulfonimidoyl chloride. These sulfonimidate esters undergo cyclization under acidic conditions at room temperature to afford Benzo[<i>e</i>][1,2,3]oxathiazin-4-one-2-oxide heterocycles. We also demonstrated the synthesis of both of the enantiomers of 2-(<i>p</i>-tolyl)benzo[<i>e</i>][1,2,3]oxathiazin-4-one-2-oxide from their respective enantiomerically pure sulfinyl carbamates. The reaction proceeds with inversion of configuration at the sulfur center, where (<i>S</i>)-<i>tert</i>-butyl <i>N</i>-(<i>p</i>-tolylsulfinyl) carbamate yields the corresponding R-isomer, and (<i>R</i>)-<i>tert</i>-butyl <i>N</i>-(<i>p</i>-tolylsulfinyl) carbamate affords the S-isomer. The structures of both racemic and chiral compounds were confirmed by X-ray crystallography. The practicality of the developed protocol was further demonstrated through gram-scale synthesis and mechanochemical methods. Furthermore, Benzoxathiazin-4-one-2-oxides proved to be amenable to the late-stage functionalization, expanding their synthetic utility.