One-Pot Silylation–Amination Synthesis of 3- N -Substituted Benzo[ d ]isothiazole 1,1-Dioxides

High Resolution Image Download MS PowerPoint Slide An alternative silylation–amination route for the synthesis of 3- N -substituted benzo[ d ]isothiazole 1,1-dioxides is presented. These saccharin-based scaffolds have attracted increasing interest in medicinal chemistry, particularly as potential modulators of hypoxia-inducible factor-2. The preparation of such structures is often associated with chlorination–amination approaches, which suffer from operational drawbacks, the use of chlorinating reagents, and variable efficiency. Herein, we report a one-pot silylation–amination protocol employing hexamethyldisilazane as the silylating agent. The method is operationally simple, applicable to a broad substrate scope, and affords the desired products in moderate to excellent yields (31–99%) under solvent-free conditions.