Basicity-Tuned Reactivity: diaza-[1,2]-Wittig versus diaza-[1,3]-Wittig Rearrangements of 3,4-Dihydro‑2H‑1,2,3-benzothiadiazine 1,1-Dioxides

The base-induced (t-BuOK) rearrangement reactions of 3,4-dihydro-2H-1,2,3-benzothiadiazine 1,1-dioxides result in a ring opening along the N–N bond, followed by ring closure with the formation of new C–N bonds. The position of the newly formed C–N bond can selectively be tuned by the amount of the base, providing access to new, pharmacologically interesting ring systems with high yield. While with 2 equiv of t-BuOK 1,2-benzisothiazoles can be obtained in a diaza-[1,2]-Wittig reaction, with 6 equiv of the base 1,2-benzothiazine 1,1-dioxides can be prepared in most cases as the main product, in a diaza-[1,3]-Wittig reaction. DFT calculations and detailed NMR studies clarified the mechanism, with a mono- or dianionic key intermediate, depending on the amount of the reactant base. Also, the role of an enamide intermediate formed during the workup of the highly basic (6 equiv of base) reaction was clarified. The substrate scope of the reaction was also explored in detail.