Tunable Skeletal Editing of Benzothiazole and Benzisothiazole Via Carbene Transfer Reactions.

Understanding how carbene reactivity is modulated by both the heteroarene scaffold and activation mode is critical for advancing selective functionalization strategies. Herein, we report a comparative study revealing the divergent reactivity of benzothiazole and benzisothiazole under both photochemical and metal-catalyzed carbene transfer conditions. Under photochemical conditions, free carbenes induce a stepwise transformation of benzothiazole involving initial carbon-atom exchange followed by carbon atom insertion, affording benzothiazoline and benzothiazine derivatives. In contrast, benzisothiazole undergoes direct monocarbon atom insertion, selectively forming ring-expanded products. Notably, metal-catalyzed carbene transfer does not proceed with aromatic benzothiazole but can efficiently engage its dearomatized intermediate through carbon atom insertion, enabling access to the same ring-expanded benzothiazine scaffolds with an expanded substrate scope. Mechanistic studies, including control experiments, isotope labeling, and DFT calculations, support the proposed pathways and clarify how scaffolds govern the distinct reactivity patterns. These findings highlight the complementary reactivity profiles of free and metal-bound carbenes and establish a structure- and activation-mode-guided platform for the selective functionalization of heteroaromatic systems.