Synthetic strategies toward structurally diverse seven-membered ε-sultams: a review

Seven-membered (di)benzo-ε-sultams represent an important class of cyclic sulfonamide-containing heterocycles with significant potential in medicinal chemistry and chemical biology. Recent years have witnessed substantial progress in their synthesis through organocatalytic, transition-metal-catalyzed, photochemical, electrochemical and several other approaches, enabling access to structurally diverse and enantioenriched frameworks. Key developments include asymmetric aza-Friedel-Crafts reactions, nucleophilic additions, Mannich reactions, annulation reactions and ring-expansion strategies. Despite these advances, (di)benzo-ε-sultams remain relatively underexplored, with challenges in substrate scope, three-dimensional structural complexity, and mechanistic understanding. Therefore, this review highlights the existing synthetic methodologies, mechanistic insights, stereochemical approaches, and their outcomes. It aims to inspire further research toward the synthesis of diverse ε-sultams through the development of general and sustainable strategies building on the rich chemistry of acyclic and cyclic imines.