An Efficient Method for the Synthesis of Benzofused Five-Membered Cyclic Sulfamates

An efficient and scalable method for the synthesis of 1,2,3-benzoxathiazole 2,2-dioxides and related five-membered cyclic sulfamates employing gaseous sulfuryl fluoride (SO2F2) in the presence of Et3N is described. The one-pot cyclization of 2-aminophenol derivatives proceeds at rt and tolerates a variety of substituents on the aromatic ring, including electron-withdrawing groups, as well as N-substituted substrates. The method provides the target heterocycles in improved yields compared to classical SO2Cl2-based protocols and is readily scalable to 50 g without loss of efficiency. A virtual library of 49 cyclic sulfamate derivatives was generated and evaluated using the LLAMA approach. The library members exhibit favorable lead-like physicochemical profiles, with 100% compliance with the Lipinski, Veber, Muegge, and GSK 4/400 filters, supporting the utility of the proposed chemotypes for medicinal chemistry applications.