Rare Earth Catalyzed Redox‐Neutral (4+1) Annulations Between Ortho ‐Aminobenzenesulfonamides and Aldehydes

Abstract Herein, we report the development of rare earth catalyzed efficient and scalable synthesis of medicinally relevant 3,4‐dihydro‐2 H ‐1,2,4‐benzothiadiazine‐1,1‐dioxides by redox‐neutral (4 + 1) annulation between ortho ‐aminobenzenesulfonamides and aldehydes. The reactions, under mild conditions, demonstrate excellent yields (up to 97%) with a broad range of substrates encompassing alkyl, alkenyl, alkynyl, and aryl aldehydes. Notably, Er(OTf) 3 and a chiral PyBox ligand S are identified as the most effective combination to provide high enantioselectivity up to 82% ee. In addition, four bioactive molecules are synthesized, including clinically widely prescribed Ethiazide, Cyclothiazide, and Thiabutazide.