Manganese-Catalyzed Sulfonamidation of (Hetero)Aromatic C-H Bonds Using Direct Primary Sulfonamides: En Route to Late-Stage Diversified Sulfonamide Drugs.

We herein report a novel manganese-catalyzed C(sp2)-H sulfonamidation of arenes and heteroarenes using primary sulfonamides directly. This protocol employs amide-oxazoline and 8-aminoquinoline as directing groups, operates without stringent inert conditions, and proceeds efficiently under air. To the best of our knowledge, this is the earliest report of using a catalytic metal salt for amide-oxazoline- or 8-aminoquinoline-directed C(sp2)-H sulfonamidation. This newly developed protocol affords the desired N-(hetero)aryl secondary sulfonamides in good to excellent yields, demonstrating a broad substrate scope and remarkable tolerance toward a wide range of functional groups, including heterocycles. This method has been successfully applied to a variety of commercially available primary sulfonamide drugs, thereby highlighting its potential for late-stage diversification in drug discovery. The protocol has been successfully implemented at the gram scale and applied to downstream product derivatization, underscoring its practical synthetic utility. Moreover, the employed directing groups can be readily removed from the products, efficiently yielding 2-sulfonamide-substituted aromatic acid derivatives. Consequently, we further demonstrated the utility of this protocol by applying it to telmisartan, a drug bearing an aromatic carboxylic acid moiety, to achieve late-stage C(sp2)-H sulfonamidation.