A Green, Additive-Free FeCl2-Catalyzed Microwave Platform for Acylsulfonamide Synthesis from Sodium Sulfinates and Dioxazolones in Ethanol

Abstract Acylsulfonamides are valuable carboxylic acid bioisosteres in medicinal chemistry and well applied in the pharmaceutical industry, but their preparation commonly relies on activated acyl/sulfonyl chlorides, sulfonyl azides, carbon monoxide surrogates, or stoichiometric activating reagents. Here, we report an additive-free, ligand-free, FeCl2-catalyzed microwave protocol for the synthesis of acylsulfonamides directly from bench-stable sodium organosulfinates and dioxazolones in ethanol. The method represents a distinct nitrene-transfer/S–N coupling platform that avoids precious metals, external oxidants or reductants, hazardous chlorinated reagents, and problematic polar aprotic solvents. Under microwave irradiation, diverse aryl, heteroaryl, and alkyl sulfinates are converted to acylsulfonamides within 5–15 min using only 2.5 mol % FeCl2. Most products are isolated by simple filtration, minimizing purification solvent demand and avoiding column chromatography. The utility of the protocol is demonstrated by gram-scale synthesis of the anticancer agent tasisulam and late-stage modification of pharmaceutically relevant molecules. Green chemistry metrics, including atom economy, reaction mass efficiency, optimum efficiency, and process mass intensity, reveal substantial advantages over our previously reported photocatalytic route and representative literature methods, particularly in additive economy, reaction time, scalability, and waste minimization.