Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
School of Pharmacy, Gannan Medical University, 1 Yixueyuan Road, Ganzhou 341000, China.
Chem Commun (Camb). 2020 Mar 19;56(23):3437-3440. doi: 10.1039/d0cc00721h.
Nitroarenes are used as the coupling partners in the preparation of sulfonamides via the insertion of sulfur dioxide. A three-component reaction of arylboronic acids, nitroarenes, and potassium metabisulfite under copper catalysis proceeds smoothly, giving rise to a range of sulfonamides in good to excellent yields with broad substrate scope. Various functional groups including hydroxyl, cyano, amino, and carbonyl are all tolerated. A plausible mechanism is proposed, showing that arylsulfinate is the intermediate and the copper-assisted interaction of the nitroarene and arylsulfinate is the key step. This approach is also extended to the late-stage modification of a currently marketed drug (flutamide).
硝芳烃被用作通过二氧化硫插入来制备磺胺类药物的偶联伙伴。在铜催化下,芳基硼酸、硝芳烃和重亚硫酸钾进行三组分反应,顺利进行,得到一系列具有广泛底物范围的磺胺类化合物,产率良好至优秀。各种官能团,包括羟基、氰基、氨基和羰基,都可以耐受。提出了一种合理的机制,表明芳基亚磺酸盐是中间体,并且硝芳烃和芳基亚磺酸盐的铜辅助相互作用是关键步骤。该方法还扩展到目前市售药物(氟他胺)的后期修饰。