Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, Germany.
Department of Process Research and Development, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey, 07065, USA.
Angew Chem Int Ed Engl. 2021 Mar 1;60(10):5056-5062. doi: 10.1002/anie.202016164. Epub 2021 Feb 2.
Sulfonamides are among the most important chemical motifs in pharmaceuticals and agrochemicals. However, there is no methodology to directly introduce the sulfonamide group to a non-prefunctionalized aromatic compound. Herein, we present the first dehydrogenative electrochemical sulfonamide synthesis protocol by exploiting the inherent reactivity of (hetero)arenes in a highly convergent reaction with SO and amines via amidosulfinate intermediate. The amidosulfinate serves a dual role as reactant and supporting electrolyte. Direct anodic oxidation of the aromatic compound triggers the reaction, followed by nucleophilic attack of the amidosulfinate. Boron-doped diamond (BDD) electrodes and a HFIP-MeCN solvent mixture enable selective formation of the sulfonamides. In total, 36 examples are demonstrated with yields up to 85 %.
磺胺类药物是医药和农用化学品中最重要的化学结构之一。然而，目前还没有将磺胺基团直接引入未经官能化的芳族化合物的方法。在此，我们通过利用（杂）芳环的固有反应性，通过亚氨基磺酸盐中间体与 SO 和胺进行高度收敛的反应，提出了第一个脱氢电化学磺胺合成方案。亚氨基磺酸盐既是反应物又是支持电解质。芳族化合物的直接阳极氧化引发反应，随后亚氨基磺酸盐进行亲核攻击。掺硼金刚石（BDD）电极和 HFIP-MeCN 溶剂混合物可实现磺胺类化合物的选择性形成。总共展示了 36 个实例，产率高达 85%。
