Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Lu, Hefei, 230026, China.
State Key Laboratory of Bioorganic & Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2022 Oct 24;61(43):e202210483. doi: 10.1002/anie.202210483. Epub 2022 Sep 21.
Direct N-arylation of sulfonamides is a very attractive approach for preparing pharmaceutically important N-(hetero)aryl sulfonamides because it avoids the potential genotoxic problem resulting from the previous condensation method. Most known catalytic methods suffer from limited reaction scope and inconveniency on metal catalyst and ligand availability. Here we described that the combination of copper and oxalamides (or 4-hydroxypicolinamides) offers a powerful catalytic system for N-arylation of sulfonamides. A wide range of primary and secondary sulfonamides were able to couple with a series of (hetero)aryl bromides in the presence of 2-5 mol % copper salts and oxalamides at 100 °C. Coupling of primary sulfonamides with (hetero)aryl chlorides worked well under the catalysis of Cu O and a 4-hydroxypicolinamide. The catalytic method enabled direct sulfonamidation of four chloro-containing marketed drugs and preparation of two sulfonamide drugs from the corresponding aryl halides.
直接 N-芳基化磺酰胺是一种非常有吸引力的方法，用于制备具有重要药用价值的 N-(杂)芳基磺酰胺，因为它避免了先前缩合方法所带来的潜在遗传毒性问题。大多数已知的催化方法受到反应范围有限以及金属催化剂和配体可用性的限制。在这里，我们描述了铜和草酰胺（或 4-羟基吡啶酰胺）的组合为磺酰胺的 N-芳基化提供了一个强大的催化体系。在 100°C 下，在 2-5 mol%铜盐和草酰胺存在下，一系列的（杂）芳基溴化物能够与广泛的一级和二级磺酰胺偶联。在 CuO 和 4-羟基吡啶酰胺的催化下，一级磺酰胺与（杂）芳基氯化物的偶联反应效果良好。该催化方法可直接对四种含氯的市售药物进行磺酰胺化，并可从相应的芳基卤化物制备两种磺酰胺药物。
