AbstractDirectN‐arylation of sulfonamides is a very attractive approach for preparing pharmaceutically importantN‐(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 forN‐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 Cu2O 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.

中文翻译：

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磺酰胺与（杂）芳基氯/溴化物的铜催化偶联反应

摘要直接的氮‐磺胺类药物的芳基化是制备重要药用药物的一种非常有吸引力的方法氮‐（杂）芳基磺酰胺，因为它避免了先前缩合方法造成的潜在遗传毒性问题。大多数已知的催化方法都存在反应范围有限以及金属催化剂和配体可用性方面的不便。在这里，我们描述了铜和草酰胺（或 4-羟基吡啶酰胺）的组合提供了强大的催化系统氮磺酰胺类药物的芳基化。在 2-5 mol% 铜盐和草酰胺存在下，在 100 °C 下，多种伯磺酰胺和仲磺酰胺能够与一系列（杂）芳基溴偶联。Cu 催化下伯磺酰胺与（杂）芳基氯的偶联效果良好2O 和 4-羟基吡啶甲酰胺。该催化方法使得四种含氯市售药物直接磺酰胺化，并由相应的芳基卤化物制备两种磺酰胺药物。