Sulfur functional groups are common motifs in bioactive molecules. Sulfonamides are most prevalent but related aza-derivatives, in which oxygen atoms are replaced by imidic nitrogens, such as sulfoximines and sulfonimidamides, are gaining attraction. Despite this activity, the double aza-variants of sulfonamides, termed sulfondiimidamides, are almost completely absent from the literature. The reason for this is poor synthetic accessibility. Although a recent synthesis has established sulfondiimidamides as viable motifs, the length of the route and the capricious nature of the key sulfondiimidoyl fluoride intermediates mean that direct application to discovery chemistry is challenging. Herein, we describe a two-step synthesis of sulfondiimidamides, exploiting a hypervalent iodine-mediated amination as the key step. The starting materials are organometallic reagents, an unsymmetrical sulfurdiimide, and amines. The method allowed >40 examples to be prepared, including derivatives of three sulfonamide-based drugs. The operational simplicity, broad scope, and concise nature make this route attractive for discovery chemistry applications.

中文翻译：

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磺二酰亚胺的模块化两步法

硫官能团是生物活性分子中的常见基序。磺胺类是最普遍但相关的氮杂衍生物，其中氧原子被亚氨基氮取代，例如亚砜​​亚胺和磺胺类，越来越受到关注。尽管有这种活性，但文献中几乎完全没有磺胺的双氮杂变体，称为磺二亚胺。其原因是合成可访问性差。尽管最近的合成已确定磺二亚胺作为可行的基序，但路线的长度和关键磺二亚胺中间体的反复无常意味着直接应用于发现化学具有挑战性。在这里，我们描述了磺二亚胺的两步合成，利用高价碘介导的胺化作为关键步骤。起始材料是有机金属试剂、不对称硫二亚胺和胺。该方法允许制备超过 40 个实例，包括三种磺胺类药物的衍生物。操作简单、范围广和简洁的性质使这条路线对发现化学应用具有吸引力。