ETH Zürich, Vladimir-Prelog-Weg 3, HCI, 8093 Zürich, Switzerland.
J Am Chem Soc. 2020 Dec 23;142(51):21548-21555. doi: 10.1021/jacs.0c11025. Epub 2020 Dec 10.
Unprotected, primary 2-azidoamines are versatile precursors to vicinal diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through an iron-catalyzed difunctionalization of alkenes. A wide array of alkene substrates are tolerated, including complex drug-like molecules and a tripeptide. Facile derivatizations of the azidoamine group demonstrate the versatility of this masked diamine motif in chemoselective, orthogonal transformations. Applications of the methodology in the concise synthesis of RO 20-1724 as well as in the formal total syntheses of both (±)-hamacanthin B and (±)-quinagolide further demonstrate the broad synthetic potential of this highly functional-group-tolerant reaction.
未保护的伯 2-叠氮胺是顺式二胺的多功能前体，顺式二胺是生物活性化合物中最常见的结构单元之一。在此，我们报告了通过铁催化的烯烃双官能化反应来实现其操作简单的合成方法。该反应对各种烯烃底物都具有耐受性，包括复杂的类药物分子和三肽。叠氮胺基团的易衍生化展示了这种掩蔽的二胺结构单元在化学选择性、正交转化中的多功能性。该方法在 RO 20-1724 的简洁合成以及 (±)-hamacanthin B 和 (±)-quinagolide 的正式全合成中的应用进一步证明了这种高度官能团容忍反应的广泛合成潜力。
