Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Pharmacy, Yunnan University, Kunming, 650500, P. R. China.
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA, USA.
Angew Chem Int Ed Engl. 2023 May 2;62(19):e202300605. doi: 10.1002/anie.202300605. Epub 2023 Mar 31.
α-Amino nitriles are versatile structural motifs in a variety of biologically active compounds and pharmaceuticals and they serve as valuable building blocks in synthesis. The preparation of α- and β-functionalized α-amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/copper-catalyzed chemo- and regioselective radical carbocyanation of 2-azadienes to access functionalized α-amino nitriles by using redox-active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding α-amino nitrile building blocks in 50-95 % yields (51 examples, regioselectivity >95 : 5). The products were transformed into prized α-amino nitriles and α-amino acids. Mechanistic studies suggest a radical cascade coupling process.
α-氨基腈是各种生物活性化合物和药物中多功能的结构基序，它们可用作合成中的有价值的构建块。然而，从易得的支架制备α-和β-官能化的α-氨基腈仍然具有挑战性。在此，我们报道了一种新型的双催化光氧化还原/铜催化的化学和区域选择性自由基碳氰化反应，可通过使用氧化还原活性酯（RAE）和三甲基硅氰化物，从 2-氮杂二烯制备功能化的α-氨基腈。该级联过程采用了广泛的 RAE，并以 50-95%的收率（51 个实例，区域选择性>95:5）提供了相应的α-氨基腈构建块。产物可转化为有价值的α-氨基腈和α-氨基酸。机理研究表明这是一个自由基级联偶联过程。
