Catalytic Chemo‐ and Regioselective Radical Carbocyanation of 2‐Azadienes for the Synthesis of α‐Amino Nitriles
Catalytic Chemo‐ and Regioselective Radical Carbocyanation of 2‐Azadienes for the Synthesis of α‐Amino Nitriles
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2-氮杂二烯的催化化学和区域选择性自由基碳氰化用于合成α-氨基腈
DOI：
10.1002/anie.202300605
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Yang, Xiaodong
中科院分区：
文献类型：
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作者：
Duan, Shengzu;Du, Ya;Wang, Lingling;Tian, Xun;Zi, Yujin;Zhang, Hongbin;Walsh, Patrick J.;Yang, Xiaodong
α-氨基腈是多种生物活性化合物和药物中的通用结构基序，并且它们在合成中充当有价值的结构单元。然而，从容易获得的支架制备α-和β-官能化的α-氨基腈仍然具有挑战性。本文报道了一种新的双催化光氧化还原/铜催化的2-氮二烯的化学和区域选择性自由基碳氰化反应，通过氧化还原活性酯（RAE）和三甲基硅腈获得官能化的α-氨基腈。该级联方法采用广泛的RAE并以50- 95%的产率提供相应的α-氨基腈结构单元（51个实例，区域选择性>95：5）。产物转化为珍贵的α-氨基腈和α-氨基酸。机理研究表明，自由基级联耦合过程。
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.