Iron-Catalyzed Radical Relay Enabling the Modular Synthesis of Fused Pyridines from Alkyne-Tethered Oximes and Alkenes
Iron-Catalyzed Radical Relay Enabling the Modular Synthesis of Fused Pyridines from Alkyne-Tethered Oximes and Alkenes
复制标题
铁催化自由基继电器能够从炔烃束缚的肟和烯烃模块化合成稠合吡啶
DOI：
10.1002/anie.202010752
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发表时间：
2020-10-29
影响因子：
16.6
通讯作者：
Wei, Ye
中科院分区：
文献类型：
--
作者：
Du, Fei;Li, Shi-Jun;Wei, Ye
我们合理地设计了一类新的炔系肟，并将它们应用于一个前所未有的铁催化自由基中继协议的快速组装的结构新颖和有趣的稠合吡啶的广泛阵列。该方法显示出广泛的底物范围和良好的官能团耐受性，并能够合成几种生物活性分子。此外，稠合吡啶可以通过各种简单的转化，如环化，C-H烷基化和点击反应进行双硫基官能化。密度泛函理论计算表明，反应涉及1，5-氢原子转移、5-外消旋自由基加成和环化等级联过程。此外，初步的生物学研究表明，一些稠合吡啶类化合物通过恢复脂多糖诱导模型中巨噬细胞的炎症稳态的不平衡而表现出良好的抗炎活性。
We have rationally designed a new class of alkyne-tethered oximes and applied them in an unprecedented iron-catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new and interesting fused pyridines. This method shows broad substrate scope and good functional-group tolerance and enabled the synthesis of several biologically active molecules. Furthermore, the fused pyridines could be diversely functionalized through various simple transformations, such as cyclization, C-H alkylation, and a click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5-hydrogen atom transfer, 5-exo-dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti-inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide-induced model.