Direct Asymmetric Aza-Vinylogous-Type Michael Additions of Nitrones from Isatins to Nitroalkenes
Direct Asymmetric Aza-Vinylogous-Type Michael Additions of Nitrones from Isatins to Nitroalkenes
复制标题
从靛红到硝基烯烃的硝酮直接不对称氮杂乙烯型迈克尔加成
DOI：
10.1002/chem.201701290
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发表时间：
2017
影响因子：
4.3
通讯作者：
Chen Ying-Chun
中科院分区：
文献类型：
--
作者：
Zhan Gu;Shi Ming-Lin;Lin Wei-Jia;Ouyang Qin;Du Wei;Chen Ying-Chun
硝酮通常作为1，3-偶极和亲电子试剂，分别提供有价值的异恶唑烷和N-羟基产物。它们也可以转化为硝酮叶立德物种，并进行[3+2]环加成反应以获得N-羟基吡咯烷。在这里，提出了由靛红到硝基烯烃的硝酮的不对称直接氮杂-乙烯基-型加成，由双官能硫脲-叔胺催化，以优异的立体选择性提供具有扩展的碳骨架的高度官能化的硝酮。值得注意的是，硝酮部分可以很容易地去除，从而提供烷基胺型物质的形式不对称α官能化。此外，剩余的亲电硝酮基序使随后的环化，以构建高分子复杂性和多样性的螺环产物，这可能有潜在的药物发现的应用。
Nitrones commonly act as 1,3‐dipoles and electrophiles to furnish valuable isoxazolidine andN‐hydroxyl products, respectively. They also can be converted to nitrone ylide species and undergo [3+2] formal cycloadditions to accessN‐hydroxyl pyrrolidines. Here, asymmetric direct aza‐vinylogous‐type additions of nitrones from isatins to nitroalkenes are presented, catalyzed by a bifunctional thiourea‐tertiary amine, affording highly functionalized nitrones with extended carbon skeletons in excellent stereoselectivity. Notably, the nitrone moiety can be easily removed, thus furnishing the formal asymmetric α‐functionalization of alkylamine‐type substances. Moreover, the remaining electrophilic nitrone motif enables the subsequent annulations to construct spirocyclic products in high molecular complexity and diversity, which might have potential applications for drug discovery.