Asymmetric Radical Bicyclization for Stereoselective Construction of Tricyclic Chromanones and Chromanes with Fused Cyclopropanes.
Asymmetric Radical Bicyclization for Stereoselective Construction of Tricyclic Chromanones and Chromanes with Fused Cyclopropanes.
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DOI：
10.1021/jacs.3c01618
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发表时间：
2023-05
影响因子：
15
通讯作者：
W. Lee;Jingyi Wang;Yiling Zhu;X. Zhang
中科院分区：
文献类型：
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作者：
W. Lee;Jingyi Wang;Yiling Zhu;X. Zhang
不对称自由基双环化反应是通过金属自由基催化（MRC）立体选择性地构建手性色满酮和带有稠环丙烷的色满的方法。通过优化一个通用的D2-对称手性氨基卟啉配体平台，Co（II）-金属自由基体系可以在温和的条件下均裂活化重氮丙二酸酯和含有不同烯烃官能团的α-芳基重氮甲烷，进行有效的自由基双环化，分别以高产率得到环丙烷稠合的三环色满酮和色满，同时对非对映选择性和对映选择性都有很好的控制。结合计算和实验研究，包括电子顺磁共振（EPR）检测和2，2，6，6-四甲基-1-哌啶基氧基（克里思）捕获的关键自由基中间体，揭示了工作细节的基础逐步自由基机制的钴（II）催化双环化过程。这两个催化自由基的过程提供了有效的合成工具，立体选择性建设有价值的环丙烷稠合的色满酮和色满与新产生的连续立体中心。作为合成应用的一个具体示范，Co（II）催化的自由基双环反应已被用作天然产物（+）-Radulanin J的第一个不对称全合成的关键步骤。
Asymmetric radical bicyclization processes have been developed via metalloradical catalysis (MRC) to stereoselectively construct chiral chromanones and chromanes bearing fused cyclopropanes. Through optimization of a versatile D2-symmetric chiral amidoporphyrin ligand platform, a Co(II)-metalloradical system can homolytically activate both diazomalonates and α-aryldiazomethanes containing different alkene functionalities under mild conditions for effective radical bicyclization, delivering cyclopropane-fused tricyclic chromanones and chromanes, respectively, in high yields with excellent control of both diastereoselectivities and enantioselectivities. Combined computational and experimental studies, including the electron paramagnetic resonance (EPR) detection and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) trapping of key radical intermediates, shed light on the working details of the underlying stepwise radical mechanisms of the Co(II)-catalyzed bicyclization processes. The two catalytic radical processes provide effective synthetic tools for stereoselective construction of valuable cyclopropane-fused chromanones and chromanes with newly generated contiguous stereogenic centers. As a specific demonstration of synthetic application, the Co(II)-catalyzed radical bicyclization has been employed as a key step for the first asymmetric total synthesis of the natural product (+)-Radulanin J.