Metal-Free Reductive Coupling of para-Quinone Methides with 4-Cyanopyridines Enabled by Pyridine-Boryl Radicals: Access to Pyridylated Diarylmethanes with Anti-Cancer Activity
Metal-Free Reductive Coupling of para-Quinone Methides with 4-Cyanopyridines Enabled by Pyridine-Boryl Radicals: Access to Pyridylated Diarylmethanes with Anti-Cancer Activity
复制标题
吡啶硼基自由基实现对醌甲基化物与 4-氰基吡啶的无金属还原偶联：获得具有抗癌活性的吡啶化二芳基甲烷
DOI：
10.1002/chem.202200264
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Gui-Ting Song
中科院分区：
文献类型：
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作者：
Chuan-Hua Qu;Li-Xia Gao;Yan Tang;Yuan Liu;Xiao-Qin Luo;Gui-Ting Song
本文报道了使用双（频哪醇合）二硼（B2 pin 2）作为模板试剂通过吡啶-硼基自由基诱导的对苯醌甲基化物（p-QM）和4-氰基吡啶之间的还原偶联来生产吡啶基化二芳基甲烷的简化方案。无金属工艺的特点是操作简单，化学选择性（1，2-vs. 1，6-选择性）优异，底物范围广，官能团相容性好。机理研究为二芳基甲基自由基和吡啶硼基自由基之间的还原交叉偶联过程提供了重要的见解。此外，部分吡啶基化二芳基甲烷产物针对一组癌细胞系进行了筛选，并且证实3 v显著抑制头颈部鳞状细胞癌（HNSCC）细胞的增殖。该方法为制备具有抗肿瘤活性的新型先导化合物提供了一个平台。
Reported herein is a streamlined protocol to produce pyridylated diarylmethanes through pyridine‐boryl radical induced reductive coupling betweenpara‐quinone methides (p‐QMs) and 4‐cyanopyridines using bis(pinacolato)diboron (B2pin2) as a templated reagent. The metal‐free process is characterized by an operationally simple approach, excellent chemoselectivity (1,2‐ vs. 1,6‐selectivity), and a broad substrate scope with good functional group compatibility. The mechanistic studies provided important insights into the reductive cross‐coupling process between diarylmethyl radical and pyridine‐boryl radical. Moreover, part of the obtained pyridylated diarylmethane products were screened against a panel of cancer cell lines, and3 vwas confirmed to significantly inhibit the proliferation of head and neck squamous cell carcinoma (HNSCC) cells. This method offers a platform for the preparation of new lead compounds with antitumor activity.