Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study
Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study
复制标题
使用吡啶-硼基自由基通过自由基加成/偶联机制无金属合成 C-4 取代的吡啶衍生物：计算和实验相结合的研究。
DOI：
10.1021/jacs.7b00823
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Shuhua Li
中科院分区：
文献类型：
--
作者：
Guoqiang Wang;Jia Cao;Liuzhou Gao;Wenxin Chen;Wenhao Huang;Xu Cheng;Shuhua Li
密度泛函理论研究表明，用4-氰吡啶和双（pinacolato）二硼原位生成的吡啶-硼基自由基可作为双功能“试剂”，既可作为吡啶前体，又可作为硼基自由基。由于这些自由基具有独特的反应活性，可以利用α、β-不饱和酮和4-氰吡啶通过一种新的自由基加成/CC偶联机制合成4-取代吡啶衍生物。进行了几个对照实验，为提出的机制提供支持性证据。除烯酮外，还可扩展到广泛的硼基自由基受体，包括各种醛类和酮类、芳基亚胺类和炔酮类。最后，将这种转化应用于复杂药物分子的后期修饰。
Density functional theory investigations revealed that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional “reagent”, which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/CC coupling mechanism. Several controlled experiments were conducted to provide supportive evidence for the proposed mechanism. In addition to enones, the scope could be extended to a wide range of boryl radical acceptors, including various aldehydes and ketones, aryl imines and alkynones. Lastly, this transformation was applied in the late-stage modification of a complicated pharmaceutical molecule.