Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
College of Chemistry and Chemical engineering, Yan'an University , Yan'an 716000, P. R. China.
J Am Chem Soc. 2017 Mar 15;139(10):3904-3910. doi: 10.1021/jacs.7b00823. Epub 2017 Mar 3.
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/C-C 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.
密度泛函理论研究表明，使用 4-氰基吡啶和双（频哪醇）二硼原位生成的吡啶-硼自由基可用作双功能“试剂”，它不仅是吡啶的前体，而且还是硼自由基。由于这种自由基的独特反应性，可以通过新型自由基加成/C-C 偶联反应，以α,β-不饱和酮和 4-氰基吡啶为原料合成 4-取代吡啶衍生物。进行了几项对照实验，为所提出的机制提供了支持性证据。除了烯酮之外，该反应范围还可以扩展到各种硼自由基受体，包括各种醛和酮、芳基亚胺和炔酮。最后，该转化被应用于复杂药物分子的后期修饰。
