Cu(OTf) 2 -Mediated Cross-Coupling of Nitriles and N-Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products**
Cu(OTf) 2 -Mediated Cross-Coupling of Nitriles and N-Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products**
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Cu(OTf) 2 -介导腈和 N-杂环与芳基硼酸的交叉偶联生成硝基和吡啶基产品**
DOI：
10.1002/ange.202016811
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发表时间：
2021
影响因子：
--
通讯作者：
Bell N
中科院分区：
文献类型：
--
作者：
Bell N
金属催化的C-N交叉偶联通常通过还原消除含共价C-和N-配体的金属络合物而形成C-−-N键。我们已经确定了一种铜介导的C-N交叉偶联，它在成键过程中使用了与键的N-配体，与传统方法相比，它产生了反应性阳离子产物。机理研究表明，这一过程是通过将芳基有机硼转化为含有中性N-配体的CuII络合物来进行的，如腈或N-杂环。随后生成一个假定的CuIII络合物，使氧化C-N偶联能够发生，提供了氮化钛中间体和吡啶产品。该反应对一系列N(Sp2)和N(Sp2)前体是通用的，可用于药物合成和后期N-芳基化，并从力学上证明了方法学的局限性。
Metal‐catalyzed C–N cross‐coupling generally forms C−N bonds by reductive elimination from metal complexes bearing covalent C‐ and N‐ligands. We have identified a Cu‐mediated C–N cross‐coupling that uses a dative N‐ligand in the bond‐forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a CuIIcomplex bearing neutral N‐ligands, such as nitriles or N‐heterocycles. Subsequent generation of a putative CuIIIcomplex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp2) precursors and can be applied to drug synthesis and late‐stage N‐arylation, and the limitations in the methodology are mechanistically evidenced.