School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China.
Sci Rep. 2017 Mar 8;7:43579. doi: 10.1038/srep43579.
Transition metal-catalyzed radical-radical cross-coupling reactions provide innovative methods for C-C and C-heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C-N radical-radical cross-coupling reaction. The concerted coupling pathway, in which a C-N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)-N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)-N species before C-N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)-N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)-N intermediate. The higher activation free energy for N-N radical-radical homo-coupling is attributed to the mismatch of Cu(II)-N species with the nitrogen radical because the electrophilicity for both is strong.
过渡金属催化的自由基-自由基交叉偶联反应为 C-C 和 C-杂原子键的构建提供了创新的方法。本研究进行了理论研究，以揭示铜催化的 C-N 自由基-自由基交叉偶联反应的机理和选择性。协同偶联途径，即通过碳自由基对 Cu(II)-N 物种的氮原子的直接亲核加成形成 C-N 键，被证明在动力学上是不利的。分步偶联途径，即在 C-N 键形成之前，碳自由基与 Cu(II)-N 物种结合，被证明是可能的。Cu(II)-N 中间体上的 Mulliken 原子自旋密度分布和前沿分子轨道分析表明，Cu 位比 N 位更具反应性；因此，碳自由基优先与金属中心反应。交叉偶联的化学选择性也可以通过碳自由基、氮自由基和 Cu(II)-N 中间体的电子兼容性的差异来解释。N-N 自由基同偶联的更高的活化自由能归因于 Cu(II)-N 物种与氮自由基不匹配，因为两者的亲电性都很强。
