Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
J Am Chem Soc. 2017 Dec 13;139(49):17935-17944. doi: 10.1021/jacs.7b08902. Epub 2017 Nov 30.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a highly effective reagent for promoting C-H bond functionalization. The oxidative cleavage of benzylic and allylic C-H bonds using DDQ can be coupled with an intra- or intermolecular nucleophilic addition to generate new carbon-carbon or carbon-heteroatom bonds in a wide range of substrates. The factors that control the reactivity of these reactions are well-defined experimentally, but the mechanistic details and the role of substituents in promoting the transformations have not been firmly established. Herein, we report a detailed computational study on the mechanism and substituent effects for DDQ-mediated oxidative C-H cleavage reactions in a variety of substrates. DFT calculations show that these reactions proceed through a hydride transfer within a charge transfer complex. Reactivity is dictated by the stability of the carbocation intermediate, the degree of charge transfer in the transition states, and, in certain cases, secondary orbital interactions between the π orbital of the forming cation and the LUMO of DDQ. A linear free energy relationship was established to offer a predictive model for reactivity of different types of C-H bonds based on the electronic properties of the substrate.
2,3-二氯-5,6-二氰基-1,4-苯醌（DDQ）是一种非常有效的试剂，可促进 C-H 键功能化。使用 DDQ 氧化裂解苄基和烯丙基 C-H 键可以与分子内或分子间亲核加成反应偶联，在广泛的底物中生成新的碳-碳或碳-杂原子键。控制这些反应活性的因素在实验上已得到很好的定义，但反应机制的细节和取代基在促进转化中的作用尚未得到牢固确立。在此，我们报告了对各种底物中 DDQ 介导的氧化 C-H 裂解反应的机制和取代基效应的详细计算研究。DFT 计算表明，这些反应通过电荷转移配合物中的氢原子转移进行。反应性由碳正离子中间体的稳定性、过渡态中的电荷转移程度以及在某些情况下形成阳离子的π轨道与 DDQ 的 LUMO 之间的次级轨道相互作用决定。建立了线性自由能关系，为基于底物电子性质的不同类型 C-H 键的反应性提供了预测模型。
