Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada.
J Am Chem Soc. 2010 Aug 11;132(31):10692-705. doi: 10.1021/ja103081n.
The reactivity of C(sp(3))-H bonds adjacent to a nitrogen atom can be tuned to allow intramolecular alkane arylation under Pd(0) catalysis. Diminishing the Lewis basicity of the nitrogen lone pair is crucial for this catalytic activity. A range of N-methylamides and sulfonamides react exclusively at primary C(sp(3))-H bonds to afford the products of alkane arylation in good yields. The isolation of a Pd(II) reaction intermediate has enabled an evaluation of the reaction mechanism with a focus on the role of the bases in the C(sp(3))-H bond cleaving step. The results of these stoichiometric studies, together with kinetic isotope effect experiments, provide rare experimental support for a concerted metalation-deprotonation (CMD) transition state, which has previously been proposed in alkane C(sp(3))-H arylation. Moreover, DFT calculations have uncovered the additional role of the pivalate additive as a promoter of phosphine dissociation from the Pd(II) intermediate, enabling the CMD transition state. Finally, kinetic studies were performed, revealing the reaction rate expression and its relationship with the concentration of pivalate.
毗邻氮原子的 C(sp(3))-H 键的反应性可以通过钯（0）催化进行调节，从而允许烷烃芳基化的分子内反应。减少氮孤对的路易斯碱性对于这种催化活性至关重要。一系列 N-甲基酰胺和磺酰胺仅在伯 C(sp(3))-H 键处反应，以高产率得到烷烃芳基化产物。Pd(II)反应中间体的分离使得能够评估反应机理，重点关注碱在 C(sp(3))-H 键断裂步骤中的作用。这些化学计量研究的结果，连同动力学同位素效应实验，为以前在烷烃 C(sp(3))-H 芳基化中提出的协同金属化-去质子化（CMD）过渡态提供了罕见的实验支持。此外，DFT 计算揭示了作为促进膦从 Pd(II) 中间体解离的添加剂的特戊酸酯的附加作用，从而能够实现 CMD 过渡态。最后，进行了动力学研究，揭示了反应速率表达式及其与特戊酸酯浓度的关系。
