Franzoni Ivan, Yoon Hyung, García-López José-Antonio, Poblador-Bahamonde Amalia Isabel, Lautens Mark
Davenport Research Laboratories , Department of Chemistry , University of Toronto , 80 St. George St. , Toronto , Ontario M5S 3H6 , Canada . Email:
Departamento de Química Inorgánica , Universidad de Murcia , Campus de Espinardo , 30100 Murcia , Spain . Email:
Chem Sci. 2017 Dec 8;9(6):1496-1509. doi: 10.1039/c7sc04709f. eCollection 2018 Feb 14.
The mechanism of the palladium-catalyzed spirocyclization of acrylamides has been investigated by density functional theory and experimental studies. The results support a mechanistic pathway that proceeds oxidative addition, intramolecular carbopalladation, C-H bond activation, and migratory insertion sequence. The M06L/def2-TZVPP//BP86/6-31G(d,p)/LANL2DZ level of theory used and the inclusion of solvent effects provide results in good agreement with the experimental data. The C-H bond activation step proceeds a concerted -sphere metallation deprotonation mechanism that explains the absence of a measurable kinetic isotopic effect. The subsequent intermolecular migratory insertion of arynes is significantly faster than the insertion of internal alkynes. Furthermore, the regioselectivities calculated in the case of unsymmetrical reactants are remarkably close to the experimental values. Evaluation of the potential energy surfaces for specific substrates provides an explanation for the lack of product formation observed experimentally. Finally, the computational and experimental analyses of potential side reactions are also presented and support the initially proposed mechanism.
通过密度泛函理论和实验研究，对钯催化丙烯酰胺的螺环化反应机理进行了研究。结果支持了一种通过氧化加成、分子内碳钯化、C-H键活化和迁移插入序列进行的反应机理。所使用的M06L/def2-TZVPP//BP86/6-31G(d,p)/LANL2DZ理论水平以及溶剂效应的纳入，提供了与实验数据高度吻合的结果。C-H键活化步骤通过协同的球外金属化去质子化机理进行，这解释了没有可测量的动力学同位素效应的原因。随后，芳炔的分子间迁移插入明显快于内炔的插入。此外，在不对称反应物情况下计算的区域选择性与实验值非常接近。对特定底物势能面的评估为实验中观察到的产物形成缺失提供了解释。最后，还介绍了潜在副反应的计算和实验分析，支持了最初提出的机理。
