背景:结合使用过渡金属催化的C-H活化与芳烃环化反应已成为有机合成中的重要策略。在这项研究中,通过密度泛函理论计算研究了钯(II)催化的N-甲氧基酰胺和炔的环化反应机理。通过计算C-H活化步骤的三种不同途径,阐明了甲氧基酰胺作为导向基团的作用,表明酰胺氮作为指导基团的途径是优选的。在还原消除过渡状态下,形成不稳定的七元环,防止内酰胺形成。基于NBO分析的取代基效应研究,Hammet,并使用MoreO'Ferall-Jenks图表明,C-H活化步骤是通过亲电子协同金属化-去质子化(eCMD)机制进行的。结果表明,与给电子取代基相比,吸电子基团增加了活化势垒,并有助于早期Pd-C键形成和后期C-H键断裂。我们的计算结果与文献中提供的实验数据一致。
方法:使用高斯16软件进行所有计算。几何优化,频率分析在393.15K,和IRC计算是在理论的M06L/Def2-SVP水平进行的。校正电子能量,NBO指控,Wiberg债券指数在理论的M06L/Def2-TZVP//M06L/Def2-SVP水平上计算。在使用SMD模型的所有计算中都考虑了隐式溶剂效应,使用乙腈作为溶剂。
BACKGROUND: The combined use of transition metal-catalyzed C-H activation with aryne annulation reactions has emerged as an important strategy in organic synthesis. In this study, the mechanisms of the palladium(II)-catalyzed annulation reaction of N-methoxy amides and
arynes were computationally investigated by density functional theory. The role of methoxy amide as a directing group was elucidated through the calculation of three different pathways for the C-H activation step, showing that the pathway where amide nitrogen acts as a directing group is preferable. At the reductive elimination transition state, an unstable seven-membered ring is formed preventing the lactam formation. A substituent effect study based on an NBO analysis, Hammet, and using a More O\'Ferall-Jenks plot indicates that the C-H activation step proceeds via an electrophilic concerted metalation-deprotonation (eCMD) mechanism. The results show that electron-withdrawing groups increase the activation barrier and contribute to an early Pd-C bond formation and a late C-H bond breaking when compared with electron-donating substituents. Our computational results are in agreement with the experimental data provided in the literature.
METHODS: All calculations were performed using Gaussian 16 software. Geometry optimizations, frequency analyses at 393.15 K, and IRC calculations were conducted at the M06L/Def2-SVP level of theory. Corrected electronic energies, NBO charges, and Wiberg bond indexes were computed at the M06L/Def2-TZVP//M06L/Def2-SVP level of theory. Implicit solvent effects were considered in all calculations using the SMD model, with acetonitrile employed as the solvent.