School of Life Science and Chemistry, Jiangsu Second Normal University, Nanjing 210013, China.
School of Environmental Science, Nanjing Xiaozhuang University, Nanjing 211171, China.
Molecules. 2022 Sep 3;27(17):5694. doi: 10.3390/molecules27175694.
This study investigates the mechanism of metal-free pyridine phosphination with P(OEt), PPh, and PArCF using density functional theory calculations. The results show that the reaction mechanism and rate-determining step vary depending on the phosphine and additive used. For example, phosphination of pyridine with P(OEt) occurs in five stages, and ethyl abstraction is the rate-determining step. Meanwhile, 2-Ph-pyridine phosphination with PPh is a four-step reaction with proton abstraction as the rate-limiting step. Energy decomposition analysis of the transition states reveals that steric hindrance in the phosphine molecule plays a key role in the site-selective formation of the phosphonium salt. The mechanism of 2-Ph-pyridine phosphination with PArCF is similar to that with PPh, and analyses of the effects of substituents show that electron-withdrawing groups decreased the nucleophilicity of the phosphine, whereas aryl electron-donating groups increased it. Finally, TfO plays an important role in the C-H fluoroalkylation of pyridine, as it brings weak interactions.
本研究使用密度泛函理论计算考察了无金属吡啶膦化反应中 P(OEt)、PPh 和 PArCF 的反应机理。结果表明，反应机理和速率决定步骤取决于所用的膦和添加剂。例如，吡啶与 P(OEt)的膦化反应分五个阶段进行，乙基抽提是速率决定步骤。同时，PPh 与 2-Ph-吡啶的膦化反应是四步反应，质子抽提是限速步骤。过渡态的能量分解分析表明，膦分子中的空间位阻在磷翁盐的选择性形成中起着关键作用。2-Ph-吡啶与 PArCF 的膦化反应机理与 PPh 相似，取代基效应分析表明，吸电子基团降低了膦的亲核性，而芳基供电子基团则增加了其亲核性。最后，TfO 在吡啶的 C-H 氟烷基化中起着重要作用，因为它带来了弱相互作用。
