This study investigates the mechanism of metal-free pyridine phosphination with P(OEt)3, PPh3, and PAr2CF3 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)3 occurs in five stages, and ethyl abstraction is the rate-determining step. Meanwhile, 2-Ph-pyridine phosphination with PPh3 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 PAr2CF3 is similar to that with PPh3, 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.
Keywords: C–H fluoroalkylation; DFT; mechanism; metal free; phosphination.