Observing the Agostic Hydrogen in Pd(II)-Catalyzed Aromatic C-H Activation

Direct C-H activation and functionalization offer a convenient protocol for pharmaceutical and material syntheses. Although versatile mechanisms have been proposed to depict transition-metal-catalyzed C-H activation, to date, the shared key agostic hydrogen intermediate in several major mechanisms has not been observed yet, which apparently puzzles the mechanism-based catalyst design. This work reports the direct observations of this intermediate in Pd(II)/Sc(III)-catalyzed C-H activation of acetanilides, and its stability and reactivity in C-H activation are investigated. Remarkably, this intermediate is only observed in electron-rich acetanilides, and the metasubstituent with increased sigma(m) constant generally accelerates C-H activation, a characteristic of the base-assisted C-H activation mechanism. This study has unveiled the masks of this intermediate with an understanding of its first-hand physicochemical properties, shedding new light on mechanism-based catalyst design.

Automated summary

Direct C-H activation and functionalization provide a convenient method for pharmaceutical and material synthesis. This study reports the direct observation of the key agostic hydrogen intermediate in Pd(II)/Sc(III)-catalyzed C-H activation and investigates its properties and reactivity. The intermediate is only observed in electron-rich acetanilides and exhibits characteristic features of a specific activation mechanism.