Explicit roles of diverse directing groups in determining transition state energy and reaction exothermicity of C–H activation pathways

Abstract

The aim of this paper was to explore, from a computational perspective, the explicit effects of diverse directing groups on the main kinetic and thermodynamic parameters for Pd(OAc)₂-catalyzed aromatic C–H activation. As a prototype of undirected C–H activation reactions, palladation of benzene with Pd(OAc)₂ has been investigated by using DFT calculations, which has revealed that the final palladated benzene is evidently unstable by ca. 7.1 kcal mol⁻¹ in free-energy with respect to the initial materials, though the proton-transfer barrier is estimated to be merely 21.5 kcal mol⁻¹. Then we performed a series of DFT characterization studies on the directed C–H activation pathway using 16 selected directing group systems. Comparing with the data of benzene and Pd(OAc)₂, 7 of the 16 studied systems (Type A) were found to stabilize the final palladacycle yet increase the proton-transfer activation barrier, and the remaining 9 (Type B) could strongly stabilize the final palladacycle but have a minor effect on the proton-transfer activation free-energy barrier, indicating that the mediation of the directing group might not necessarily lower the free-energy barrier of C–H activation. Lastly, the main structure factors, in determining these variations of key energetic parameters, have been discussed in great detail.