Mechanistic Study of Palladium-Catalyzed Oxidative C–H/C–H Coupling of Polyfluoroarenes with Simple Arenes

Abstract

Pd-catalyzed oxidative C–H/C–H coupling reaction is an emerging type of C–H activation reaction, which attracts great interests because both reaction partners do not require pre-functionalization. In the present study, we employed DFT methods to investigate the mechanism of Pd(OAc)2-catalyzed oxidative C–H/C–H coupling of pentafluorobenzene with benzene. Four possible pathways were examined in the C–H activation part: path A benzene-pentafluorobenzene mechanism (C–H activation of benzene occurs before the C–H activation of pentafluorobenzene), path B pentafluorobenzene-benzene mechanism (C–H activation of benzene occurs after the C–H activation of pentafluorobenzene), path C benzene-pentafluorophenylsilver mechanism (C–H activation of benzene and subsequent transmetalation with pentafluorophenyl silver complex), path D pentafluorophenylsilverbenzene mechanism (transmetalation with pentafluorophenyl silver complex and subsequent C–H activation of benzene). Based on the calculations, the sequences of two C–H activation steps are found to be different in the oxidative couplings of same substrates (i.e. pentafluorobenzene and benzene) in different catalytic systems, where the additive Ag salts played a determinant role. In the absence of Ag salts, the energetically favored pathway is path B (i.e. the C–H activation of pentafluorobenzene takes place before the C–H cleavage of benzene). In contrast, with the aid of Ag salts, the coordination of pentafluorophenylsilver to Pd center could occur easily with a subsequent C–H activation of benzene in the second step, and the second step significantly raises the whole reaction barrier. Alternatively, in the presence of Ag salts, the kinetically preferred mechanism is path C (i.e. the C–H activation of benzene takes place in the first step followed by transmetalation with pentafluorophenylsilver complex), which is similar to path A. The calculations are consistent with the H/D exchange experiment and kinetic isotope effects. Thus the present study not only offers a deeper understanding of oxidative C–H/C–H coupling reaction, but also provides helpful insights to further development of more efficient and selective oxidative C–H/C–H coupling reactions.