Palladium-Catalyzed Coupling Reaction Of P-Xylene

Biaryls preparation is one of the most important processes in modern organic synthesis, since various biaryls are fundamental structures in natural products, pharmaceuticals and organic conductors. At present, Suzuki reaction or Stille reaction is still a main way to form biaryls, which involves a coupling of an aryl halide with an organometallic fragment. However, those multiple-step reactions including the halogenation of arenes and the stoichiometric metalation of arenes are necessary before the couplings of them occur.Diarylmethane derivatives are also useful intermediates in organic and polymer synthesis. Normally, they can be synthesized by the benzylation of arenes with benzyl chlorides or benzyl alcohols in the presence of various inorganic acid, organic solid acid or other catalysts, but both the substituted benzyl chlorides and benzyl alcohols are not easily available.In contrast, if C-H bonds in alkyl-substituted benzenes can be activated by transition-metal catalysts to directly yield biaryls or diarylmethane derivatives under mild conditions, it can effectively reduce steps of synthesis and consumptions of halogens as well as many other reagents. Thus, the coupling reaction of simple arenes via C-H activation should be an environmentally benign, economical and convenient method in organic synthesis.Selective C-H bond activation or functionalization is a challenging subject for researchers in organic and organometallic chemistry. More recently, a few studies disclosed the activation of aryl versus benzylic C-H bonds of alkyl-substituted benzenes. In these selective C-H bond activation processes, steric and electronic factors from both transition metal complexes and arenes were emphasized and investigated. Herein, we have mainly introduced the aryl and benzylic C-H bonds in p-xylene could be selectively activated to form biaryl- or diarylmethane as a major product in a catalytic system of Pd(OAc)2/CF3CO2H(TFA)/K2S2O8. It is notable that the regioselectivity of this homocoupling could be readily controlled by tuning the concentration of TFA in this system.The effects of various catalysts, oxidants, acids and temperature etc on this homocoupling were investigated. With higher TFA concentration, diarylmethane was produced much more in the coupling of p-xylene, otherwise biaryl was the major product. To be compared with p-xylene, moreover, other alkylarenes with different steric hindrance were also employed in these catalytic coupling reactions. The results may suggest that the steric hindrance of arenes could block the formation of biaryls through double aryl C-H activations.A tentative mechanism of Pd(II)-catalyzed coupling of p-xylene via regioselective C-H activation in TFA was proposed. Furthermore, it was partly supported by the cross-couplings of mesitylene with benzene and naphthalene, respectively, in a higher concentration of TFA, and a few tests involving deuterated arenes.