Factors Controlling the Reactivity of Heteroarenes in Direct Arylation with Arylpalladium Acetate Complexes

The
palladium-catalyzed direct arylation of heteroarenes with aryl
halides has emerged as a viable alternative to conventional cross-coupling
reactions. This paper reports a detailed mechanistic study on factors
controlling the reactivity of heteroarenes in direct arylation with
well-defined models of the presumed intermediate [PdAr­(O2CMe-κ2O)­L] (1). Although
recent theoretical studies have provided a reasonable description
of the mechanism of C–H bond cleavage by 1, its
model compounds so far tested have been evidently less reactive than
that expected. We found that [PdPh­(O2CMe-κ2O)­(PPh3)] (1a) and [Pd­(2,6-Me2C6H3)­(O2CMe-κ2O)­(PPh3)] (1c), generated
in situ from isolated [PdPh­(μ-O2CMe)­(PPh3)]2 (4a) and [Pd­(2,6-Me2C6H3)­(μ-O2CMe)­(PPh3)]4 (4c), respectively, react with a variety of
heteroarenes in almost quantitative yields. The reactivity order of
heteroarenes was evaluated by competitive reactions, showing that
benzothiazole (8) is significantly less reactive than
2-methylthiophene (6), despite the acidity of 8 (pKa = 27) being much higher than that
of 6 (pKa = 42). This reason
was examined by kinetic experiments using 1c as well
as DFT calculations using the model compound [PdPh­(O2CMe-κ2O)­(PH3)] (1d). Both
heteroarenes reacted with 1 via a sequence of three elementary
processes (i.e., substrate coordination, C–H bond cleavage,
and C–C reductive elimination), but their energy profiles were
significantly different from each other. The reaction of 6 obeyed simple second-order kinetics, and the deuterium-labeling
experiments and DFT calculations indicated the occurrence of rate-determining
reductive elimination. On the other hand, the reaction of 8 displayed saturation kinetics due to the occurrence of relatively
stable coordination of 8 prior to C–H bond cleavage.
This coordination stability enhances the activation barrier for C–H
bond cleavage, thereby causing the modest reactivity of 8. Thus, although the previous mechanistic studies on direct arylation
have been focused largely on the C–H bond cleavage process,
not only the C–H bond cleavage but also the substrate coordination
and C–C reductive elimination must be considered.