Interrogating Explicit Solvent Effects on the Mechanism and Site‐Selectivity of Aryl Halide Oxidative Addition to L ₂ Pd(0)

We report a study of solvent effects on the rate, selectivity, and mechanism of (hetero)aryl (pseudo)halide oxidative addition to Pd(PCy₃)₂ as an exemplar of L₂Pd(0) species. First, 2-chloro-3-aminopyridine is observed to undergo faster oxidative addition in toluene compared to more polar solvents, which is not consistent with the trend we observe with many other 2-halopyridines. We attribute this to solvent basicity hydrogen bonding between solvent and substrate. Greater hydrogen bond donation from the substrate leads to a more electron-rich aromatic system, and therefore slower oxidative addition. We demonstrate how this affects rate and site-selectivity for hydrogen bond donating substrates. Second, electron-deficient multihalogenated pyridines exhibit improved site-selectivity in polar solvents, which we attribute to different C-X sites undergoing oxidative addition by two different mechanisms. The C-X site that favours the more polar nucleophilic displacement transition state is preferred over the site that favours a less-polar 3-centered transition state. Finally, (hetero)aryl triflates consistently undergo faster oxidative addition in more polar solvents, which we attribute to highly polar nucleophilic displacement transition states. This leads to improved site-selectivity for C-OTf oxidative addition, even in the presence of highly reactive 2-pyridyl halides.