Pincer–Ruthenium-Catalyzed β-Methylation of Alcohols

The synthesis and characterization of three NNN pincer–Ru complexes based on bis(imino)pyridine ligands have been reported. These complexes along with other previously reported pincer–Ru catalysts based on bis(imino)pyridine and 2,6-bis(benzimidazol-2-yl)pyridine ligands have been employed to accomplish the β-methylation of 2-phenylethanol and the selective β-dimethylation of 1-phenylethanol using methanol as an alkylating agent. In general, the pincer–ruthenium complex [(^MeBim₂NNN)RuCl(PPh₃)₂]Cl based on the dimethyl-substituted 2,6-bis(benzimidazol-2-yl)pyridine ligand was found to be the most efficient among the considered catalysts. Under the best conditions, in the [(^MeBim₂NNN)RuCl(PPh₃)₂]Cl (0.5 mol %)-catalyzed reactions in the presence of 0.75 equiv of KOH using 7.5 equiv of methanol, up to 92% yield of β-methylated 2-phenylethanol was obtained at 140 °C. On the other hand, selective β-dimethylation of 1-phenylethanol could be achieved in the [(^MeBim₂NNN)RuCl(PPh₃)₂]Cl (0.5 mol %)-catalyzed reactions in the presence of 2 equiv of Na using 24.8 equiv of methanol. The developed synthetic protocol is generic in nature and could be applied to accomplish β-methylation and selective β-dimethylation of about 35 substrates. The reaction has also been probed from a mechanistic point of view. While mercury poisoning experiments revealed the reaction to be catalyzed by well-defined molecular catalysts, kinetic experiments indicated that the rate of product formation has a linear dependence on the concentrations of both the pincer–ruthenium catalyst and 2-phenylethanol. DFT studies complement the observed secondary kinetic isotope effect (KIE) of 1.56 and suggest that dehydrogenolysis involving σ-bond metathesis of methanol with the Ru–H species leading to the evolution of hydrogen is the rate-determining step with a barrier of 24.06 kcal/mol. The Ru–H and Ru–OMe species, being the lowest-energy intermediates of the catalytic cycle, are likely to be the resting state of the cycle and have been detected by NMR and HRMS analysis.