N-Alkylation of Amines Catalyzed by a Ruthenium-Pincer Complex in the Presence of in situ Generated Sodium Alkoxide

We report the use of ruthenium-NNN-pincer complexes of the type ((NNN)-N-R2)RuCl2(PPh3) (R = tBu, iPr, Cy and Ph) for the catalytic N-alkylation of primary amines under solvent-free conditions. For the first time, the base that is required to promote these reactions is generated in situ from the alcohol by the use of sodium. The resulting sodium alkoxide regenerates the alcohol substrate while acting as the water scavenger thus mitigating the need of an additional base. Among the catalysts screened, ((NNN)-N-tBu2)RuCl2(PPh3) (0.02 mol-%) gives very high turnovers and good yields at 140 degrees C. The ((NNN)-N-tBu2)RuCl2(PPh3) catalyzed N-alkylation tolerates a variety of amine and alcohol substrates. While excellent turnover (29000) was obtained for the ((NNN)-N-tBu2)RuCl2(PPh3) (0.002 mol-%) catalyzed alkylation of aniline with cyclohexyl methanol, the turnovers obtained in the corresponding catalytic methylation of p-anisidine was also very high (12000). The ((NNN)-N-tBu2)RuCl2(PPh3) catalyzed reactions have also been accomplished under open-vessel conditions resulting in a net dehydrogenative coupling reaction. This protocol has been used to transform benzene-1,2-diamines to benzimidazoles with high productivity (12000 turnovers). DFT studies indicate that while beta-hydride elimination is rate-determining (RDTS: 24.31 kcal/mol) for the alcohol dehydrogenation segment which is endothermic, insertion of the imine is rate-determining (RDTS: 11.26 kcal/mol) for its hydrogenation that is exothermic.