The Mechanism of Acceptorless Amine Double Dehydrogenation by N,N,N-Amide Ruthenium(II) Hydrides: A Combined Experimental and Computational Study

A detailed mechanistic analysis of the acceptorless double dehydrogenation of primary amines to form nitriles by HRu(bMepi)(PPh3)(2) (1, bMepi = 1,3-bis(6'-methyl-2'-pyridylimino)isoindolate) is presented. The presence of the ortho-CH3 substituents on bMepi is critical for amine dehydrogenation, and no catalysis was observed with HRu(bpi)(PPh3)(2) (1-bpi, bpi = 1,3-bis(2'-pyridylimino)isoindolate). Outer-sphere, inner-sphere, and hemilabile pathways were evaluated through ligand substitution and kinetic studies, catalyst modifications, and computational analysis. We propose an inner-sphere mechanism in which a Ru-hydride is protonated by coordinated amine followed by H-2 release, which forms a Ru-amido intermediate. The stability of Ru-amido species was evaluated through NBO, MM, and NCI analyses, revealing steric pressure as well as weak noncovalent interactions between the coordinated amido nitrogen atom and the ortho-alkyl substituents, and these interactions impact the overall thermodynamic profile for amine dehydrogenation by 1. Finally, the preference for double dehydrogenation over the transamination reaction is attributed to a high binding constant of the imine intermediate and fast kinetics of a second dehydrogenation.