Mechanism of N,N,N‑Amide Ruthenium(II) Hydride Mediated Acceptorless Alcohol Dehydrogenation: Inner-Sphere β‑H Elimination versus Outer-Sphere Bifunctional Metal–Ligand Cooperativity

The reversible transformations between ketones and alcohols via sequential hydrogenation–dehydrogenation reactions are efficiently achieved using a single precatalyst HRu­(bMepi)­(PPh3)2 (bMepi = 1,3-bis­(6′-methyl-2′-pyridylimino)­isoindolate). The catalytic mechanism of HRu­(bMepi)­(PPh3)2 mediated acceptorless alcohol dehydrogenation (AAD) has been investigated by a series of kinetic and isotopic labeling studies, isolation of intermediates, and evaluation of Ru­(b4Rpi)­(PPh3)2Cl (R = H, Me, Cl, OMe, OH) complexes. Two limiting dehydrogenation scenarios are interrogated: inner-sphere β-H elimination and outer-sphere bifunctional double hydrogen transfer. Isotopic labeling experiments demonstrated that the proton and hydride transfer in a stepwise manner. Catalyst modifications suggest that the imine group on the bMepi pincer scaffold is not necessary for catalytic alcohol dehydrogenation. Evaluation of the kinetic experiments and catalyst modifications suggests a pathway whereby HRu­(bMepi)­(PPh3)2 operates via the inner-sphere β-H elimination mechanism. Following a single PPh3 dissociation, an alcohol substrate can bind and undergo proton transfer followed by a turnover-limiting β-H elimination step. Analysis of the Eyring plot established activation parameters for the β-H elimination reaction as ΔH⧧ = 15(1) kcal/mol and ΔS⧧ = −41(3) eu. AAD reactions using a series of Ru­(b4Rpi)­(PPh3)2Cl complexes indicated that the ortho-substituted methyl groups of bMepi slightly impede catalytic activity, and electronic modifications of the pincer scaffold have a minimal effect on the reaction rate.