Mechanistic Investigation of the Hydrogenation of Ketones Catalyzed by a Ruthenium(II) Complex Featuring an N-Heterocyclic Carbene with a Tethered Primary Amine Donor: Evidence for an Inner Sphere Mechanism

The complex [Ru(p-cymene)(m-CH2NH2)Cl]PF6 (1) catalyzes the H-2-hydrogenation of ketones in basic THF under 25 bar of H-2 at 50 degrees C with a turnover frequency (TOF) of up to 461 h(-1) and a maximum conversion of 99%. When the substrate is acetophenone, the TOF decreases significantly as the catalyst to substrate ratio is increased. The rate law was then determined to be rate = k(H)[Ru](tot)[H-2]/(1 + K-eq[ketone]), and [1] is equal to [Ru](tot) if catalyst decomposition does not occur. This is consistent with the heterolytic splitting of dihydrogen at the active ruthenium species as the rate-determining step. In competition with this reaction is the reversible addition of acetophenone to the active species to give an enolate complex. The transfer to the ketone of a hydride and proton equivalent that are produced in the heterolytic splitting reaction yields the product in a fast, low activation barrier step. The kinetic isotope effect was measured using D-2 gas and acetophenone-d(3), and this gave values (k(H)/k(D)) of 1.33 +/- 0.15 and 1.29 +/- 0.15, respectively. The ruthenium hydride complex [Ru(p-cymene)(m-CH2NH2)H]PF6 (2) was prepared, as this was postulated to be a crucial intermediate in the outer-sphere bifunctional mechanism. This is inactive under catalytic conditions unless it is activated by a base. DFT computations suggest that the energy barriers for the addition of dihydrogen, heterolytic splitting of dihydrogen, and concerted transfer of H+/H- to the ketone for the outer-sphere mechanism would be respectively 18.0, 0.2, and 33.5 kcal/mol uphill at 298 K and 1 atm. On the other hand, the energy barriers for an inner-sphere mechanism involving the decoordination of the amine group of the NHC ligand, the heterolytic splitting of dihydrogen across a Ru-O(alkoxide) bond, and hydride migration to the coordinated ketone, are respectively 15.5, 17.5, and 15.6 kcal/mol uphill at 298 K and 1 atm. This is more consistent with the experimental observation that the heterolytic splitting of dihydrogen is the turnover-limiting step. This was confirmed by showing that an analogous complex with a tethered teritiary amine group has comparable activity for the H2-hydrogenation of acetophenone. The related complex [Os(p-cymene)(m-CH2NH2)Cl]PF6 (6) was synthesized by a transmetalation reaction with [Ni(m-CH2NH2)(2)](PF6)(2) (5) and [Os(p-cymene)Cl-2](2), and its catalytic activity toward hydrogenation of acetophen one was also investigated.