Half-Sandwich Ruthenium Catalyst Bearing an Enantiopure Primary Amine Tethered to an N‑Heterocyclic Carbene for Ketone Hydrogenation

By using a copper transmetalation reagent [Cu­(Kaibene)₂]­I, the NHC ligand (S,S)-MeNC₃H₂NCHPhCHPhNH₂ “Kaibene” was transferred to ruthenium to make a precatalyst [RuCp*­(Kaibene)­(MeCN)]­(PF₆) (Cp* = 1,2,3,4,5-pentamethyl­cyclopenta­dienyl), 7, in high yield as a mixture of two diastereomers. Under relatively mild conditions (0.02 mol % Ru, 0.16 mol % KOtBu, iPrOH, 50 °C, 25 bar of H₂), this compound catalyzes the hydrogenation of aryl ketones and one alkyl ketone effectively with excellent activity and productivity (TOF up to 48 s^–1, TON up to 10⁴). At higher hydrogenation pressure (46 bar), the catalytic hydrogenation of N-phenyl-benzylimine to the corresponding amine is efficiently achieved. The hydrogenation of prochiral ketones resulted in low ee (35% for 4-chloroacetophenone). NMR spectroscopy was used to observe diastereomeric hydrides RuCp*­(Kaibene)­(H) 13-R/S that were generated by reaction of 7 with H₂ and base in THF-d₈. Complementary DFT studies suggest that either the heterolytic splitting of dihydrogen to form 13-R/S or the hydride transfer to the substrate can be rate-determining depending on the substrate. Experimental and computational results support mechanisms that involve the heterolytic splitting of dihydrogen to the nitrogen of the amide-ligated form of Kaibene in THF or the heterolytic splitting to an outer-sphere alkoxide derived from the product alcohol or 2-PrOH solvent. An unusual feature is the rapid drop in ee of the product alcohol from as high as 60% (R) to 0% in some cases; this might be due to racemization of the Kaibene ligand in THF caused by the strong base or competitive inhibition of one diastereomer of the catalyst by reaction with the product (R)-alcohol.