Variations on an NHC Theme: Which Features Enhance Catalytic Transfer Hydrogenation with Ruthenium Complexes?

N-heterocyclic carbene (NHC) based ruthenium complexes were studied as catalysts for the transfer hydrogenation of ketones. Variations in the catalyst structure were investigated for their impact on hydrogenation and catalyst stability. Catalyst attributes included bis- or mono-NHC ligands, pendant ether groups in some cases, and arene ligands of varied bulk and donor strength. Ruthenium complexes were synthesized and fully characterized, including complexes with a monodentate NHC ligand containing a tethered ether N substituent (ImEt,CH2CH2OEtRuCl2(η6-arene); arene = benzene (4), p-cymene (5), hexamethylbenzene (6)), a complex with a monodentate NHC ligand with solely alkyl N substituents (ImEt,PentylRuCl2(η6-p-cymene) (8)), and a complex with a bis-NHC ligand ([RuCl(methylenebis(ImEt)2)(η6-p-cymene)]PF6 (7)) (Im = imidazole-derived NHC; superscripts indicate N substituents). X-ray crystal structures were obtained for 4, 5, 7, and 8. All of the ruthenium complexes were tested and found to be active transfer hydrogenation catalysts for the reduction of acetophenone to 1-phenylethanol in basic 2-propanol. Precatalyst 4, which contains a tethered ether group and benzene ligand, was found to be the most active catalyst. Variable-temperature 1H NMR studies of complexes 4–6 show that arene lability increases in the order C6Me6 < cymene < benzene, and this lability is directly correlated with catalytic activity. The catalysis appears to be homogeneous, and a mechanism invoking arene loss is proposed. Precatalyst 4 reduced electron-deficient ketones most easily, and 4′-nitroacetophenone was reduced under base-free conditions. The highest TOF (turnover frequency) and TON (turnover number) values obtained were 3003 h–1 and 845, respectively, for ketone reduction with catalyst 4.