Cyclometalated CN diphosphine ruthenium catalysts for Oppenauer-type oxidation/transfer hydrogenation reactions and cytotoxic activity

The cyclometalated acetate ruthenium complexes [Ru(C<^>N)(& eta;2-OAc)(dppb)] (dppb = 1,4-bis(diphenylphosphino)butane; HC<^>N = 2-phenylpyridine 1, benzo[h]quinoline 2, 1-phenylpyrazole 3, 2-phenyl-2-oxazoline 4) are easily obtained in 58-74% yield through a one-pot synthesis from [Ru(& eta;2-OAc)2(dppb)] and the corresponding phenyl substituted N-heterocycle in methanol via elimination of HOAc. These complexes have been characterized by single crystal X-ray diffraction studies. Protonation of 2 with HCO2H (5 equiv.) in toluene affords the formate [Ru(C<^>N)(& eta;2-HCO2)(dppb)] (5) isolated in 75% yield, without release of the HC<^>N ligand. The derivatives 1-4 display catalytic activity in the Oppenauer-type oxidation of secondary alcohols to ketones at S/C = 1000, using acetone or cyclohexanone as hydrogen acceptor and KOtBu as base in toluene, with TOF up to 12 000 h-1 for 4. Complexes 1-4 at S/C = 1000 are also active in the TH of carbonyl compounds to alcohols in 2-propanol employing NaOiPr, with TOF up to 14 300 h-1 for 4. The evaluation of the cytotoxic activity of these complexes against U87 glioblastoma cancer cell line via MTT test affords IC50 values ranging from 1.4 to 4.1 & mu;M. The neutral ruthenium cyclometalated complexes [Ru(C<^>N)(& eta;2-OAc)(dppb)] proven to be efficient catalysts in Oppenauer-type oxidation and transfer hydrogenation reactions with TOF up to 14 300 h-1 and show cytotoxic activity against U87 cancer cells.