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

Abstract

The cyclometalated acetate ruthenium complexes [Ru(C^N)(η²-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(η²-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)(η²-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 μM.