Asymmetric Transfer Hydrogenation of Arylketones Catalyzed by Enantiopure Ruthenium(II)/Pybox Complexes Containing Achiral Phosphonite and Phosphinite Ligands.

A family of complexes of the formula trans-[RuCl2(L)(R-pybox)] (R-pybox = (S,S)-iPr-pybox, (R,R)-Ph-pybox, L = monodentate phosphonite, PPh(OR)2, and phosphinite, L = PPh2(OR), ligands) were screened in the catalytic asymmetric transfer hydrogenation of acetophenone, observing a strong influence of the nature of both the R-pybox substituents and the L ligand in the process. The best results were obtained with complex trans-[RuCl2{PPh2(OEt)}{(R,R)-Ph-pybox}] (2c), which provided high conversion and enantioselectivity (up to 96% enantiomeric excess, e.e.) for the reduction of a variety of aromatic ketones, affording the (S)-benzylalcohols.

Synthesis of Silver(I) and Gold(I) Complexes Containing Enantiopure Pybox Ligands. First Assays on the Silver(I)-Catalyzed Asymmetric Addition of Alkynes to Imines.

Dinuclear complexes [Ag2(CF3SO3){(S,S)-(i)Pr-pybox}2][CF3SO3] (1), [Ag2(R-pybox)2][X]2 [R-pybox = 2,6-bis[4-(S)-isopropyloxazolin-2-yl]pyridine (S,S)-(i)Pr-pybox and X = PF6 (2) and BF4 (3); R-pybox = 2,6-bis[(3aS,8aR)-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-2-yl]pyridine (3aS,3a'S,8aR,8a'R)-indane-pybox and X = CF3SO3 (4)], [Ag2{(S,S)-(i)Pr-pybox}{(3aS,3a'S,8aR,8a'R)-indane-pybox}][CF3SO3]2 (5), and [Ag2(R-pybox)3][X]2 [R-pybox = (3aS,3a'S,8aR,8a'R)-indane-pybox and X = CF3SO3 (10), SF6 (11), and PF6 (12)] as well as mononuclear complexes [Ag(R-pybox)2][X] [R-pybox = (S,S)-(i)Pr-pybox and X = SbF6 (6), PF6 (7), and BF4 (8); R-pybox = (3aS,3a'S,8aR,8a'R)-indane-pybox) and X = BF4 (9)] have been prepared by the reaction of the corresponding silver salts and pybox ligands using the appropriate molar ratio conditions. The first gold(I)/pybox complex [Au6Cl4{(S,S)-(i)Pr-pybox}4][AuCl2]2 (13) has been synthesized by the reaction of [AuCl{S(CH3)2}] and (S,S)-(i)Pr-pybox (1:1 molar ratio) in acetonitrile. The structures of the dinuclear (1, 4, 5, 10, and 11) and mononuclear (6 and 9) silver complexes and the hexanuclear gold complex 13 have been determined by single-crystal X-ray diffraction analysis. These studies have been complemented with a solution-state study by NMR spectroscopy, which included structure elucidation, variable-temperature measurements, and diffusion studies using diffusion-ordered spectroscopy (DOSY; for complexes 1, 4, 10, and 12). Complexes 1, 2, 4, and 10 have been assayed as catalysts in the asymmetric addition of phenylacetylene to N-benzylideneaniline.

Highly enantioselective hydrogenation of N-aryl imines derived from acetophenones by using Ru-pybox complexes under hydrogenation or transfer hydrogenation conditions in isopropanol.

The asymmetric reduction of N-aryl imines derived from acetophenones by using Ru complexes bearing both a pybox (2,6-bis(oxazoline)pyridine) and a monodentate phosphite ligand has been described. The catalysts show good activity with a diverse range of substrates, and deliver the amine products in very high levels of enantioselectivity (up to 99 %) under both hydrogenation and transfer hydrogenation conditions in isopropanol. From deuteration studies, a very different labeling is observed under hydrogenation and transfer hydrogenation conditions, which demonstrates the different nature of the hydrogen source in both reactions.

Antitumor activity of new enantiopure pybox-ruthenium complexes.

New ruthenium complexes containing enantiopure 2,6-bis[4'(R)-phenyloxazolin-2'-il-pyridine] ((R,R)-Ph-pybox), 2,6-bis[4'(S)-isopropyloxazolin-2'-il-pyridine] ((S,S)-(i)Pr-pybox) or 2,6-bis[4'(R)-isopropyloxazolin-2'-il-pyridine] ((R,R)-(i)Pr-pybox) and water soluble 1,3,5-triaza-7-phosphaadamantane (PTA) or N-substituted PTA phosphanes have been synthesized in high yields and fully characterized. The interactions of these compounds with plasmidic DNA and their cytotoxic activity against the human cervical cancer HeLa cell line are reported, pointing out for the first time the different behaviour of ruthenium enantiomers affecting the cell cycle in HeLa tumor cells.

Antitumor activity of new hydridotris(pyrazolyl)borate ruthenium(II) complexes containing the phosphanes PTA and 1-CH3-PTA.

The synthesis and full characterization of new half-sandwich ruthenium(II) complexes containing κ(3)(N,N,N)-hydridotris(pyrazolyl)borate (κ(3)(N,N,N)-Tp) and the water-soluble phosphanes 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]decane (PTA) and 1-methyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane (1-CH(3)-PTA) has been explored. Single crystal X-ray diffraction analysis for complex [RuCl{κ(3)(N,N,N)-Tp}(PMe(2)Ph)(1-CH(3)-PTA)][CF(3)SO(3)]·2NCMe is also reported. DNA binding properties of the ruthenium complexes have been evaluated by mobility shift assay and MALDI-TOF mass spectrometry. The in vitro antitumor activity of these compounds was assessed by examining their ability to inhibit cell proliferation in a number of human cancer cell lines (NCI-H460, SF-268, MCF-7) and non-tumor human umbilical vein endothelial cells (HUVEC). Some of these new compounds show promising cytotoxic activity with IC(50) values in the low micromolar range, and display differential effects on cancer and normal cell growth.

Facile modification of 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]decane phosphanes coordinated to ruthenium(II).

Hydridotris(pyrazolyl)borate (Tp) ruthenium (II) complexes containing new phosphane ligands are described. The new complexes were obtained by electrophilic attack to a coordinated 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]decane (PTA) ligand. Thus, cationic complexes [RuX{kappa(3)(N,N,N)-Tp}(PPh(3))(1-R-PTA)][Y] (X = Cl, R = H (1), CH(2)Ph (4), CH(2)CH=CH(2) (6), CH(2)C[triple bond]CH (8); X = I, R = CH(2)Ph (5), CH(2)CH=CH(2) (7)) and neutral [RuCl{kappa(3)(N,N,N)-Tp}(PPh(3))(1-I(2)-PTA)] (3) have been synthesized and characterized. For complexes [RuI{kappa(3)(N,N,N)-Tp}(PPh(3))(1-R-PTA)][Y] (R = CH(2)Ph, CH(2)CH=CH(2)) an unprecedented formal C-H activation has been observed in alcohols leading to complexes with 1-methyl-4-phenyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane, 4-(2-methoxyethyl)-1-methyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane and 1-methyl-4-[2-(propan-2-yloxi)ethyl]-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane ligands, respectively, and the mechanism explored through deuteriation experiments. The first I(2)-charge transfer compound between I(2) and a nitrogen which belongs to a ligand coordinated to a transition metal, [RuI{kappa(3)(N,N,N)-Tp}(PPh(3))(1-I(2)-PTA)] is described.

Formation of a cyclobutylidene ring: intramolecular [2 + 2] cycloaddition of allyl and vinylidene C=C bonds under mild conditions.

Intramolecular [2 + 2] cycloaddition of two C=C bonds in vinylidene complexes [Ru(eta5-C9H7){=C=C(R)H}(PPh3){kappa1-(P)-PPh2(C3H5)][BF4] affords cyclobutylidene complexes [Ru(eta5-C9H7){kappa2-(P,C)-(=CC(R)HCH2CHCH2PPh2)}(PPh3)][BF4], which can be also obtained by reaction of terminal alkynes with [Ru(eta5-C9H7)(PPh3){kappa3-(P,C,C)-PPh2(C3H5)}][PF6]. The reaction proceeds under mild conditions via vinylidene complexes, and the activation parameters were determined by kinetic studies.