In the present study, the potential anti-neoplastic properties of a series of ruthenium half-sandwich complexes of formula [Ru­(η6-arene)­Cl2(PR1R2(1-pyrenyl))] (η6-arene = p-cymene and R1 = R2 = methyl for 1; η6-arene = methylbenzoate and R1 = R2 = methyl for 2; η6-arene = p-cymene and R1 = R2 = phenyl for 3; η6-arene = methylbenzoate and R1 = R2 = phenyl for 4; η6-arene = p-cymene, R1 = methyl and R2 = phenyl for 5; η6-arene = methylbenzoate, R1 = methyl and R2 = phenyl for 6) have been investigated. The six structurally related organoruthenium­(II) compounds have been prepared in good yields and fully characterized; the X-ray structures of three of them, i.e., 1, 2, and 4, were determined. Although the piano-stool compounds contain a large polycyclic aromatic moiety, viz. a 1-pyrenyl group, they do not appear to interact with DNA. However, all the piano-stool complexes show significant cytotoxic properties against five human cell lines, namely, lung adenocarcinoma (A549), melanoma (A375), colorectal adenocarcinoma (SW620), breast adenocarcinoma (MCF7), and nontumorigenic epithelial breast (MCF10A), with IC50 values in the micromolar range for most of them. In addition, the most active compound, i.e., 2, induces a remarkable decrease of cell viability, that is in the nanomolar range, against two human neuroblastoma cell lines, namely, SK-N-BE(2) and CHLA-90. Complexes 1–6 are all capable of inducing apoptosis, but with various degrees of magnitude. Whereas 1, 3, 5, and 6 have no effect on the cell cycle of A375 cells, 2 and 4 can arrest it at the G2/M phase; furthermore, 2 (which is the most efficient compound of the series) also stops the cycle at the S phase, behaving as the well-known anticancer agent cisplatin. Finally, 2 is able to inhibit/reduce the cell migration of neuroblastoma SK-N-BE(2) cells.

The synthesis of enantiopure P-stereogenic diarylphosphines PArPhR (Ar = 9-phenanthryl (a), 1-naphthyl (b), and 2-biphenylyl (c)) with an aryl group at the β (3; R = −CH2CH2­(2-naphthyl)) or γ position (2; R = −CH2Si­(Me2)­CH2Ph)) is described. Treatment of 2a with [RuCl2­(η6-p-cymene)]2 (Dim1) has led to complex [RuCl2­(η6-p-cymene)­(κP-2a)] (4a). Attempts to displace the p-cymene substituent by the pendant aryl group of the phosphine have failed. Reaction of the ligands with [RuCl2(η6-methyl benzoate)]2 (Dim2) has furnished complexes [RuCl2­(η6-methyl benzoate)­(κP-P*)] 6 and 7 (6a–c, P* = 2a–c; 7a–b, P* = 3a–b). The methyl benzoate of 6a and 6b has been successfully replaced by the phenyl ring of the arm of the phosphine, yielding complexes [RuCl2­(κP-η6-phenyl)-P*] (5a and 5b). Unexpectedly, complex 6c has led to tethered [RuCl2­(κP-η6-phenyl)-P­(2-biphenylyl)­PhR] complex (9c), where the coordinated phenyl ring belongs to the 2-biphenylyl group. Reaction of P­(2-biphenylyl)­PhR (R = OMe, Me, i-Pr, and Fc (ferrocenyl)) with Dim2 has given complexes [RuCl2(η6-methyl benzoate)­(κP-P­(2-biphenylyl)­PhR)] (10c–13c). The replacement of methyl benzoate by the phenyl ring of the 2-biphenylyl of the phosphine can be performed at room temperature in the presence of light, giving tethered complexes [RuCl2(κP-η6-phenyl)-P­(2-biphenylyl)­PhR] (14c–17c). Phosphines bearing a substituted 2-biphenylyl group (PArPhR; d (Ar = 2-p-terphenylyl; R = OMe, Me, i-Pr), e (Ar = 2-m-terphenylyl; R = OMe, i-Pr), f (Ar = 2-(1′-naphthyl)­phenyl; R = OMe, i-Pr), and g (Ar = 2-(2′-naphthyl)­phenyl; R = OMe, i-Pr) have been prepared. Phosphines f are present as a mixture of atropisomers. The corresponding Ru complexes have been prepared and subjected to tethering. Tethered complexes with phosphines d are single species in solution, whereas the rest of the phosphines give diastereomeric mixtures with little stereoselection. All complexes have been evaluated in Ru-catalyzed hydrogen transfer of acetophenone in i-PrOH as a solvent obtaining full conversions and up to 47% ee using precursor [RuCl2(κP-η6-phenyl)-P*] (26f, P* = P­(2-(1′-naphthyl)­phenyl)­(OMe)­Ph.

tThe synthesis of five optically pure P-stereogenic monophosphines of the type PPhArR (Ar = 2-pterphenylyl (a), 1-pyrenyl (b); R = OMe, Me, i-Pr) is described. The ligands were fully characterisedand the absolute configurations of PPh(1-pyrenyl)R (3b and 5b; R = OMe and Me respectively) wereconfirmed by X-ray diffraction. The complexation of the monophosphines to Pd and Ru organometal-lic units yielded the neutral complexes [PdCl( 3-2-Me-allyl)P] (10-12) and [RuCl2( 6-pcymene)P](16-18). Complete characterisation, including the crystal structure determination of [RuCl2( 6-p-cymene)(PMePh(2-p-terphenyl))] (17a) is provided. Neutral palladium complexes appeared as mixturesof two diastereomers in solution according to NMR. The synthesis and characterisation of four cationic[Pd( 3-2-Me-allyl)(P)2]PF6(13 and 14) is also described. The application of neutral Pd complexes tocatalytic styrene hydrovinylation afforded moderate conversions, high chemoselectivities (>92%) to 3-phenyl-1-butene and up to 43% ee with precursor 12a. Cationic Pd complexes were tested as catalyticprecursors in allylic substitution of rac-3-acetoxy-1,3-diphenyl-1propene (rac-I), with the anion ofdimethylmalonate and benzylamine as nucleophiles, obtaining full conversions and up to 80% ee in alkyl-ation and 60% ee in amination with precursor 13a. Finally, ruthenium complexes were used as catalyticprecursors in transfer hydrogenation of acetophenone, with complete conversions after several hoursbut low enantioselectivities

The synthesis via phosphine-boranes of 13 new optically pure P-stereogenic diarylphosphines P(Het)PhR (Het = 4-dibenzofuranyl (DBF), 4-dibenzothiophenyl (DBT), 4-dibenzothiophenyl-S,S-dioxide (DBTO2) and 1-thianthrenyl (TA); R = OMe, Me, i-Pr, Fc (ferrocenyl)) following the Jugé-Stephan method is described. The ligands were designed with the aim of having a heteroatom in a position capable of interacting with a metal upon coordination. The ligands and their precursors have been fully characterised, including the determination of two crystal structures of phosphine-boranes. Ru neutral complexes of the type [RuCl2(η(6)-arene)(κP-P)] (arene = p-cymene and methyl benzoate) have been prepared and characterised, including three crystal structure determinations. Treatment of solutions of the complexes with TlPF6 allowed the preparation of well-defined cationic complexes [RuCl(η(6)-arene)(κ(2)P,S-P)]PF6 for DBT- and TA-based phosphines. The complexes possess a stereogenic Ru atom and in most of the cases they are present as a single isomer in solution. All the Ru complexes have been used in the asymmetric transfer hydrogenation of acetophenone in refluxing 2-propanol, with good activities and up to 70% ee.

The coordination chemistry of 13 optically pure P‐stereogenic diarylmonophosphanes P(Het)PhR [Het = 4‐dibenzofuranyl (DBF), 4‐dibenzothiophenyl (DBT), 4‐dibenzothiophenyl S,S‐dioxide (DBTO2) and 1‐thianthrenyl (TA); R = OMe, Me, iPr, Fc (ferrocenyl)] to Pd‐allyl moieties is described. Both neutral [PdCl(η3‐(2‐methylallyl)(κP‐P)] and cationic [Pd{η3‐(2‐methylallyl)(κP‐P)2}]PF6 complexes have been prepared. Coordination of the heteroatom of the heterocycle was only possible in the case of TA‐based phosphanes; these furnished complexes of the type [Pd{η3‐(2‐methylallyl)(κ2P,S‐P)}]PF6 after chloride abstraction with TlPF6. The crystal structure of the complex [Pd(η3‐2‐methylallyl)(κ2P,S‐PPh(OMe)(1‐TA)]PF6 is reported. The neutral Pd complexes were found to be highly active in the hydrovinylation of styrene after activation with AgBF4, except for the TA‐based phosphanes. The cationic Pd complexes were evaluated in allylic alkylation and amination with the model substrate rac‐trans‐1,3‐diphenylprop‐2‐enyl acetate (rac‐I), achieving total conversions and up to 70 % ee.