The preparation of a series of half-sandwich ruthenium complexes, [RuCl2(η6-p-cymene)(P)] (P* = S-PMeRR′) and [RuCl2(κ-P-η6-arene)], containing P-stereogenic phosphines is reported. The borane-protected P-stereogenic phosphines have been obtained by addition of the (H3B)PMe 2R (R = t-Bu (1), Cy (2), Fc (3))/sec-BuLi/(-)-sparteine adduct to benzyl halides, carbonyl functions, and epoxides with yields between 40 and 90% and ee values in the 70-99% range. Those containing an aryl secondary function have been used in the preparation of [RuCl2(η6-p- cymene)(P)] complexes. Borane deprotection has been performed using HBF 4, except for (H3B)PRMe(CH2SiMe2Ph) phosphines, where DABCO was used to avoid partial cleavage of the CH 2-Si bond. In the case of (H3B)P(t-Bu)Me(CH 2C(OH)Ph2) (1l) the dehydrated phosphine was obtained. The tethered complexes were obtained by p-cymene substitution in chlorobenzene at 120 C, except for ferrocenyl-containing complexes, which decomposed upon heating. The presence of substituents in the aryl arm of some of the phosphines introduces new chiral elements in the tethered [RuCl2(κ-P- η6-arene)] compounds. Full characterization of all compounds both in solution and in the solid state has been carried out. Crystal structure determinations of four phosphine-borane molecules confirm the S configuration at the phosphorus atom (1a,e,l and 2d). Moreover, the crystal structure of one p-cymene complex (5i) and four tethered complexes reveal the strain of the compounds with two atoms in the tether (7c,g,l and 8i). Tethering has a marked effect on the catalytic performance transfer hydrogenation of acetophenone and on the nature of hydridic species originating during the activation period. The chiral induction attains 58% ee with complexes with the bulkiest substituents in the pendant arm of the phosphine. Three of the prepared complexes can interact with DNA and present a reasonable cytotoxicity toward cancer cells. Intercalation of the free aromatic pendant arm of the phosphines seems to be fundamental for such interactions. © 2013 American Chemical Society.