Redox reactions in palladium catalysis: on the accelerating and/or inhibiting effects of copper and silver salt additives in cross-coupling chemistry involving electron-rich phosphine ligands.

Challenging a catalytic cycle: Pd(0) catalysts are readily oxidized by Cu and Ag salts to give dinuclear Pd(I) complexes and Cu(I) or Ag(I) cubanes (see scheme). The reactivities of the resulting Pd(I) dimers are consistent with several observations of additive effects in cross-coupling chemistry. The results indicate the possibility for alternative catalytic cycles involving dinuclear Pd(I) complexes over the currently accepted synergistic cycles involving Pd(0)/Pd(II) intermediates and Cu or Ag.

Reactivity and stability of dinuclear Pd(I) complexes: studies on the active catalytic species, insights into precatalyst activation and deactivation, and application in highly selective cross-coupling reactions.

The catalysis derived from the dinuclear Pd(I)-Pd(I) complex, {[PtBu(3)]PdBr}(2), has been studied with experimental, computational, and spectroscopic techniques. Experimental selectivity studies were performed, and the reactivity was subsequently investigated with density functional theory (B3LYP-D and M06L) to deduce information on the likely active catalytic species. The reactivity with aryl chlorides and bromides was found to be inconsistent with direct catalytic involvement of the Pd(I) dimer but consistent with mononuclear Pd(0) catalysis. Computational studies suggest that precatalyst transformation to the active catalytic species does not proceed via a direct disproportionation mechanism; a reductive pathway is the most likely scenario instead. Through (31)P NMR investigations it was identified that the combination of ArB(OH)(2), KF, and water triggers the conversion of the precatalyst to Pd(PtBu(3))(2) and, most likely, Pd-black as a competing side process, explaining the incomplete conversions of aryl chlorides in Suzuki cross-coupling reactions under Pd(I) dimer conditions. New applications in highly regio- and chemoselective transformations in short reaction times at room temperature are also demonstrated.

Solvent effect on palladium-catalyzed cross-coupling reactions and implications on the active catalytic species.

Suzuki coupling of the bifunctional substrate 1 using [Pd(2)(dba)(3)]/PtBu(3) gives selectivity for C-Cl in nonpolar solvents but for C-OTf in polar solvents. The results of computational and experimental studies suggest that the catalytically active species in polar solvents under conditions employing coordinating additives is inconsistent with monoligated [Pd(PtBu(3))]. Instead, the data are consistent with an anionic palladium complex as the active species.

Simple di- and trivanillates exhibit cytostatic properties toward cancer cells resistant to pro-apoptotic stimuli.

A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.