New Class of Chiral Diphosphine Ligands for Highly Efficient Transition Metal-Catalyzed Stereoselective Reactions: The Bis(diphenylphosphino) Five-membered Biheteroaryls

The synthesis and application of three examples of a new class of chiral (C(2)) atropisomeric diphosphines characterized by two interconnected five-membered heteroaromatic rings, with hindered rotation around the interanular bond, are described. Optically pure (+)- and (-)-2,2'-bis(diphenylphosphino)-4,4',6,6'-tetramethyl-3,3'-bibenzo[b]thiophene (tetraMe-bitianp) (1a) and the parent unsubstituted system (+)- and (-)-bitianp (1b) were synthesized. They were found to be optically stable at 100 degrees C and were successfully employed as ligands in the Ru(II)-catalyzed hydrogenation of alpha- and beta-oxo esters to the corresponding alpha- and beta-hydroxy esters and in the hydrogenation of olefinic substrates. The optical and chemical yields were comparable with those reported for the same Ru(II)-binap-catalyzed reactions carried out under the same experimental conditions. The 2,2'-bis(diphenylphosphino)-3,3'-bibenzo[b]furan (1c), the oxygenated analogue of bitianp, was found to be configurationally unstable at room temperature. Complete structural X-ray elucidation of the Pd complexes of 1a-c is reported. The advantages of these biheteroaromatic ligands over the classical biaryl systems are discussed.     

Determination of albendazole and its main metabolites in ovine plasma by liquid chromatography with dialysis as an integrated sample preparation technique

Albendazole is a benzimidazole derivative with a broad-spectrum activity against human and animal helminth parasites. In order to determine the main pharmacokinetic parameters in sheep after oral and intravenous administration of a new formulation of albendazole (an aqueous solution), a fully automated method was developed for the determination of this drug and its main metabolites, albendazole sulfoxide (active metabolite) and sulfone in ovine plasma. This method involves dialysis as purification step, followed by enrichment of the dialysate on a precolumn and liquid chromatography (LC). All sample handling operations were executed automatically by means of an ASTED XL system. After conditioning of the trace enrichment column (TEC) packed with octadecyl silica with pH 6.0 phosphate buffer containing sodium azide, the plasma sample, in which a protein releasing reagent (1 M HCl) containing Triton X-100 was automatically added, was loaded in the donor channel and dialysed on a cellulose acetate membrane in the static-pulsed mode. The dialysis liquid consisted of pH 2.5 phosphate buffer. By rotation of a switching valve, the analytes were eluted from the TEC in the back-flush mode by the LC mobile phase and transferred to the analytical column, packed with octyl silica. The chromatographic separation was performed at 35°C and the analytes were monitored photometrically at 295 nm. Due to the differences in hydrophobic character between albendazole and its metabolites, a gradient elution was applied. The mobile phase consisted of a mixture of acetonitrile and pH 6.0 phosphate buffer. The proportion of organic modifier was increased from 10.0 to 50.1% in 12.30 min, then from 50.1 to 66.9% in 1.70 min. First, the gradient conditions and the temperature were optimised for the LC separation using the DryLab software. Then, the influence of some parameters of the dialysis process on analyte recovery was investigated. Finally, the method developed was validated. The mean recoveries for albendazole and its metabolites were about 70 and 65%, respectively. The limits of quantification for albendazole and its metabolites were 10 and 7.5 ng/ml, respectively.     

Convergence of generalized gradients

For the graphs of Clarke's generalized gradients we prove that $$lim sup_{n \to + \infty } gph \partial f_n \subset gph \partial f in (E, strong) \times (E^* , weak).$$ provided that the sequencef _n of locally Lipschitz functions on a Banach spaceE with separable dual is strongly epi-convergent tof, equi-lower semidifferentiable and locally equibounded. This result extends [21] to the infinite-dimensional setting, and finds applications to the continuous behavior of the multiplier rule and of the generalized gradients of integral functionals under data perturbations.     

[2+2] Carbonylative cycloaddition catalyzed by palladium: stereoselective synthesis of β-lactams

[2+2] Carbonylative cycloaddition of chiral imines to various allyl halides, under CO pressure, in the presence of Et₃N, a catalytic amount of Pd(OAc)₂ and PPh₃ as ligand, are carried out. Separable diastereomeric mixtures of chiral alkenyl-β-lactams are isolated with good yields and high trans diastereoselections. Absolute configurations are assigned by X-ray measurements and ¹H NMR spectroscopy.     

Photochemistry of dicyanopyridines

The photochemistry of a variety of dicyanopyridines (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dicyanopyridine) in solution at room temperature was investigated. Pulsed UV (308 nm) laser irradiation in deoxygenated acetonitrile yields the triplet state with lifetimes between 4 and 10 μs and absorption bands in the 400 and 320 nm regions. In the presence of added HCl an air-insensitive transient (τ ≈ 10–12 μs, λ_max ≈ 360–380 nm) was observed, suggesting the formation of a protonated excited state.

Irradiation in the presence of amines resulted in the production of the pyridyl radical anion (τ ≈ 40–80 μs, air sensitive, λ_max ≈ 360–380 nm) formed by electron transfer from the amine to the pyridine triplet excited state. Stern-Volmer analysis gave electron transfer rate constants in the range (1–8) × 10⁻⁸ M⁻¹ s⁻¹.

In methanol solvent, irradiation yielded an air-insensitive transient assigned as the neutral pyridyl radical (τ ≈ 30–200 μs, λ_max ≈ 370–385 nm). The formation of these transients is discussed in the context of previous photochemical electron spin resonance and product studies.     

Steric and Electronic Effects on the Configurational Stability of Residual Chiral Phosphorus‐Centered Three‐Bladed Propellers: Tris‐aryl Phosphane Oxides

A series of tris‐aryl phosphane oxides existing as residual enantiomers or diastereoisomers with substituents on the aryl rings differing in size and electronic properties were synthesized and characterized. Their electronic properties were evaluated on the basis of their electrochemical oxidation and reduction potentials together with those of the corresponding “blade bromides” (i.e., the naphthalene derivatives displaying the same substitution pattern of the tris‐naphthyl phosphane oxide blades, with a bromo substituent where the phosphorus atom is located) determined by CV. The residual stereoisomeric phosphane oxides were isolated in a stereochemically pure state and were found to be highly configurationally stable at room temperature (stereoisomerization barriers of about 27 kcal mol^?1). The chiroptical properties of the residual stereoisomers and the assignments of absolute configuration are discussed. The configurational stability of residual tris‐aryl phosphane oxides was found to be scarcely influenced by the electronic properties of the substituents present on the aromatic rings constituting the blades, while steric effects play the most relevant role. Detailed theoretical calculations are in agreement with the experimental results and also contribute to a rational interpretation of the stereodynamics of these systems.     

Controlling the early stages of pentacene growth by supersonic molecular beam deposition

The key role of the pentacene kinetic energy (Ek) in the early stages of growth on SiOx/Si is demonstrated: islands with smooth borders and increased coalescence differ remarkably from fractal-like thermal growth. Increasing Ek to 6.4 eV, the morphology evolves towards higher density of smaller islands. At higher coverage, coalescence grows with Ek up to a much more uniform, less defected monolayer. The growth, interpreted by the diffusion mediated model, shows the critical nucleus changing from 3 to 2 pentacene for Ek>5-6 eV. Optimal conditions to produce single crystalline films are envisaged.