Site epimerization in ansa-zirconocene polymerization catalysts

Metallocene alkyl cations for polymerization of olefins possess two active sites involved in migratory insertion. Site epimerization, with an inversion at the metal atom, is considered to be one of the major causes for break-down of the alternating propagation model, resulting in stereoerrors whenever the two catalytic sites have substantially different enantioface selectivities. Density functional theory has been used to determine the intrinsic reaction coordinate that connects the optimized minima and transition states of inversion in the parent ansa-zirconocene [{H₂C(Cp)₂}Zr-Pr]⁺ (Pr = n-propyl). These calculations yield a three-step reaction path for site epimerization. Starting from the pyramidal β-agostic complex, an activated rotation around the Zr-Pr bond first produces an α-agostic conformation. Continued rotation leads to an equivalent second α-agostic intermediate and then finally to the inverted β-agostic complex. The second step is rate-determining and proceeds through a planar three-coordinate transition state. In the case of [{H₂C(Cp)₂}Zr-ⁱBu]⁺ (ⁱBu = iso-butyl), the situation is more complicated, because there are several interconvertible α-, β- and γ-agostic intermediates, but the rate-limiting step is again an inversion process connecting two different α-agostic conformers with the alkyl group on opposite enantiosides. For both ansa-zirconocene catalysts, the computed free-energy barriers for epimerization are around 11-12 kcal/mol and almost independent of temperature, while those for insertion increase with temperature due to the entropic cost of association. According to the computational results for the isolated catalysts, insertion remains favored over epimerization for the experimentally relevant temperature range in the n-propyl case, whereas both processes are competitive in the iso-butyl case. Inclusion of bulk solvent effects by a continuum solvation model does not affect the results much, while explicit consideration of a coordinating counterion causes larger changes. The present model calculations on the role of site epimerization should thus be most relevant for propene polymerization with non-coordinating counterions.     

Synthesis of methoxy-substituted phenols by peracid oxidation of the aromatic ring

[reaction: see text] A novel benign protocol for the preparation of hydroxy-methoxybenzene derivatives is disclosed. By utilizing this protocol, activated aromatic compounds such as 1,3-dimethoxy-2-methyl-benzene and 1-(2,6-dimethoxyphenyl)ethanone are smoothly converted to the corresponding monohydroxylated compound. The reaction can be considered to be a normal aromatic electrophilic substitution reaction, and the regioselectivity for the reaction thus follows the similar rules as for electrophilic substitutions. The protocol is composed by benign reagents, namely, hydogenperoxide, acetic acid, and p-toluene sulfonic acid, which lead to the production of ethaneperoxoic acid in situ. The ethaneperoxoic acid operates as the hydroxylating reagent. The hydroxylation reaction is completed within a short period and requires moreover only mild experimental conditions, which make this novel protocol a green, cheap, and rapid process leading to hydroxy-methoxybenzene derivatives. The proposed reaction mechanism is supported by density functional theory and NMR spectroscopy experiments. The mechanism is constituted by two discrete steps: (a) addition of OH+ to the most nucleophilic carbon atom of the aromatic ring, which is the rate-determining step, and (b) the loss of the proton from the aromatic ring.     

The role of intermediate chain migration in propene polymerization using substituted {iPr(CpFlu)}ZrCl2/MAO catalysts

Comparison of pentad distributions obtained from NMR spectra and from a molecular mechanics‐based modeling approach is performed for the catalysts {ⁱPr(3‐X‐CpFlu)}ZrCl₂ (X = H, Me, Et, ⁱPr, ^tBu) at a range of different temperatures. In order to model the temperature dependency of the pentad distributions the variation in steric influence along with the change of the rotational energy level for catalysts with substituents displaying relatively low barriers to rotation is treated approximately by calculating energy profiles of 360° rotation of the alkyl groups. The temperature at which intermediate chain migration (back‐skip) or chain epimerization starts to be important seems to be rather constant (30–50°C) among the five catalysts. Even in the case of X = ^tBu, back‐skip seems to be unimportant for explaining the formation of isotactic polymer at room temperature.     

Stereoselective Synthesis,Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA

Herein we report the first total synthesis of RvD2_{n-3 DPA}, an endogenously formed mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross-coupling reactions, and a Z-selective alkyne reduction protocol, yielding RvD2_{n-3 DPA} methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2_{n-3 DPA} also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles.     

Computational science in the eighteenth century. Test cases for the methods of Newton,Raphson, and Halley: 1685 to 1745

Numerical Algorithms - This is an overview of examples and problems posed in the late 1600s up to the mid 1700s for the purpose of testing or explaining the two different implementations of the...     

A Facile Formal Synthesis of Volicitin

A short and concise synthesis of volicitin is presented. The synthesis is based on repeated chemoselective copper salt cross coupling reactions of alkynes and propargylic halides.     

Langmuir films of naphthenic acids at different pH and electrolyte concentrations

Langmuir films of naphthenic acids at different pH and electrolyte concentrations are reported. The polydisperse naphthenic acids were commercially available, while two single-component naphthenic acids [5#(H)-cholanoic acid and 1-naphthalenepentanoic acid, decahydro- (9CI)] were synthesized. 1-naphthalenepentanoic acid, decahydro- is too water-soluble to form stable monolayers. 5#(H)-Cholanoic acid and Fluka naphthenic acid form stable films when cations are present in the aqueous subphase. At lower pH the cations are less influential since the naphthenic acids are not protolysed and metal naphthenates cannot be formed. pK_a^s for 5#(H)-cholanoic acid is determined to 5.65. The micellisation of the naphthenates at high pH is described.     

DISTRIBUTION OF 5-AMINOLEVULINIC ACID-INDUCED PORPHYRINS IN NODULOULCERATIVE BASAL CELL CARCINOMA

Abstract— Microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced porphyrins in 22 patients with a total number of 52 noduloul-cerative basal cell carcinomas (BCC) after topical ALA application with or without dimethylsulfoxide (DMSO)/ethylenediaminetetraacetic acid (EDTA) or after intravenous administration of ALA. Both localization patterns and amounts of ALA-induced porphyrins in the BCC were studied. The ALA-induced porphyrins were localized only in the superficial layers of the noduloulcerative BCC lesions after topical application of 20% ALA alone for 3 h. However, both the penetration of ALA into deep lesions and the production of the ALA-induced porphyrin fluorescence were increased after topical administration of 20% ALA and 20% DMSO/4% EDTA for 3 h. Prior treatment with 99% DMSO for 15 min further enhanced the ALA penetration into the BCC lesions after topical application of the ALA/DMSO/EDTA mixture and produced more ALA-induced porphyrins by a factor of about three compared with those treated with ALA alone. The penetration of ALA into the deep BCC lesions could also be increased by prolonging the time of topical application of 20% ALA/4% EDTA to 29–48 h (without DMSO). Intravenous injection of ALA led to a more homogeneous distribution of the ALA-derived porphyrins in the whole noduloulcerative BCC lesions.     

Synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate

The first total synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate has been achieved in seven steps and in 16% overall yield. The synthesis confirmed the assigned structure of this polyunsaturated natural product.