Ligand-modulated stereo- and regioselective tandem addition reactions of rhenium-bound naphthalene

A series of complexes of the form TpRe(CO)(L)(eta(2)-naphthalene) (Tp = hydridotris(pyrazolyl)borate) undergoes tandem electrophile/nucleophile addition reactions with a high degree of regiocontrol depending on the auxiliary ligand, L. When L = PMe(3), the reaction of the eta(2)-naphthalene complex with triflic acid followed by a silyl ketene acetal favors the 1,4-addition product, whereas when L = pyridine, N,N-dimethylaminopyridine, N-methylimidazole, or NH(3) the 1,2-addition product is favored. These reactions proceed with excellent stereocontrol: both electrophile (H(+), D(+)) and nucleophile (silyl ketene acetal) add anti to the face of metal coordination, and a single coordination diastereomer can be isolated for each reaction. One-electron oxidation of the Re complex affords the corresponding free dihydronaphthalene in good yield.     

Luminol Oxidation by Hydrogen Peroxide Catalyzed by Tobacco Anionic Peroxidase: Steady-State Luminescent and Transient Kinetic Studies

The properties of a newly isolated anionic tobacco peroxidase from transgenic tobacco plants overexpressing the enzyme have been studied with respect to the chemiluminescent reaction of luminol oxidation. These were compared to the properties of horseradish peroxidase in the cooxidation of luminol and p -iodophenol, the enhanced chemiluminescence reaction. The pH, luminol and hydrogen peroxide concentrations were optimized for maximum sensitivity using the tobacco enzyme. The detection limit for the latter under the optimal conditions (2.5 m M luminol, 2 m M hydrogen peroxide, 100 m M Naborate buffer, pH 9.3) was about 0.1 p M , which is at least five times lower than that for horseradish peroxidase in enhanced chemiluminescence with p -iodophenol. The rate constants for the elementary steps of the enzyme-catalyzed reaction have been determined: k ₁= 4.9 × 10⁶ M ⁻¹ s¹, k ₂= 7.3 × 10⁶ M ⁻¹ s⁻¹, k ³= 2.1 × 10⁶ M ⁻¹ s⁻¹ (pH 9.3). The similarity of these rate constants is unusual for plant peroxidases. The high catalytic activity of tobacco peroxidase in the luminescent reaction is explained by the high reactivity of its Compound II toward luminol and the high stability of the holoenzyme with respect to heme dissociation. This seems to be a unique property of this particular enzyme among other plant peroxidases.     

Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders

In this study, the levels and composition of ceramides in brains of newborn mice lacking peroxisomes (Pex5-/-, Zellweger mice) were analyzed using normal-phase high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS). Total ceramide compositions were found to be comparable to that of control animals. However, a minor ceramide species, containing hexacosanoic/hexacosenoic acid as the amide fatty acid, was 9-fold increased. Also, in the sphingomyelin-derived ceramides this species was elevated. Subsequent analysis of extracts from fibroblasts of Pex5-/- mice and mice with a defective peroxisomal beta-oxidation (lacking D-specific multifunctional protein 2 (MFP2)), revealed, again, a similar rise in this particular ceramide. Further, this ceramide was elevated in human X-ALD fibroblasts as well. Whether C26:1/0-ceramide is linked to some of the pathology seen in Zellweger syndrome remains to be investigated. However, an increase in this sphingolipid can be considered as a diagnostic criterion for diseases caused by defects in peroxisome biogenesis or peroxisomal beta-oxidation.     

Relaxation processes in room temperature ionic liquids: the case of 1-butyl-3-methyl imidazolium hexafluorophosphate

A detailed investigation on the nature of the relaxation processes occurring in a typical room temperature ionic liquid (RTIL), namely, 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim][PF(6)]), is reported. The study was conducted using both elastic and inelastic neutron scattering over a wide temperature range from 10 to 400 K, accessing the dynamic features of both the liquid and glassy amorphous states. In this study, the inelastic fixed energy scan technique has been applied for the first time to this class of materials. Using this technique, the existence of two relaxation processes below the glass transition and a further diffusive process occurring above the glass-liquid transition are observed. The low temperature processes are associated with methyl group rotation and butyl chain relaxation in the glassy state and have been modeled in terms of two Debye-like, Arrhenius activated processes. The high temperature process has been modeled in terms of a Kohlraush-Williams-Watts relaxation, with a distinct Vogel-Fulcher-Tamman temperature dependence. These results provide novel information that will be useful in rationalizing the observed structural and dynamical behavior of RTILs in the amorphous state.     

Competing reaction pathways from α-halo-α-protioalkyl aryl sulfoxides initiated by organometallic reagents

The reactions of syn-1-haloethyl p-chlorophenyl sulfoxides (halogen = Cl, Br) with main-group organometallic reagents (n-BuMgCl, MeLi, n-BuLi, s-BuLi, and t-BuLi) in THF and PhMe solvents were examined. Product distributions were analyzed to determine the extent of competing sulfoxide ligand exchange, halogen-metal exchange, and deprotonation reaction pathways. A combination of t-BuLi in PhMe was optimal for initiation of sulfoxide ligand exchange from syn-1-chloroethyl p-chlorophenyl sulfoxide.     

An unusual dichotomy in the regioselectivity of a metal catalyzed versus thermal ene reaction

A Pd(+2) catalyzed cyclization of a 1,6-enyne complements a thermal Alder ene reaction; a rationale invoking a remote binding site is proposed.     

A reinvestigation of asymmetric induction in diels-alder reactions to chiral acrylates.

The chiral induction in the Diels-Alder addition $\text{1}$ → $\text{2}$, assessed reliably by ¹⁹F-NMR-spectroscopy of the endo-esters $\text{4}$, varied between 47 - 93% in favor of the 2-(R)-adducts $\text{2}$ depending on the auxiliary chiral group and the Lewis-acid catalyst.     

Synthesis of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine. Modification of the published structure of propyleine

The total syntheses of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine are described. Evidence that the alkaloid propyleine is actually a rapidly interconverting mixture of propyleine and a previously unknown isomer isopropyleine is presented.     

A novel anthracenyl tagged protecting group for "phase-switching" applications in parallel synthesis

A new "phase-switching" protecting group 1 that facilitates the parallel synthesis of carboxylic acids, esters, and carboxamides is described. Its use permits chemistries to be performed in solution, which may be conveniently monitored with conventional analytical techniques, followed by subsequent immobilization onto a solid-phase support to aid compound purification. Carboxylic acids, esters, and carboxamides are then cleaved from the solid support following activation of the "safety-catch" and treatment with the desired nucleophile.     

One-carbon chain extension of esters to alpha-chloroketones: a safer route without diazomethane

The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 degrees C affords the chain-extended beta-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding alpha-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected alpha-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to alpha-chloroketones that avoids the use of toxic and explosive diazomethane.