A walk around the A3-coupling

In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A(3)-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A(3)-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A(3)-coupling as well as different tandem reactions involving A(3)-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A(3)-couplings and related transformations.     

Anomeric effect in N-azidomethylpyrrolidine: gas-phase electron diffraction and theoretical study

Gas-phase electron-diffraction data and high-level quantum chemical calculations have been used to study the conformational behaviour of N-azidomethylpyrrolidine. The two most stable conformers with a relative abundance of about 80% at 298 K possess gauche orientation of the azidomethyl group around the C-N(pyr) bond (C-N(azido)gauche with respect to the endocyclic N(pyr)-C bond). This orientation is a strong manifestation of an anomeric effect. The influence of the anomeric effect is also reflected in shortening of the C-N(pyr) bond and lengthening of the C-N(azido) bond as compared to such bonds in other compounds.     

Novel trialkylsilyl(germyl)-substituted thienyl- and furylbenzimidazoles and their N-substituted derivatives – synthesis,structure and cytotoxic activity

The reaction of 1,2-phenylenediamine with a variety of silicon- or germanium-containing 2-furaldehydes or 2-thienylcarbaldehydes in DMFA gave the corresponding benzimidazole derivatives in moderate yields (36–49%) in the presence of sodium hydrogen sulfite. As a result, a new series of silyl, germyl substituted hetarylbenzimidazoles were synthesized and their in vitro cytotoxicity was studied. The quaternisation of N-substituted benzimidazoles by heating with various alkyl, allyl and propargyl chlorides and bromides leads to the formation of benzimidazolinium salts. Potential cytotoxic activity of synthesized new benzimidazoles and benzimidazolinium salts was tested in vitro on two monolayer tumour cell lines: MG-22A (mouse hepatoma), HT-1080 (human fibrosarcoma) and normal mouse fibroblasts (NIH 3T3) and compared with corresponding benzimidazoles.     

Mechanism of white phosphorus activation by three-coordinate molybdenum(III) complexes: a thermochemical, kinetic, and quantum chemical investigation

White phosphorus (P(4)) reacts with three-coordinate molybdenum(III) trisamides or molybdaziridine hydride complexes to produce either bridging or terminal phosphide (P(3)(-)) species, depending upon the ancillary ligand steric demands. Thermochemical measurements have been made that place the MoP triple bond dissociation enthalpy at 92.2 kcal.mol(-)(1). Thermochemical measurements together with computational analysis rule out simple P-atom abstraction from P(4) as a step in the phosphorus activation mechanism. Kinetic measurements made by the stopped-flow method show that the reaction between the monomeric molybdenum complexes and P(4) is first-order both in metal complex and in P(4). Cyclo-P(3) complexes can be obtained when ancillary ligand steric demands are small, but kinetic measurements rule them out as monometallic intermediates in the P(4) activation mechanism. Also studied by calorimetric, kinetic, and in one case variable-temperature NMR methods is the process of mu-phosphide bridge formation. Post-rate-determining steps of the P(4) activation process were examined in a search for minima on the reaction's potential energy surface, leading to the proposal of two plausible, parallel, bimetallic reaction channels.     

Isotopic scrambling in Di-13C-labeled 2-butyl cation: evidence for a protonated cyclopropane intermediate

The (13)C NMR spectrum of 2-butyl-1,2-(13)C(2) cation (1) is unchanged on heating the sample to -78 degrees C, indicating no isomerization to another isotopomer. In contrast, the spectrum of 2-butyl-2,3-(13)C(2) cation (2) shows rapid formation of all of the other isotopomers except 1. These results are consistent with a protonated cyclopropane intermediate in the rearrangement process. In this mechanism, either C(1) and C(2) or C(3) and C(4) interchange. Only the bond between C(2) and C(3) breaks.     

Novel radial oligothienyl silanes

A series of thiophene-based homologues with a silicon core surrounded by mono-, bi-, terthiophene, and their derivatives with alkylsilyl linkages has been prepared using hydrosilylation and Stille coupling methods.     

Evaluation of Free Radical-Scavenging Activity of Sea Urchin Pigments Using HPTLC with Post-Chromatographic Derivatization

Chromatographic separation, analysis of in situ radical-scavenging activity, and quantitative analysis of green sea urchin shell pigments were carried out by online HPTLC-DAD and HPTLC-DPPH methods. Methanol:chloroform:acetic acid:water (11:50:5:2, v/v) was selected as the best mobile phase on silica gel plates for the separation of the pigments. Two pigment spots, S1 and S2, were observed on the TLC plates, while echinochrome A was not detected in the pigment extract of green sea urchin shells. Based on the estimated ID₅₀ values, the antiradical activity was S2 (0.043 μg) > S1 (0.058 μg) > echinochrome A (0.134 μg).     

Synthesis of novel 5-substituted pyrazole derivatives as cannabinoid antagonists

A facile seven-step sequence was developed from 4′-bromopropiophenone, utilizing a Suzuki-type coupling with an alkene, to give several novel 5-substituted pyrazole derivatives in overall yields of 11-31%. They are potent CB1 antagonists and have binding affinities similar to SR 141716A. Like SR 141716A, they may prove to be clinically useful for the treatment of obesity.