Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction

Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio‐, diastereo‐, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl‐substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks.     

[U(bipy)4]: A Mistaken Case of U0?

After more than 50 years, the synthesis and electronic structure of the first and only reported “U⁰ complex” [U(bipy)₄] ( 1 ) has been reinvestigated. Additionally, its one‐electron reduced product [Na(THF)₆][U(bipy)₄] ( 2 ) has been newly discovered. High resolution crystallographic analyses combined with magnetic and computational data show that 1 and its derivative 2 are best described as highly reduced species containing mid‐to‐high‐valent uranium ligated by redox non‐innocent ligands.     

Design, synthesis and antifungal activity of novel triazole derivatives

Twenty-three 1 -(1H-1,2,4-triazole-1 -y1)-2-(2,4-difluorophenyl)-3-(iV-cycloproyl-N-substituted-amino)-2-propanols were designed and synthesized on the basis of the active site of lanosterol 14α-demethylase. In vitro antifungal activities showed that some of the title compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.     

Oxidative dearomatization of phenols and anilines via lambda(3)- and lambda(5)-iodane-mediated phenylation and oxygenation

Treatment of 2-methylphenols with chloro(diphenyl)-lambda(3)-iodane led to their regioselective dearomatizing 2-phenylation into cyclohexa-2,4-dienone derivatives via a proposed ligand coupling reaction. In the same vein of investigation, treatment of 2-methylanilines with the lambda(5)-iodane 2-iodoxybenzoic acid IBX reagent led to their regioselective dearomatization into previously undescribed ortho-quinol imines.     

A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry

Three standardised, capillary zone electrophoresis-electrospray ionisation mass spectrometry (CZE-ESI-MS) methods were developed for the analysis of six drug candidates and their respective process-related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected background electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 mM ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE-ESI-MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process-related impurities and provided orthogonality with four established high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings.     

Binding,Release and Functionalization of Intact Pnictogen Tetrahedra Coordinated to Dicopper Complexes

The bridging MeCN ligand in the dicopper(I) complexes [(DPFN)Cu₂(μ,η¹ : η¹-MeCN)][X]₂ (X=weakly coordinating anion, NTf₂ ( 1 a ), FAl[OC₆F₁₀(C₆F₅)]₃ ( 1 b ), Al[OC(CF₃)₃]₄ ( 1 c )) was replaced by white phosphorus (P₄) or yellow arsenic (As₄) to yield [(DPFN)Cu₂(μ,η² : η²-E₄)][X]₂ (E=P ( 2 a – c ), As ( 3 a – c )). The molecular structures in the solid state reveal novel coordination modes for E₄ tetrahedra bonded to coinage metal ions. Experimental data and quantum chemical computations provide information concerning perturbations to the bonding in coordinated E₄ tetrahedra. Reactions with N-heterocyclic carbenes (NHCs) led to replacement of the E₄ tetrahedra with release of P₄ or As₄ and formation of [(DPFN)Cu₂(μ,η¹ : η¹-^MeNHC)][X]₂ ( 4 a,b ) or to an opening of one E−E bond leading to an unusual E₄ butterfly structural motif in [(DPFN)Cu₂(μ,η¹ : η¹-E₄^DippNHC)][X]₂ (E=P ( 5 a,b ), E=As ( 6 )). With a cyclic alkyl amino carbene (^EtCAAC), cleavage of two As−As bonds was observed to give two isomers of [(DPFN)Cu₂(μ,η² : η²-As₄^EtCAAC)][X]₂ ( 7 a,b ) with an unusual As₄-triangle+1 unit.     

Structure and properties of dinuclear manganese(III) complexes with pentaanionic pentadentate ligands including alkoxo, amido, and phenoxo donors

Doubly bridged mu-alkoxo-mu-X (X = pyrazolato or acetato) dinuclear MnIII complexes of 2-hydroxy-N-{2-hydroxy-3-[(2-hydroxybenzoyl)amino]propyl}benzamide) (H5L1) and 2-hydroxy-N-{2-hydroxy-4-[(2-hydroxybenzoyl)amino]butyl}benzamide (H5L2), [Mn2(L)(pz)(MeOH)4].xMeOH (1, L = L1, x = 0.5; 2, L = L2, x = 0; Hpz = pyrazole) and [Mn2(L1)(OAc)(MeOH)4] (3), have been prepared, and their structure and magnetic properties have been studied. The X-ray diffraction analysis of 1 (C24.5H34Mn2N4O9.5, triclinic, P, a = 12.2050(7) A, b = 12.7360(8) A, c = 19.2780(10) A, alpha = 99.735(5) degrees , beta = 96.003(4) degrees , gamma = 101.221(5) degrees , V = 2867.6(3) A3, Z = 4), 2 (C25H34Mn2N4O9, triclinic, P, a = 9.4560(5) A, b = 11.0112(5) A, c = 13.8831(6) A, alpha = 90.821(4) degrees , beta = 92.597(4) degrees , gamma = 93.403(4) degrees , V = 1441.29(12) A3, Z = 2), and 3 (C23H32Mn2N2O11, triclinic, P, a = 10.511(5) A, b = 11.713(5) A, c = 13.135(5) A, alpha = 64.401(5) degrees , beta = 74.000(5) degrees , gamma = 66.774(5) degrees , V = 1329.3(10) A3, Z = 2) revealed that all complexes consist of dinuclear units which are further extended into 1D (1 and 3) and 2D (2) supramolecular networks via hydrogen-bonding interactions. Magnetic susceptibility data evidence antiferromagnetic interactions for all three complexes: J = -3.6 cm-1, D approximately 0 cm-1, g = 1.93 (1); J = -2.7 cm-1, D = 0.8 cm-1, g = 1.93 (2); J = -4.9 cm-1, D = 3.8 cm-1, g = 1.95 (3).     

Synthesis of thiometallate complexes and catalytic hydration of acetonitrile

The bimetallic complexes [M(bipy)nS2M′X2], where M=FeII, RuII, NiII or CoII; bipy=2,2′-bipyridine; n=1 or 2; M′=MoVI or WVI and X=O or S, were synthesized using tetrathiometallates and dithiometallates as bidentate ligands. The characterization of the new bimetallic complexes was carried out by standard techniques. The complexes were tested as catalysts in acetonitrile hydrolysis. The reaction products are acetamide and acetic acid, formed by hydrolysis of acetamide. The most active catalysts in the acetonitrile hydrolysis are [Fe(bipy)2S2MoS2], [Ru(bipy)2S2MoS2] and [Co(bipy)2S2WS2], whereas the lowest activity is shown by the nickel complexes. However, the latter exhibit the highest selectivity in acetamide formation. ZINDO semi-empirical calculations were performed in order to explain some of the properties of the complexes. This revised version was published online in June 2006 with corrections to the Cover Date.     

Kinetic study of nickel(II) complexation by pteroylglutamic acid

The kinetics of the complexation of NiII by pteroylglutamic acid have been studied in the 545 ∘C range, the ionic strength (0.6 M) being regulated with KNO3, in the 5.5–7.0pH range, using the stopped-flow method. Under the experimental conditions two processes were observed. The faster process was detected in the millisecond range and is associated with the reaction between NiII and the ligand. The slower is observed within a few seconds. Complementary equilibrium studies were made at 25 ∘C. The results are consistent with the formation of a 1:1 complex between the reactants, and a mechanism is proposed to account for the observed behaviour. Equilibrium constants for the NiII plus pteroylglutamic acid system, as well as activation parameters, are reported. This revised version was published online in June 2006 with corrections to the Cover Date.     

Flow injection system with gas diffusion for the sequential determination of total nitrogen and phosphorus in vegetables

 A flow injection system was developed for the sequential determination of total nitrogen and phosphorus in digests of vegetables using potentiometric and spectrophotometric detection systems, respectively. A tubular ammonium selective electrode with a sensor system composed of nonactin/monactin in tris(2-ethylhexyl) phosphate was used. The selectivity limitations of this electrode were overcome by the inclusion of a gas-diffusion unit in the system that separated ammonium from the rest of the sample matrix and allowed the determination of total nitrogen and phosphorus by the partition of the sample plug between two streams. The results obtained with the developed FIA system were in good agreement with those of the reference methods. Sampling rates from 40 to 60 samples per hour and relative standard deviations below 3.5% were achieved. Received: 17 October 1996/Revised: 21 November 1996/Accepted: 27 November 1996