Asymmetric multicomponent reactions (AMCRs): the new frontier

Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.     

Synthesis, solid-state structure, and bonding analysis of the beryllocenes [Be(C5Me4H)2], [Be(C5Me5)2], and [Be(C5Me5)(C5Me4H)

The beryllocenes [Be(C(5)Me(4)H)(2)] (1), [Be(C(5)Me(5))(2)] (2), and [Be(C(5)Me(5))(C(5)Me(4)H)] (3) have been prepared from BeCl(2) and the appropriate KCp' reagent in toluene/diethyl ether solvent mixtures. The synthesis of 1 is facile (20 degrees C, overnight), but generation of decamethylberyllocene 2 demands high temperatures (ca. 115 degrees C) and extended reaction times (3-4 days). The mixed-ring beryllocene 3 is obtained when the known [(eta(5)-C(5)Me(5))BeCl] is allowed to react with K[C(5)Me(4)H], once more under somewhat forcing conditions (115 degrees C, 36 h). The structures of the three metallocenes have been determined by low-temperature X-ray studies. Both 1 and 3 present eta5/eta1 geometries of the slip-sandwich type, whereas 2 exhibits an almost regular, ferrocene-like, sandwich structure. In the mixed-ring compound 3, C(5)Me(5) is centrally bound to beryllium and the eta(1)-C(5)Me(4)H ring bonds to the metal through the unique CH carbon atom. This is also the binding mode of the eta(1)-ring of 1. To analyze the nature of the bonding in these molecules, theoretical calculations at different levels of theory have been performed on compounds 2 and 3, and a comparison with the bonding in [Be(C(5)H(5))(2)] has been made. As for the latter molecule, energy differences between the eta5/eta5 and the eta5/eta1 structures of 2 are very small, being of the order of a few kcal mol(-1). Constrained space orbital variations (CSOV) calculations show that the covalent character in the bonding is larger for [Be(C(5)Me(5))(2)] than for [Be(C(5)H(5))(2)] due to larger charge delocalization and to increased polarizability of the C(5)Me(5) fragment.     

Rapid and sensitive method for determining free amino acids in honey by gas chromatography with flame ionization or mass spectrometric detection

This paper describes a rapid, sensitive and specific method for determination of free amino acids in honey involving a new reaction of derivatization and gas chromatography (GC) with flame ionization (FID) and mass spectrometric (MS) detection. The method allows the determination of 22 free amino acids in honey samples in a short time: 8 and 5 min for GC-FID and GC-MS, respectively. Quantitation was performed using Norvaline as internal standard, with detection limits ranging between 0.112 and 1.795 mg/L by GC-FID and between 0.001 and 0.291 mg/L by GC-MS in the selected-ion monitoring mode. The method was validated and applied to a set of 74 honey samples belonging to four different botanical origins: eucaliptus, rosemary, orange and heather. The statistical treatment of data shows a correct classification of different origins over 90%.     

Synthesis and Spectroscopic Characterization of New Lead(II) Thiosaccharinates. Molecular Structure of Bis(thiosaccharinato)tetrakis(pyridine)dilead(II) and Thiosaccharinato‐bis(1,10‐phenantroline)lead(II) Thiosaccharinate

Four new lead(II) thiosaccharinate complexes: [Pb(tsac)₂H₂O] (1) (tsac: thiosaccharinate anion), [Pb₂(tsac)₄(py)₄] (2) (py: pyridine), [Pb(tsac)(o‐phen)₂](tsac)·CH₃CN (3) (o‐phen: 1,10‐phenantroline), and [Pb(tsac)₂(bipy)] (4) (bipy: 2,2′‐bipyridine) were prepared. The infrared and electronic spectra as well as the thermal analysis of all the compounds were recorded and discussed. The thiosaccharinate anion acts in three different coordination forms, one of then reported for the first time. The crystal structures of complexes 2 and 3 have been determined by single crystal X‐ray diffractometry. In complex 2 , two monomeric moieties are joined together forming a symmetric bis‐μ‐sulphur bridged dimer by interaction of two lead(II) atoms through the exocyclic sulphur atoms of two thiosaccharinate ligands. The seven‐fold coordination sphere of each lead atom is completed by two pyridine nitrogen atoms and by another sulfur and two nitrogen atoms of the thiosaccharinate anions. In complex 3 , the lead(II) atom is coordinated by four nitrogen atoms of two 1,10‐phenantroline molecules and by the sulfur and nitrogen atoms of one thiosaccharinate ion. The second anion has an electrostatic interaction with the nucleus.     

Ab initio potential energy surface, variational transition state theory, and quasiclassical trajectory studies of the F+CH4-->HF+CH3 reaction

In this work we present a study of the F+CH(4)-->HF+CH(3) reaction (DeltaHdegrees(298 K)=-32.0 kcal mol(-1)) using different methods of the chemical reaction theory. The ground potential energy surface (PES) is characterized using several ab initio methods. Full-dimensional rate constants have been calculated employing the variational transition state theory and using directly ab initio data. A triatomic analytical representation of the ground PES was derived from ab initio points calculated at the second- and fourth-order M?ller-Plesset levels with the 6-311+G(2df,2pd) basis set, assuming the CH(3) fragment to be a 15 a.m.u. pseudoatom in the fitting process. This is suggested from experiments that indicate that the methyl group is uncoupled to the reaction coordinate. A dynamics study by means of the quasiclassical trajectory (QCT) method and employing this analytical surface was also carried out. The experimental data available on the HF internal states distributions are reproduced by the QCT results. Very recent experimental information about the reaction stereodynamics is also borne out by our QCT calculations. Comparisons with the benchmark F+H(2) and analogous Cl+CH(4) reactions are established throughout.     

The Dowd-Beckwith ring expansion: a theoretical study

UB3LYP/6-311++G(d,p) and ROMP2/6-311++G(d,p)//UB3LYP/6-311++G(d,p) calculations including the effect of benzene solvent through the PCM-UAHF method render a concerted mechanism without fragmentation as the most favourable one for the Dowd-Beckwith radical ring expansion of the bromomethyl adduct of methyl cyclopentanone-2-carboxylate to yield methyl cyclohexanone-3-carboxylate. The corresponding concerted TS is a bicyclic alcoxy radical.     

Copper(II) interaction with unstructured prion domain outside the octarepeat region: speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.     

Chemical transformations of 3‐amino‐2‐quinolones

In order to find new antimalarial drugs, an exploration about the chemical properties of the starting compounds 3‐amino‐6‐chloro‐4‐phenyl‐1H‐quinolin‐2‐one ( 1 ) and 3‐amino‐4‐methyl‐1H‐quinolin‐2‐one ( 2 ) was developed. Acylation with acyl chloride, sulfonyl chloride and acetic anhydride were carried out. Despite a previous report [2], when acetyl chloride or acetic anhydride were assayed on 1 , only the diacetyl derivative 7 was obtained. When this compound was heated at reflux temperature in a mixture of acetic acid and acetic anhydride, it was transformed in the oxazoloquinoline 8 . Further reactions of the acyl derivatives with diazomethane afforded 1‐methylated compounds. Compound 2 gave the imine 16 by condensation with 4‐nitrobenzaldehyde.     

Holo- and hemidirected lead(II) in the polymeric [Pb(4)(mu-3,4-TDTA)2(H2O)2]*4H2O complex. N,N,N',N'-tetraacetate ligands derived from o-phenylenediamines as sequestering agents for lead(II)

The coordinating ability of the ligands 3,4-toluenediamine-N,N,N',N'-tetraacetate (3,4-TDTA), o-phenylenediamine-N,N,N',N'-tetraacetate (o-PhDTA), and 4-chloro-1,2-phenylenediamine-N,N,N',N'-tetraacetate (4-Cl-o-PhDTA) (H4L acids) toward lead(II) is studied by potentiometry (25 degrees C, I = 0.5 mol x dm(-3) in NaClO4), UV-vis spectrophotometry, and 207Pb NMR spectrometry. The stability constants of the complex species formed were determined. X-ray diffraction structural analysis of the complex [Pb4(mu-3,4-TDTA)4(H2O)2]*4H2O (1) revealed that 1 has a 2-D structure. The layers are built up by the polymerization of centrosymmetric [Pb4L2(H2O)2] tetranuclear units. The neutral layers have the aromatic rings of the ligands pointing to the periphery, whereas the metallic ions are located in the central part of the layers. In compound 1, two types of six-coordinate lead(II) environments are produced. The Pb(1) is coordinated to two nitrogen atoms and four carboxylate oxygens from the ligand, whereas Pb(2) has an O6 trigonally distorted octahedral surrounding. The lead(II) ion is surrounded by five carboxylate oxygens and a water molecule. The carboxylate oxygens belong to four different ligands that are also joined to four other Pb(1) ions. The selective uptake of lead(II) was analyzed by means of chemical speciation diagrams as well as the so-called conditional or effective formation constants K(Pb)eff. The results indicate that, in competition with other ligands that are strong complexing agents for lead(II), our ligands are better sequestering agents in acidic media.