Expanding the C2-symmetric bicyclo[2.2.1]hepta-2,5-diene ligand family: concise synthesis and catalytic activity in rhodium-catalyzed asymmetric addition

New C2-symmetric bicyclo[2.2.1]hepta-2,5-dienes bearing methyl and phenyl substituents at the 2 and 5 positions were prepared enantiomerically pure through a two-step sequence starting from the readily available bicyclo[2.2.1]hepta-2,5-dione. Due to the instability or volatility of these dienes, their isolation was achieved through the formation of the corresponding stable [RhCl(diene)]2 complexes. These chiral rhodium complexes displayed high activity and enantioselectivity (up to 99% ee) in the rhodium-catalyzed 1,4-addition and 1,2-addition of phenylboronic acid to cyclic enones and N-sulfonylimines, respectively.     

Highly chemoselective formation of aldehyde enamines under very mild reaction conditions

Although ketone enamines are widely used in organic synthesis, aldehyde enamines are rarely employed due to the limitations of their preparation using known methods (need for acid or base, excess of amine, and/or elevated temperature). We have successfully developed rapid and particularly mild condensation conditions (1 h, 0 degrees C, 1.2 equiv of amine) leading to di- and trisubstituted enamines with excellent conversion (84-100%). Remarkably high chemoselectivity was observed with complete discrimination between aldehyde and ketone, among other functional groups positively tested.     

Photophysical properties of ruthenium(II) tris(2,2'-bipyridine) complexes bearing conjugated thiophene appendages

A small series of ruthenium(II) tris(2,2'-bipyridine) complexes has been synthesized in which ethynylated thiophene residues are attached to one of the 2,2'-bipyridine ligands. The photophysical properties depend on the conjugation length of the thiophene-based ligand, and in each case, dual emission is observed. The two emitting states reside in thermal equilibrium at ambient temperature and can be resolved by emission spectral curve-fitting routines. This allows the properties of the two states to be evaluated in both fluid butyronitrile solution and a transparent KBr disk. It is concluded that both emitting states are of metal-to-ligand charge-transfer (MLCT) character, and despite the presence of conjugated thiophene residues, there is no indication for a low-lying pi,pi*-triplet state that promotes nonradiative decay of the excited-state manifold. A key feature of these systems is that the conjugation length imposed by the thiophene-based ligand helps to control the rate constants for both radiative and nonradiative decay from the two MLCT triplet states.     

New insights into the polymerization of methyl methacrylate initiated by rare-earth borohydride complexes: a combined experimental and computational approach

Polymerization of methyl methacrylate (MMA) initiated by the rare-earth borohydride complexes [Ln(BH(4))(3)(thf)(3)] (Ln=Nd, Sm) or [Sm(BH(4))(Cp*)(2)(thf)] (Cp*=eta-C(5)Me(5)) proceeds at ambient temperature to give rather syndiotactic poly(methyl methacrylate) (PMMA) with molar masses M(n) higher than expected and quite broad molar mass distributions, which is consistent with a poor initiation efficiency. The polymerization of MMA was investigated by performing density functional theory (DFT) calculations on an eta-C(5)H(5) model metallocene and showed that in the reaction of [Eu(BH(4))(Cp)(2)] with MMA the borate [Eu(Cp)(2){(OBH(3))(OMe)C=C(Me)(2)}] (e-2) complex, which forms via the enolate [Eu(Cp)(2){O(OMe)C=C(Me)(2)}] (e), is calculated to be exergonic and is the most likely of all of the possible products. This product is favored because the reaction that leads to the formation of carboxylate [Eu(Cp)(2){OOC-C(Me)(=CH(2))}] (f) is thermodynamically favorable, but kinetically disfavored, and both of the potential products from a Markovnikov [Eu(Cp)(2){O(OMe)C-CH(Me)(CH(2)BH(3))}] (g) or anti-Markovnikov [Eu(Cp)(2){O(OMe)C-C(Me(2))(BH(3))}] (h) hydroboration reaction are also kinetically inaccessible. Similar computational results were obtained for the reaction of [Eu(BH(4))(3)] and MMA with all of the products showing extra stabilization. The DFT calculations performed by using [Eu(Cp)(2)(H)] to model the mechanism previously reported for the polymerization of MMA initiated by [Sm(Cp*)(2)(H)](2) confirmed the favorable exergonic formation of the intermediate [Eu(Cp)(2){O(OMe)C=C(Me)(2)}] (e') as the kinetic product, this enolate species ultimately leads to the formation of PMMA as experimentally observed. Replacing H by BH(4) thus prevents the 1,4-addition of the [Eu(BH(4))(Cp)(2)] borohydride ligand to the first incoming MMA molecule and instead favors the formation of the borate complex e-2. This intermediate is the somewhat active species in the polymerization of MMA initiated by the borohydride precursors [Ln(BH(4))(3)(thf)(3)] or [Sm(BH(4))(Cp*)(2)(thf)].     

Chiral discrimination ofN-(dansyl)-dl-amino acids on human serum albumin stationary phase: Effect of a mobile phase modifier

Summary The effect of perchlorate anion as mobile phase modifier on the separation factor, α, forN-(dansyl)-dl-norvaline andN-(dansyl)-dl-tryptophan on a human serum albumin (HSA) column was studied by varying the concentration,c, of the chaotropic agent and the column temperatureT. Gibbs-Helmholtz parameters Δ(ΔH) and Δ(ΔS) between thed andl enantiomers were determined from linear van't Hoff plots of lnα against 1/T. Thermodynamic results indicated that the enhancement of the separation factor observed asc was increased was enthalpically controlled owing to stereoselective H-bonding interactions. Such behavior was used to optimize the chromatographic conditions for separation ofN-(dansyl)-amino acids on HSA.     

Dissociation Channel Dependence on Peptide Size Observed in Electron Capture Dissociation of Tryptic Peptides

Electron capture dissociation (ECD) of a series of five residue peptides led to the observation that these small peptides did not lead to the formation of the usual c/z ECD fragments, but to a, b, y, and w fragments. In order to determine how general this behavior is for small sized peptides, the effect of peptide size on ECD fragments using a complete set of ECD spectra from the SwedECD spectra database was examined. Analysis of the database shows that b and w fragments are favored for small peptide sizes and that average fragment size shows a linear relationship to parent peptide size for most fragment types. From these data, it appears that most of the w fragments are not secondary fragments of the major z ions, in sharp contrast with the proposed mechanism leading to these ions. These data also show that c fragment distributions depend strongly on the nature of C-terminal residue basic site: arginine leads to loss of short neutral fragments, whereas lysine leads to loss of longer neutral fragments. It also appears that b ions might be produced by two different mechanisms depending on the parent peptide size. A model for the fragmentation pathways in competition is proposed. These relationships between average fragment size and parent peptide size could be further exploited also for CID fragment spectra and could be included in fragmentation prediction algorithms.     

Measurements of water vapor isotope ratios with wavelength-scanned cavity ring-down spectroscopy technology: new insights and important caveats for deuterium excess measurements in tropical areas in comparison with isotope-ratio mass spectrometry

The new infrared laser spectroscopic techniques enable us to measure the isotopic composition (δ(18)O and δ(2)H) of atmospheric water vapor. With the objective of monitoring the isotopic composition of tropical water vapor (West Africa, South America), and to discuss deuterium excess variability (d=δ(2)H - 8δ(18)O) with an accuracy similar to measurements arising from isotope-ratio mass spectrometry (IRMS), we have conducted a number of tests and calibrations using a wavelength-scanned cavity ring-down spectroscopy (WS-CRDS) technique. We focus in this paper on four main aspects regarding (1) the tubing material, (2) the humidity calibration of the instrument, (3) the water vapor concentration effects on δ, and (4) the isotopic calibration of the instrument. First, we show that Synflex tubing strongly affects δ(2)H measurements and thus leads to unusable d values. Second, we show that the mixing ratio as measured by WS-CRDS has to be calibrated versus atmospheric mixing ratio measurements and we also suggest possible non-linear effects over the whole mixing ratio range (~2 to 20 g/kg). Third, we show that significant non-linear effects are induced by water vapor concentration variations on δ measurements, especially for mixing ratios lower than ~5 g/kg. This effect induces a 5 to 10‰ error in deuterium excess and is instrument-dependent. Finally, we show that an isotopic calibration (comparison between measured and true values of isotopic water standards) is needed to avoid errors on deuterium excess that can attain ~10‰.     

Racemic N-sulfonyloxaziridines as highly diastereoselective enolate hydroxylating agents: enantioselective synthesis of (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide

A new, highly enantioselective synthesis of (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide, a synthetic fragment of the experimental hepatitis C drug Telaprevir, has been described. Conjugate addition of the enantiomerically pure Davies lithium amide followed by hydroxylation of the in situ generated β-amino enolate was employed for the formation of the required stereogenic centres. Importantly, very high diastereoselectivities can still be achieved in the key-step when the relatively expensive and enantiopure (camphorsulfonyl)oxaziridine hydroxylating agent is replaced by racemic trans-N-sulfonyloxaziridines. Among the tested N-sulfonyloxaziridines the iso-propyl substituted analogue proved to be the ideal choice from an economic viewpoint.     

Thermodynamic and NMR study of aggregation of dodecyltrimethylammonium chloride in aqueous sodium salicylate solution

The complex aggregation processes of dodecyltrimethylammonium chloride (DTAC) have been studied in dilute solutions of sodium salicylate (NaSal) by isothermal titration calorimetry and electrical conductivity at temperatures between 278.15 K and 318.15 K. A structural transformation that was dependent on the concentrations of DTAC and NaSal was observed. The micellization process in dilute solutions of DTAC has been subjected to a detailed thermodynamic analysis and shown to occur at considerably lower critical micelle concentrations than reported for DTAC in water and NaCl solutions. Gibbs free energy, Δ _mic G ^o, and entropy, Δ _mic S ^o, were deduced by taking into account the degree of micelle ionization, β, estimated from conductivity measurements. From the temperature dependence of the enthalpy of micellization, Δ _mic H ^o, the heat capacities of micellization, D_mic c_p^o {\Delta_{{{\rm mic} }}}c_p^o were determined and discussed in terms of the removal of large areas of non-polar surface from contact with water upon micellization. The process is exothermic at all temperatures, indicating, in addition to the hydrophobic effect, the presence of strong interactions between surfactant and salicylate ions. These were confirmed by ¹H NMR spectroscopy and diffusion NMR experiments. Salicylate ions not only interact with the headgroups but also insert further into the micelle core. At c _NaSal/c _DTAC > 2.5, the structural rearrangements occur even at relatively low concentrations of NaSal.