Use of native and derivatized cyclodextrin chiral stationary phases for the enantioseparation of aromatic and aliphatic sulfoxides by high performance liquid chromatography

Summary The enantioselectivity of native and derivatized cyclodextrin stationary phases for aromatic and aliphatic chiral sulfoxides was evaluated using high performance liquid chromatography (HPLC). Many sulfoxide enantiomers could be baseline resolved using the derivatized cyclodextrin stationary phases in the reverse phase mode. The most important factor influencing enantioselectivity is the presence of steric bulk alpha to the chiral center. However, substituents on an aromatic ring bonded to the sulfoxide have less pronounced effects on enantioselectivity. The 2,3-dimethyl β-cyclodextrin exhibits the broadest anantioselectivity for neutral chiral sulfoxides. Native cyclodextrins and hydroxypropyl-β-cyclodextrins were much less effective in separating this class of molecules. The hydrogen bonding ability of the organic modifier does not significantly affect enantioselectivity.     

Adsorption of water on reconstructed rutile TiO2(011)-(2 x 1): Ti=O double bonds and surface reactivity

Recent combined experimental and theoretical studies (Beck et al., Phys. Rev. Lett. 2004, 93, 036104) have provided evidence for Ti=O double-bonded titanyl groups on the reconstructed rutile TiO(2)(011)-(2 x 1) surface. The adsorption of water on the same surface is now investigated to further probe the properties of these groups, as well as to confirm their existence. Ultraviolet photoemission experiments show that water is adsorbed in molecular form at a sample temperature of 110 K. At the same time, the presence of a 3sigma state in the photoemission spectra and work function measurements indicate a significant amount of hydroxyls within the first monolayer of water. At room temperature, scanning tunneling microscopy (STM) suggests that dissociated water is present, and about 30% of the surface active sites are hydroxylated. These findings are well explained by total energy density functional theory calculations and Car-Parrinello molecular dynamics simulations for water adsorption on the titanyl model of TiO(2)(011)-(2 x 1). The theoretical results show that a mixed molecular/dissociative layer is the most stable configuration in the monolayer regime at low temperatures, while complete dissociation takes place at 250 K. The arrangement of the protonated mono-coordinated oxygens in the mixed molecular/dissociated layer is consistent with the observed short-range order of the hydroxyls in the STM images.     

Probing enantioselectivity on chirally modified Cu(110), Cu(100), and Cu(111) surfaces

Temperature programmed desorption methods have been used to probe the enantioselectivity of achiral Cu(100), Cu(110), and Cu(111) single crystal surfaces modified by chiral organic molecules including amino acids, alcohols, alkoxides, and amino-alcohols. The following combinations of chiral probes and chiral modifiers on Cu surfaces were included in this study: propylene oxide (PO) on L-alanine modified Cu(110), PO on L-alaninol modified Cu(111), PO on 2-butanol modified Cu(111), PO on 2-butoxide modified Cu(100), PO on 2-butoxide modified Cu(111), R-3-methylcyclohexanone (R-3-MCHO) on 2-butoxide modified Cu(100), and R-3-MCHO on 2-butoxide modified Cu(111). In contrast with the fact that these and other chiral probe/modifier systems have exhibited enantioselectivity on Pd(111) and Pt(111) surfaces, none of these probe/modifier/Cu systems exhibit enantioselectivity at either low or high modifier coverages. The nature of the underlying substrate plays a significant role in the mechanism of hydrogen-bonding interactions and could be critical to observing enantioselectivity. While hydrogen-bonding interactions between modifier and probe molecule are believed to induce enantioselectivity on Pd surfaces (Gao, F.; Wang, Y.; Burkholder, L.; Tysoe, W. T. J. Am. Chem. Soc. 2007, 129, 15240-15249), such critical interactions may be missing on Cu surfaces where hydrogen-bonding interactions are believed to occur between adjacent modifier molecules, enabling them to form clusters or islands.     

Adsorption and reaction of cyclohexene on a Ni(111) surface

We studied the adsorption and reaction of cyclohexene (C6H10) on Ni(111) at different temperatures with high-resolution in-situ X-ray photoelectron spectroscopy (HR-XPS). For exposure at 125 K, we find intact cyclohexene with two distinct C 1s signals at 283.3 and 284.2 eV, due to the nonequivalent carbon atoms in the molecule. The energetic separation is significantly increased relative to the gas-phase value, due to the interaction with the substrate. Upon exposure at 210 K, complete dehydrogenation of cyclohexene to benzene (C6H6) and hydrogen is observed; coverage-dependent changes of the benzene adsorption site occur in a way similar to those for pure benzene layers, which indicates a phase separation in benzene and hydrogen islands. The thermal evolution of the adsorbed layers was studied by temperature-programmed (TP-) XPS and temperature-programmed desorption spectroscopy (TPD). Upon heating, the benzene + hydrogen layer formed at 210 K shows a coverage-dependent reorientation of the benzene molecules during partial desorption. The cyclohexene layer adsorbed at 125 K only shows partial conversion of cyclohexene to benzene and hydrogen upon heating to 185 or 210 K, with the remaining cyclohexene being stable up to approximately 300 K. We propose that upon heating these molecules are stabilized by coadsorbed benzene and hydrogen; furthermore, the mobility of benzene and hydrogen in this coadsorbed layer is reduced, so that no phase separation can occur.     

Comparison of the chiral resolution on cis-trans isomeric chiral stationary phases derived from (S)-1-(1-naphthyl)ethylamine

A pair of cis-trans isomeric chiral stationary phases (CSPs) derived from (S)-1-(1-naphtyl)ethylamine was prepared. The chromatographic behaviours on both CSPs with regard to the resolution of enantiomeric amino acids, amino alcohols, amines, and carboxylic acid were studied. According to separation factors, the trans-CSP showed better chiral recognition ability for the separation of most analytes chosen in this study. Three homologous series of the alkyl esters of racemic amino acids were resolved on both CSPs using n-hexane-2-propanol and n-hexane-dichloromethane as mobile phases. The trans-CSP also showed better enantioselectivity for the resolution of homologues. A reverse of elution order was observed for the resolution of the homologous series of phenylglycine alkyl esters on both CSPs. It was found that the relationship between the separation factor and the alkyl chain length of the ester homologous series depended upon the components of mobile phase. A higher magnitude of difference between the two CSPs in enantioselectivity for the resolution of a given homologue was obtained when n-hexane-dichloromethane was used as a mobile phase. A chiral recognition process, in which steric repulsion, face-to-face π-π interaction, face-to-edge π-π interaction and hydrogen bonding interaction were involved, was also suggested to describe the separation of enantiomeric homologues on both CSPs. This study clearly indicates that the chiral resolution is influenced by the geometry of the double bond in a CSP.     

Preparation of a new chiral stationary phase for HPLC based on the (R)- 1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides

A novel chiral stationary phase (CSP) for HPLC was prepared by bonding (R)-1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine to aminopropyl silica gel through a 2-amino-3,5-dinitro-1-carboxamido-benzene unit. The CSP was used for the separation of some amino acid derivatives and pyrethroid insecticides by chiral HPLC. Satisfactory baseline separation required optimization of the variables of mobile phase composition. Use of dichloromethane as modifier in the mobile phase gave baseline separations of amino acid derivatives. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-dichloromethane-ethanol as mobile phase. The results show that the enantioselectivity of the new CSP is better than Pirkle type 1-A column for these compounds. Only partial separations were observed for the stereoisomers of cypermethrin and cyfluthrin, which gave even and eight peaks, respectively.     

Enantiomeric separation of chiral pesticides by high-performance liquid chromatography on an amylose tris-(S)-1-phenylethylcarbamate chiral stationary phase

Amylose tris-(S)-1-phenylethylcarbamate chiral stationary phase (CSP) was prepared. The direct enantiomeric separation of chiral pesticides on this CSP had been studied by HPLC. The mobile phase was n-hexane-isopropanol at a flow rate of 1.0 mL/min. The effects of isopropanol content and column temperature on retention and enantioselectivity were investigated. Thirty-two samples were tested, of which ten interacted enantioselectively with the CSP. Five samples were completely resolved and another five underwent near-baseline or partial resolution. The enantiomers were identified by a circular dichroism detector. Linear van't Hoff plots were established and the thermodynamic parameters were thus calculated.     

外消旋萘普生酯类在(S,S)-Whelk-O1与CDMPC手性柱上的对映体分离及手性识别机理的比较

在Pirkle型的(S,S)-Whelk-O 1与纤维素衍生物型的CDMPC两种手性柱上对六种 外消旋萘普生酯进行了对映体分离，通过研究烷氧基结构上的差异以及流动相中不 同的醇类添加剂对手性识别的影响，探讨和比较了外消旋萘普生酯在两种手性固定 相上手性识别的机理。对于 (S,S)-Whelk-O 1， 溶质与固定相之间的吸引作用于 手性识别的主要因素，而对于CDMPC，溶质在手性空腔中的空间适应性很可能是手 性识别的关键。     

Adsorption of atomic hydrogen on ZnO(1010): STM study

The adsorption of atomic hydrogen on a single crystal ZnO(1010) surface has been studied by scanning tunneling microscopy (STM) under ultrahigh vacuum conditions at room temperature and at elevated temperatures. High resolution STM images indicate that a well-ordered (1x1) H adlayer is formed on the ZnO(1010) surface. The STM data strongly indicate that the hydrogen adsorbs on top of the oxygen atoms forming hydroxyl species. Scanning tunneling spectroscopy (STS) studies reveal a H atom induced metallization at room temperature. In contrast to the clean surface for the hydrogen-covered surface distinct defects structures consisting of missing O and Zn atoms could be identified.     

New insight brought by density functional theory on the chemical state of alaninol on Cu(100): energetics and interpretation of x-ray photoelectron spectroscopy data

In recent years, an increasing interest has been focused on the adsorption of molecules on surfaces due to the importance of technologies based on the interaction of organic systems with metals and oxides for biosensors, catalysis, and molecularly imprinted polymer technology. A particularly attractive area is the study of chiral surfaces, as these can act as heterogeneous catalysts and sensors in the stereochemical industrial processes. This work reports on an ab initio simulation of chemisorption of the D-alaninol on Cu (100). This system has been investigated systematically by using the Vienna ab initio simulation Package (VASP) which performs density functional theory (DFT) calculations in periodic boundary conditions. Molecular dynamics at 300 K is performed to explore all the possible geometries, finally, optimized at 0 K to obtain the adsorption modes. C 1s, O 1s, and N 1s, core level shift (CLS) calculations of those adsorption modes have been evaluated and compared with x-ray photoelectron spectroscopy experimental data. Energetic and CLS indicate that both chemical functions, the NH(2) and the dehydrogenated hydroxyl, are involved in the bonding to the surface at low coverage. Atomic hydrogen coadsorbs in a fourfold hollow site. An atomistic thermodynamics approach suggests that at room temperature under UHV conditions, coadsorbed hydrogen has recombined as H(2) and desorbed from the surface.     

Rhodium-catalyzed asymmetric 1,4-addition of organoboron reagents to 5,6-dihydro-2(1H)-pyridinones. Asymmetric synthesis of 4-aryl-2-piperidinones

Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)-pyridinones in the presence of a chiral bisphosphine-rhodium catalyst. In the reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and 1 equiv (to boron) of water at 40 degrees C gave the highest yield of the arylation product with high enantioselectivity (98% ee). The (R)-4-(4-fluorophenyl)-2-piperidinone obtained here is a key intermediate for the synthesis of (-)-Paroxetine.     

Chiral separations of pesticide enantiomers by high-performance liquid chromatography using cellulose triphenylcarbamate chiral stationary phase

The direct chiral separations of pesticide enantiomers by high-performance liquid chromatography by applying self-prepared cellulose triphenylcarbamate chiral stationary phase are performed. The mobile phase is n-hexane modified by isopropanol as a polar modifier. Nine chiral pesticides (benalaxyl, vinclozolin, diclofop-methyl, tebuconazole, quizalofop-ethyl, hexaconazole, lactofen, isocarbophos, and paclobutrazol) show enantioselectivity on the chiral stationary phase. An online circular dichrorism detector is used for identifying the pesticide enantiomers. The influences of the volume content of isopropanol and column temperature on the separations are investigated. The thermodynamic parameters related to the chiral distinguish mechanisms are also calculated.     

An instance of temperature-dependent elution order of enantiomers from a chiral brush-type HPLC column

Typically, reduction of column temperature increases the enantioselectivity of a chiral stationary phase. An instance in which progressive reduction of temperature initially reduces enantioselectivity, then inverts the elution order of the enantiomers, and finally causes enantioselectivity to increase has been observed. This behavior is related to the nature and concentration of the polar modifier in the mobile phase, and requires particular chiral phase-analyte-mobile phase combinations. A rationalization is presented as to the possible origin of this behavior. This rationale may aid in finding other examples of this temperature-dependent elution order of enantiomers and ultimately increase our understanding of chiral recognition processes.     

Application of (1S,2S)- and (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate to the indirect enantioseparation of racemic proteinogenic amino acids

The application of (1S,2S)- or (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate as a new chiral derivatizing agent for the resolution of compounds possessing an amino group is described. The reagent is easily accessible in both enantiomeric forms after a simple two-step synthesis. Its applicability was demonstrated on the example of the resolution of a series of alpha-amino acids. The diastereomeric thiourea derivatives produced were separated by reversed-phase high-performance liquid chromatography. The effects of pH, temperature and reagent excess on the derivatization kinetics were investigated, as were the effects of pH and organic modifier on the separation.     

Recoverable (R)- and (S)-binap-Ag(I) complexes for the enantioselective 1,3-dipolar cycloaddition reaction of azomethine ylides

The first enantioselective 1,3-dipolar cycloaddition reaction of amino acid derived azomethine ylides and maleimides catalyzed by very stable and recyclable chiral (R)- or (S)-binap-AgClO(4) complexes is described. The reactions are performed at room temperature, in good yields, with high endo diastereoselectivity and enantioselectivity, the complex being recovered by simple filtration.     

Tautomer selective photochemistry in 1-(tetrazol-5-yl)ethanol

A combined matrix isolation FTIR and theoretical DFT/B3LYP/6-311++G(d,p) study of the molecular structure and photochemistry of 1-(tetrazol-5-yl)ethanol [1-TE] was performed. The potential energy surface landscapes of the 1H and 2H tautomers of the compound were investigated and the theoretical results were used to help characterize the conformational mixture existing in equilibrium in the gas phase prior to deposition of the matrices, as well as the conformers trapped in the latter. In the gas phase, at room temperature, the compound exists as a mixture of 12 conformers (five of the 1H tautomer and seven of the 2H tautomer). Upon deposition of the compound in an argon matrix at 10 K, only three main forms survive, because the low barriers for conformational isomerization allow extensive conformational cooling during deposition. Deposition of the matrix at 30 K led to further simplification of the conformational mixture with only one conformer of each tautomer of 1-TE surviving. These conformers correspond to the most stable forms of each tautomer, which bear different types of intramolecular H-bonds: 1H-I has an NH···O hydrogen bond, whereas 2H-I has an OH···N hydrogen bond. Upon irradiating with UV light (λ > 200 nm), a matrix containing both 1H-I and 2H-I forms, an unprecedented tautomer selective photochemistry was observed, with the 2H tautomeric form undergoing unimolecular decomposition to azide + hydroxypropanenitrile and the 1H-tautomer being photostable.     

High-pressure (1 Torr) scanning tunneling microscopy (STM) study of the coadsorption and exchange of CO and NO on the Rh(111) crystal face

The coadsorption of CO and NO on Rh(111) at room temperature was studied with scanning tunneling microscopy (STM) in the catalytically relevant range of approximately 1 Torr. For gas mixtures where NO is not in large excess, a mixed layer with (2x2) structure is formed. The difference in binding energy between CO and NO on top sites was determined from the measured surface (by direct counting in STM images) and gas mole fractions of each species. A model for the molecular structure is proposed based on the analysis of exchange events between CO and NO molecules in the images. In this model as the partial pressure of NO increases, NO molecules occupy hollow sites first, by displacing CO, and top sites later, where they coexist with CO. As the surface fraction of NO increases, favorable NO-NO interactions cause the formation of segregated NO-rich regions. As with pure NO, a phase transition from the (2x2)-NO to the (3x3)-NO structure takes place in the NO-rich regions at high NO concentration. These results demonstrate the unique ability of STM to obtain molecular-level information under catalytic pressure conditions.     

Asymmetric Reduction of Acetophenones with NaBH4 in the Presence of Mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin Tosylate

The asymmetric reduction of acetophenone and its derivatives was achieved with sodium borohydride utilizing a novel chiral ionic liquid of β-cylclodextrin (CD), mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin tosylate (MIM-β-CDOTs). It was found that this chiral β-CD-based ionic liquid could provide higher enantioselectivity for the product alcohols. Moreover, the enantioselectivity of the product alcohols was highly dependent on the structure of prochiral ketones, structure of CD and reduction temperature. An erratum to this article can be found at     

Chiral fluoroacetic acid: synthesis of (R)- and (S)-[2H1]-fluoroacetate in high enantiopurity

A two-step synthesis of (R)- and (S)-[²H₁]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from ～38% ee to >95% ee. The improvement in enantioselectivity applied Bio’s methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [²H₁]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S_N2 inversion process, and suppresses a competing non-stereospecific S_N1 reaction course, and as a result significantly improves the stereointegrity of the C–F bond formation. The intermediate [²H₁]-benzyl alcohols, [²H₁]-benzyl fluorides and the product [²H₁]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their ²H NMR spectra in a chiral matrix of poly-γ-benzyl l-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [²H₁]-fluoroacetate were generated with high enantiomeric purity (95% ee).     

Heterogeneous asymmetric reactions: Part 21. Amino acid derived modifiers in the enantioselective hydrogenation of ethyl pyruvate over supported platinum catalyst

New modifiers were prepared from -tryptophane and tested in the enantioselective hydrogenation of ethyl pyruvate over commercial alumina supported platinum catalyst. Most of these molecules induced only low enantiomeric excesses (ee). (S)-3-(1-methyl-indol-3-yl)-2-methylamino-propan-1-ol was found to be the most effective. Using this modifier under mild reaction conditions (1 bar hydrogen pressure, 273 K), enantiomeric excess up to 43% was obtained. Due to the transformation of the modifier evidenced by ESI-MS, a slight increase in hydrogen pressure led to a dramatic drop of enantioselectivity. An interesting inversion of the sense of enantioselectivity was observed in the case of this modifier when the reaction was carried out in acetic acid instead of toluene. A possible explanation for this phenomenon is proposed.