(R)-(+)-[VCD(+)945]-4-Ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center

Enantiopure (R)-(+)-[VCD(+)945]-4-ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center, was synthesized by the use of MαNP acid method, and its absolute configuration was first unambiguously determined by the ¹H NMR anisotropy, X-ray crystallography, and VCD methods.     

Dendrimer-Like Chiral Stationary Phases Derived from (1R, 2R)-(+)-1,2-Diphenylethylenediamine and 1,3,5-Benzenetricarbonyl Trichloride

Three dendrimers were synthesized directly on aminated silica gel using (1R, 2R)-(+)-1,2-diphenylethylenediamine and 1,3,5-benzenetricarbonyl trichloride as building blocks. The chiral stationary phases were obtained by modification of these dendrimers with phenyl isocyanate. All derivatives prepared on silica gel were characterized by FTIR spectrum, solid-state ¹H NMR and elemental analysis. The enantioseparation ability of the chiral stationary phases was preliminarily evaluated by high-performance liquid chromatography. The chiral stationary phase of one-generation dendrimer exhibited best enantioseparation ability.     

Proximal heteroalkylation of monoalkoxycalix[4]arenes in synthesis of inherently chiral molecules

Proximal heteroalkylation of monoalkyl ethers of calix[4]arenes or p-tert-butylcalix[4]arenes in NaH/CH₃CN or NaOH/DMSO, respectively, was applied for synthesis of inherently chiral calixarenes with ABHH substitution pattern. The introduction by the method of (R)- or (S)-N-(α-phenylethyl)acetamide chiral auxiliary group gives mixtures of diastereomeric derivatives of inherently chiral calixarenes, which were separated by column chromatography. The chiral calixarenes were thoroughly characterized by ¹H, ¹³C NMR, and X-ray diffraction methods.     

Synthesis and chiral recognition properties of two novel chiral calix[4]arene tartaric ester derivatives

Two new chiral calix[4]arene derivatives containing tartaric acid ester moieties were synthesized. The chiral calix[4]arenes are in a ‘cone’ conformation according to NMR spectroscopy. The chiral recognition capabilities of 1–4 toward the guests, 1,2-propanediol and serine methyl ester hydrochloride (SerOMe), were investigated (¹H NMR spectroscopy). The extraction properties of compounds 1 and 2 toward selected α-amino acid methyl esters were also studied.     

Chiral nitrogen-containing calix[4]crown—an excellent receptor for chiral recognition of mandelic acid

A chiral nitrogen-containing calix[4]crown 2 bearing optically pure 1,2-diphenyl-1,2-oxyamino residue at lower rim showed excellent chiral recognition between enantiomers of mandelic acid. Using competitive ¹H NMR titration the ratio of association constants of (S)- and (R)-mandelic acid with the chiral calix[4]crown was determined to be 102, that is 98% de, which is the best result obtained from artificial receptors for the chiral recognition of mandelic acid up to now.     

Synthesis of novel chiral Schiff base and amino alcohol derivatives of calix[4]arene and chiral recognition properties

In the present study, the synthesis and liquid phase extraction properties towards some amino acid methylesters and amino alcohols of Schiff base and amino alcohol substituted calix[4]arene are reported. The Schiff base substituted calix[4]arene 5 has been synthesized via condensation reaction involving 5,17-diformyl-11,23-di-tert-butyl-25,27-di[3-(4-formylphenoxy)propoxy]-26,28 dihydroxycalix[4]arene 4 and (R)-(?)-2-phenylglycine methyl ester in CHCl₃:MeOH. To give the amino alcohol substituted calix[4]arene 6, the synthesized chiral compound 5 was reduced by LiAlH₄. The new chiral Schiff base and amino alcohol derivatives of calix[4]arene have been characterized by a combination of FT-IR, ¹H NMR, ¹³C NMR, FAB-MS and elemental analysis. Also, the extraction behaviors of 5 and 6 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction.     

trans-Dichlorobis{(1R,4S)-1,7,7-trimethyl-3-[(S)-α-methylbenzylimino]bicyclo[2.2.1]heptan-2-one-N}Palladium(II): Synthesis and structural examination

A reaction of (1R,4S)-1,7,7-trimethyl-3-[(S)-α-methylbenzylimino]bicyclo[2.2.1]heptan-2-one with lithium tetrachloropalladate gave a chiral palladium(II) complex with monodentate coordination of the organic ligand. The structure of the complex was confirmed by NMR spectra and X-ray diffraction data.     

2-aryl(hetaryl)-4H-[1,2,4]triazolo[1,5-a]benzimidazoles

2-(4-Methylphenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole and its previously unknown 2-(2-furyl)- and 2-(2-thienyl)-substituted analogs were synthesized by cyclization of benzimidazole-1,2-diamine with the corresponding carboxylic acid chlorides. The IR, ¹H, ¹³C, and ¹⁵N NMR, and mass spectra of the cyclization products in combination with the results of quantum-chemical calculations of NMR chemical shifts showed radical differences of [1,2,4]triazolo[1,5-a]benzimidazoles having no substituent on N⁴ from the recently reported low-melting products of oxidation of 2-amino-1-arylmethylideneaminobenzimidazoles with (diacetoxy-λ³-iodanyl)benzene, which, as we believe, were erroneously assigned analogous structure.     

Efficient NMR enantiodiscrimination of bridge fluorinated paracyclophanes using lanthanide tris β-diketonate complexes

A selection of amino-substituted 1,1,2,2,9,9,10,10 octafluoro[2.2]paracyclophanes were tested for enantiodiscrimination by ¹H and ¹⁹F NMR spectroscopy via their interaction with different lanthanide tris β-diketonate chiral shift reagents. The amino-, and the pseudo-ortho di-amino substituted octafluoro[2.2]paracyclophanes, both of which exhibit planar chirality, revealed significant shifts and splittings of various ¹H and ¹⁹F NMR signals upon the addition of the chiral shift reagents, which allowed the easy determination of the enantiomeric purity. When the chiral shift reagent was added to an inseparable mixture of the (chiral) pseudo-meta, and (achiral) pseudo-para diamino analogues, both the chiral and achiral molecules revealed NMR doubling. In the case of the achiral molecule, this NMR behavior is due to the meso nature of the pseudo-para species.     

Steric mode of enzymic hydroxylation at primary carbon atoms: Hydroxylation of (1R)- and (1S)-[1-3H, 2H, 1H][1-14C]-octanes by Pseudomonas Oleovorans

(1R)- and (1S) [1-³H, ²H, ¹H]-octanes and mixed with [1-¹⁴C]-octane, were synthesized. The mixed samples were incubated with homogenats of P. oleovorans strain TF4-1L and the biosynthesized mixtures of octanols isolated. It was shown that mainly the achiral termini [-C¹H₃] were hydroxylated and that chiral methyls were oxygenated to the extent of 20–30%. In all instances the products derived from hydroxylation at the chiral methyls [-C-³H, ²H, ¹H] were mixtures of (1R)- and (1S)-octanols, the major component of which was the alcohol obtained by displacement of ¹H. The results indicate that hydroxylation proceeded with a normal isotope effect k_h>k_d>k_t. The amount of (1R)-octanol in the mixtures of octanols derived from (1R)- and (1S)-octane was determined. It was found that the C-1 hydroxylation of octane proceeded with retention, i.e. the incoming hydroxyl assumed the orientation of the displaced hydrogen (or isotopic hydrogen) atom.     

Synthesis of chiral calix[4]arenes bearing tartaric ester moieties

The synthesis of chiral calix[4]arenes with tartaric acid ester moieties has been achieved by the reactions of tartaric ester chloroacetates with calix[4]arenes in moderate yields. All the chiral calix[4]arene derivatives are in a cone conformation according to the ¹H NMR doublet–doublet pattern of the protons of the methylene groups between the phenol rings. The results of NMR and specific rotations indicate that the molecules have C₂ symmetry with asymmetric features.     

Inherently chiral biscalixarene cone–cone conformers consisting of calix[4]arene and calix[5]arene subunits

Inherently chiral biscalixarenes with hetero-cavities were synthesized by a covalent assembly of p-tert-butylcalix[5]arene with a 1,3-substituted calix[4]arene via 1,3-alkylation reaction and subsequent desymmetrization. The racemates were resolved by chiral HPLC method. ¹H NMR spectra, VT-NMR spectra, and theoretical calculations support that the calix[5]arene subunit of the inherently chiral calix[4][5]arene ester adopts a cone-in conformation, with the aromatic ring bearing the CH₂CO₂Et group tilting inward the calix[5]arene cavity. By contrast, such a cone-in structural feature of the calix[5]arene subunit disappears for the corresponding inherently chiral calix[4][5]arene carboxylic acid, due to the intramolecular hydrogen bonding between the carboxyl group and an ethereal oxygen of the glycolic chain.     

Aggregation behavior of imidazolium-based chiral surfactant in aqueous solution

A novel imidazolium-based chiral surfactant with a Y-type hydrophobic chain, (S)-(+)-1-(2,3-bis(octanoyloxy)propyl)-3-methylimidazolium chloride ([Bopmim]Cl), was synthesized. The aggregation behavior of [Bopmim]Cl in aqueous solution was then investigated by surface tension, electrical conductivity, ¹H NMR, and fluorescence measurements. Compared with [C₁₂mim]Cl, the critical micelle concentration for [Bopmim]Cl is lower, indicating that the novel chiral surfactant has superior capacity to form micelles. A larger value of pC ₂₀, a greater minimum area per surfactant molecule (A _min), a smaller degree of counterion binding (β), and a looser aggregate are caused by the relatively larger Y-type hydrophobic chain of [Bopmim]Cl. Furthermore, analysis of the ¹H NMR spectra revealed that the introduced Y-type hydrophobic chain may prevent the hydrophobic group from forming an extended chain configuration and cause a changeover from trans to gauche conformations upon micellization. The micelles of the novel chiral surfactant may provide some potential applications in the stereochemical recognition of surfaces or of biological structures.     

Asymmetric transfer hydrogenation of acetophenone derivatives with novel chiral phosphinite based η-p-cymene/ruthenium(II) catalysts

Enantioselective reduction of prochiral ketones to optically active secondary alcohols is an important subject in synthetic organic chemistry because the resulting chiral alcohols are extremely useful, biologically active compounds. The new chiral ligands (2R)-2-[benzyl{(2-((diphenylphosphanyl)oxy)ethyl)}amino]butyldiphenylphosphinite, 1 and (2R)-2-[benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, 2 and the corresponding ruthenium(II) complexes 3 and 4 have been prepared. The structures of these complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. ³¹P-{¹H} NMR, DEPT, ¹H-¹³C HETCOR or ¹H-¹H COSY correlation experiments were used to confirm the spectral assignments. These ruthenium(II)-phosphinite complexes have been used as catalysts for the asymmetric transfer hydrogenation of acetophenone derivatives. Under optimized conditions, aromatic ketones were reduced in good conversions and in moderate to good enantioselectivities (up to 85% ee).     

Chiral calix[4]arenes bearing α-hydroxy amide units as membrane carriers for amino acid methyl esters

Novel chiral calix[4]arene derivatives functionalized at the lower rim have been prepared from the reaction of p-tert-butylcalix[4]arene diamine or acylhydrazine derivative with mandelic acid or hydroxyisovaleric acid. The structures of these receptors were characterized by FTIR, ¹H, ¹³C and 2D COSY NMR spectroscopy and elemental analysis. The transport of amino acid derivatives (phenylalanine, phenylglycine and tryptophan methyl ester hydrochlorides) was studied through bulk liquid membrane in the presence of chiral calix[4]arene derivatives. The receptors have been found to act as carriers for transport of aromatic amino acid methylesters from the aqueous source phase to the aqueous receiving phase. The transport rate and L/D selectivity of amino acid esters studied depend strongly upon the structure of the chiral receptors and guests. The best enantioselectivity was obtained in the case of phenylglycine methyl ester for all chiral carriers.     

Stereoisomerism and complexation behaviour of functionalized p-tert-calix[6]-1,4-2,5-biscrown-4

p-tert-Calix[6]-1,4-2,5-biscrown-4 was subjected to functionalization by benzyl bromide or ethyl bromoacetate. Two pairs of disubstituted calix[6]biscrown stereoisomers were obtained. Their structures had been deduced from ¹H NMR and ESI-MS (electrospray ionization mass spectroscopy). One of the bisethyloxycarbonylmethylated derivatives 3a was further investigated by X-ray crystallographic analysis. Two-phase extraction experiments indicated that bisethyloxycarbonylmethylated derivatives exhibited high Cs⁺/Na⁺ selectivity. By ESI-MS and ¹H NMR experiments it was confirmed that 3a formed 1:1 complex with Cs⁺.     

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).     

An inherently chiral calix[4]crown carboxylic acid in the partial cone conformation

We have designed and synthesized an inherently chiral calix[4]arene partial cone conformer, in which a crown-4 ether moiety, a carboxyl group, and a propyl group are convergent. Chemical resolution was achieved by use of (S)-BINOL as a chiral auxiliary. ¹H NMR titration data revealed that the title compound does not have the ability to differentiate both enantiomers of chiral amine and aminoalcohol guests. The approximately symmetric calix[4]arene skeleton of the partial cone conformer is presumed to be responsible for its undesirable chiral recognition ability.     

Catalytic asymmetric chiral lithium amide-promoted epoxide rearrangement: a NMR spectroscopic and kinetic investigation

The lithium amide derived from the chiral diamine (1R,3S,4S)-3-(1-pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane, has been reported to catalytically deprotonate cyclohexene oxide and other epoxides, yielding chiral allylic alcohols in excellent enantiomeric excess. In this work, ⁶Li, ¹H and ¹³C NMR spectroscopy have been used to study the aggregation of the chiral lithium amide in THF and the influence on the aggregation by the addition of additives, such as 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The activated complex under catalytic deprotonation of cyclohexene oxide, that is, with excess Li-DBU and free DBU, is built from one monomer of the chiral lithium amide, one molecule of epoxide and one additional molecule of DBU. The reaction order (?0.97) obtained for the bulk base Li-DBU shows an inverse dependence on the concentration, suggesting a deaggregation of the initial mixed dimer to a monomer-based transition state containing a monomer of the lithium amide.     

Synthesis and in-vitro-antibacterial activity of [5-(furan-2-yl)-phenyl]-4,5-carbothioamide-pyrazolines

Cyclization of various different alkoxy [1-[2-(alkoxy)phenyl]-5-(furan-2-yl)-prop-2-en-1-one] chalcone with thiosemicarbazide in the presence of NaOH in ethanol afforded a series of novel 1-N-substituted cyclized pyrazoline analogues [5-(furan-2-yl)-3-[2-(alkoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2a–2d. The structures of these compounds were elucidated by IR, ¹H NMR, ¹³C NMR, Fab mass spectrometry and their purities were confirmed by elemental analyses. In vitro antibacterial activity of these compounds were evaluated by the disk diffusion assay and then the minimum inhibitory concentration (MIC) strain of two Gram-positive and two Gram-negative bacteria like Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus, among all the compounds, alkoxy [5-(furan-2-yl)-2-(benzyloxy)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2b and 5-(furan-2-yl)-1-[2-(naphthalen-2-ylmethoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2d showed the most promising antibacterial agent when compared to gentamicin and tetracycline.