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An electropolymerisable tetra ester calix[4]arene derivative 1 bearing four thiophene units appended at the lower rim has been synthesised. The oxidative behaviour and the ability of 1 to recognise alkaline and ammonium cations in acetonitrile solution was examined by cyclic voltammetry. The data are interpreted on the basis of the electroactivity of the four thiophene moieties as well as the electroactivity of the 2,6-disubstituted aryl ether moieties of 1. Electrochemical homopolymerisation of 1 was achieved but produced electrochemically unstable films. Electrochemical copolymerisation of 1 with 3-methylthiophene (3-MeT) was investigated. The [3-MeT]/[1] ratio was observed to influence the electrochemical stability and recognition ability for sodium cations of the resulting films.

The synthesis of a propranolol amide derivative of p-allylcalix[4]arene is described, which has been designed to behave as a molecular sensor capable of distinguishing chiral amines on the basis of their shape and chirality. This molecule can discriminate between the enantiomers of phenylalaninol through the quenching of the fluorescence emission in methanol in contrast to an (S)-dinaphthylprolinol calix[4]arene derivative, which can discriminate between the enantiomers of phenylglycinol, but not phenylalaninol. The separation between the naphthyl fluorophores and the hydrogen-bonding sites within the chiral cavity can be tuned to recognize guest amines with similar separation between aryl groups and hydrogen-bonding sites. The formation of metal ion complexes of the p-allylcalix[4]arene propranolol amide derivative is shown to induce a more regular and rigid cone conformation in the calix[4]arene macrocycle, which generates a significant enhancement in the observed enantiomeric discrimination.

The p-tert-butylcalix[4]arene tetraethylamide 2 has been synthesized and its molecular structure has been determined by X-ray diffraction, which revealed a network of intramolecular and intermolecular hydrogen bonds. Extraction experiments and complexation studies based on stability constant determinations and calorimetric measurements in methanol show that whereas this amide is inefficient in biphasic transfer from water into dichloromethane, it does complex sodium and, with the exception of magnesium, alkaline earth cations. The stability of the Na2+ complex is enthalpy controlled, while the stability of the alkaline earth complexes is entropy controlled.

Several novel thiazoles with side chains derived from natural amino acids and a dipeptide have been synthesised from N-protected α-amino glyoxals and cysteine.

A series of N-protected α-amino diazoketones has been prepared from L-amino acids and dipeptides and used as precursors in the synthesis of novel N-protected α-amino glyoxals via oxidation with distilled dimethyldioxirane (DMD) in acetone. The glyoxals have been converted, without purification, into enantiopure imines, pyrazines, quinoxalines, and pyrido[2,3-b]pyrazines via condensation with the appropriate amine or diamine. The molecular structure of the pyrido[2,3-b]pyrazine derived from N-Cbz-L-phenylalanine has been determined by X-ray analysis.

We have discovered that a series of calixarene phosphine oxide derivatives can produce ion-selective electrodes with excellent response characteristics to the Pb2+ ion. These ligands were previously known to complex lanthanides, but their complexation behavior with transition metal ions and group I/group II ions is relatively unexplored. The extreme stability of these compounds, coupled with interesting selectivity behavior, make them attractive contenders for use in potentiometric poly(vinyl chloride) membrane electrodes. Results show near-Nernstian responses to Pb2+ for electrodes based on three ligands (p-tert-butylcalix[n]arene ethyleneoxydiphenylphosphine oxide, n = 4, 5, 6) and excellent selectivity against a wide range of common interferences. Ca2+ was found to be the most important interference, but its impact dramatically decreased as the cavity size increased from the tetramer (n = 4) through the pentamer (n = 5) to the hexamer (n = 6). Electrodes based on the hexamer were found to have characte...

N-Z-γ-amino alcohols derived from nonracemic β-amino acids are smoothly oxidised by manganese dioxide in acetonitrile to afford aldehydes which can be trapped in situ in Wittig reactions with carbonyl-substituted phosphoranes. The application of this methodology to the synthesis of the alkaloids (S)-(+)-N-BOC-coniie, (S)-(−)-coniceine and a pipecoline precursor is described.

Three rhenium(V) oxo phosphine complexes and methyltrioxorhenium have been used as catalysts for oxidation of sulfides to sulfoxides with urea-hydrogen peroxide as oxidant in acetonitrile; partial enantioselective oxidation of methylphenyl sulfide was observed with methyltrioxorhenium in the presence of a (+)-camphor derived pyrazine carboxylic acid.

Methyltrioxorhenium is an efficient catalyst for the oxidative ring opening of several substituted furans to enediones using urea hydrogen peroxide

The conformation of a p-tert-butylcalix[4]arene with four (R)-1(1-phenyl-ethyl)carbamic acid ethoxyester residues on the lower rim has been investigated by X-ray diffraction and 1H NMR analysis. The molecule adopts a pinched cone conformation in the solid state with intramolecular hydrogen bonding between the carbonyl groups and the nitrogen atoms of proximal carbamate podands. The NMR evidence indicates that this conformation persists in solution at room temperature. At temperatures >80°C the NMR spectrum is that of a time-averaged C4v symmetrical cone conformation.

A lipase-catalysed transesterification to effect a desymmetrisation has been used to produce chiral calix[4]arene derivatives with enantiomer excesses (ee) of up to 100%.

A series of peptidyl α-keto aldehydes (glyoxals) have been synthesised as putative inhibitors of the chymotryptic-like activity of proteasome. The most potent peptides, Cbz-Leu-Leu-Tyr-COCHO and Bz-Leu-Leu-Leu-COCHO, function as slow-binding reversible inhibitors, exhibiting final K i values of approximately 3.0 nM. These are among the lowest values so far reported for (tri)peptide-based aldehyde-releated inhibitors.

Molecular mechanics calculations have been used to model the geometries of the complexes of Group I metal ions with calix[n]arenes (n = 4,5). A simple procedure in which the calixarene atoms are assigned partial charges on the basis of AM1 calculations and the metal ions are allowed to bind electrostatically to the calixarenes produces surprising good results when the resulting structures are compared to known crystallographic data on the complexes. Encapsulated solvent molecules and/or counterions can be included in the calculations and, indeed, are necessary to reproduce the X-ray data.

Several new chiral rhodium(II) catalysts have been synthesised for evaluation as catalysts in asymmetric oxonium ylide-[2,3] sigmatropic rearrangement of diazocarbonyl substrates; a catalyst derived from (S)-tert-leucine afforded a chiral benzofuranone derivative with an ee of 60 %.

Two calix[4]arene derivatives, in the partial cone conformation, with sulfur-containing functionalities, were tested as neutral carrier ionophores in potentiometric silver-selective electrodes of conventional membrane and membrane-coated glassy carbon electrode types. Comparison with a calix[4]arene in the cone conformation was made. The membranes were prepared using either 2-nitrophenyl octyl ether or bis(ethylhexyl)sebacate as plasticizers and potassium tetrakis(p-chlorophenyl)borate as the lipophilic salt in a poly(vinyl chloride) matrix. Both calix[4]arenes yielded electrodes of good sensitivity (approx. 47 mV dec−1) in the range 10−4–10−1 M and excellent selectivity [log KAg,MH+ < −1.5] of transition, alkali and heavy metal cations, including sodium, mercury(II) and lead(II) cations. Temperature effects and reproducibility of response were determined and the interfering effects of mercury(II) and lead (II) ions on the membranes were noted. The partial cone conformation allows improved selectivity over certain cations relative to calix[4]arenes in the cone conformation.

The effect of chemical modification of the lower rim of p-tert-butylcalix[4]-, [5]- and [6]-arenes has been analysed with respect to cation binding by thioamide podands. Extraction data for metal picrates from water into dichloromethane are discussed. CuII, PbII and AgI ions are extracted efficiently by all the thioamides studied, whereas extraction of CdII only reaches significant levels with the pentamer derivative. Unlike their calixarene amide counterparts, these thioamides have no affinity in extraction for either alkali or alkaline earth metals. The X-ray molecular structure of a thioamide–PbII(ClO4)2 complex and, for comparison, that of an amide–CuII(ClO4)2 complex have been determined. Both complexes exist in the cone conformation with the metal ion encapsulated by the heteroatoms on the lower rin. The crystal structure of the lead complex derivative 5·Pb(ClO4)2·EtOH·0.5 H2O, was solved by Patterson methods and refined by block diagonal least-squares analysis. The crystals are triclinic, space group P, a = 13.394(6), b = 13.459(6), c = 26.711(4) A, a = 78.33(2), β = 87.62(2), γ = 60.46(2)° with R = 0.108 for 4417 observed reflections. The Pb2+ is bonded to the four ethereal oxygen and four thiocarbonyl sulfur atoms, [Pb–O, 2.65(2) to 2.72(2), mean value 2.68(3) A; Pb–S, 2.82(1) to 2.95(1) with a mean of 2.91(3) A]. The crystal structure of the copper calixarene complex 2·Cu(ClO4)2·H2O ·1.4CH3OH·EtOH, was solved by direct methods and refined by block-diagonal least-squares methods. The crystals are tetragonal, space group P4/ncc a = 17.147(2), c = 28.054(4) A, with R = 0.079 for 1482 observed reflections. The Cu2+ resides on a four-fold axis and is bonded to the four carbonyl oxygen atoms [Cu–O, 1.926(6) A]. Four ethereal oxygen atoms are at a distance of 2.963(6) A from the metal ion.

The binding abilities of a series of ionizable calixarenes towards three lanthanides (Pr 3+ , Eu 3+ and Yb 3+ ) and one actinide (Th 4+ ) have been established in methanol by potentiometric measurements. The calixarenes result from progressive substitution of the phenolic hydrogens of p-tert-butylcalix[4]arene by carboxylic acid functions. Calixarene derivatives with mixed carboxylic and ester functional groups, as well as octa-O-carboxymethyl-p-tert-butylcalix[8]arene and the two oxa-derivatives, tetra-O-carboxymethyl-p-tert- butyltetrahomodioxacalix[4]arene and tri-O-carboxymethyl-p-tert- butylhexahomotrioxacalix[3]arene have also been studied. The formation of 1 : 1 species partially protonated [M(H z L)] and totally deprotonated (ML) as well as methoxo species [{ML(OMe) z }] has been established with lanthanides. Additional binuclear complexes and their methoxo forms have been found in some cases. With thorium the mononuclear ML and MHL complexes are mainly formed in addition to the corresponding methoxo species at high pH. For a given ligand, the stability of the complexes increases with the cationic charge: complexes of thorium are more stable than those of lanthanides, which are themselves generally more stable than the corresponding alkaline-earth- and alkali-metal complexes. The predominance of electrostatic interactions in the binding is further confirmed by a linear relationship between the stability of mononuclear complexes (log β 110 ) and the total basicity of the ligands (ΣpK ai ). The p-tert-butylcalix[8]arene octaacid and the p-tert-butylcalix[4]arene monoacid are respectively the best complexing agents for the lanthanides and thorium. The monoacid derivative shows significant Yb 3+ /Eu 3+ and Th 4+ /Eu 3+ selectivities in appropriate pH ranges.

The detection of gaseous ammonia using an optical evanescent wave sensor coated with a PVC film containing a chromogenic calixarene (nitrophenylazophenol calix[4]arene) is described. On addition of various concentrations of ammonia gas, the absorbance maximum shifts to 500 nm, which is characteristic of deprotonation of the chromogenic group. The sensitivity of the sensor to ammonia varied depending on whether the free ligand or lithium complex was used in the membrane. Intermediate sensitivities can be generated by varying the mole ratio of lithium to calixarene. The response time of the lithium complex measured at 520 nm to a 5–50 ppm change in ammonia concentration is fast (several minutes to steady state) but the signal is slow to return to the baseline when the gas is replaced by nitrogen.

The performance of sodium selective electrodes based on the triethylacetate and trimethylacetate monoacid derivatives of p-tert-butylcalix[4]arene is described together with their tetraester analogues. All electrodes showed slopes in excess of 50 mV dec−1 (53.5–56 mV dec−1) and lifetimes of at least 35 days. Virtually no difference in selectivity between the monoacid derivatives and the tetraesters was found. pH stability studies showed that the monoacid derivatives gave best performance at neutral pH but at alkaline pH (>8) there was a reduction in response which did not occur with the tetraesters. This difference in behaviour may be due to deprotonation of the monoacid derivatives at high pH values at the aquo-membrane boundary prior to complexation.

X-Ray crystallographic analyses of four p-tert-butylcalix[4]arenes in which two 1,3-(distal)phenolic groups on the lower rim have been derivatised with cyanomethyl, amino ester and alkyl acetate residues, are reported. Intramolecular hydrogen bonding between the free phenolic groups and their proximal ethereal oxygen atoms is evident in all four compounds. With the exception of the ethyl ester, these calixarenes adopt very distorted cone conformations in the solid state. The ethyl ester adopts a much less distorted cone conformation with the distinguishing feature of self-inclusion of an ethoxy residue of one ester group on the lower rim within the hydrophobic cavity of a neighbouring molecule within the crystal. Factors which control the conformations of these molecules are discussed.

p-tert-Butylcalix[4]arene derivatives 2 and 4 bearing one carboxy-lic acid, one ester and two phenolic groups on the lower rim form pH-dependent mononuclear or binuclear assemblies with alkali (excluding lithium) and alkaline earth cations. The structures of binuclear K+ complexes 5 and 6 of 2 and 4, respectively, have been determined by X-ray diffraction.

The highest levels of enantiocontrol in intermolecular cyclopropanation reactions of methyl phenyldiazoacetate have been achieved with homochiral dirhodium(II) prolinates in pentane, the solvent effect for which (0.8 ± 0.2 kcal/mol) is associated with ligand alignment.

Formylphosphonate hydrate has been synthesised by the oxidation of diazomethylphosphonate with dimethyldioxirane (DMD) and its reactions, including the formation of imines, oximes, and Wittig olefination products, have been investigated. Formylphosphonate also acts as an efficient, selective formylating agent of secondary amines. β-Ketophosphonic acids derived from a range of amino acids have been prepared by the tin (II) chloride-catalysed reaction of diazomethylphosphonate with amino aldehydes and in certain cases shown to be potent inhibitors of leucine aminopeptidase.

The fluorinated furanose unit of the anti-HIV-active nucleoside (2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine, β-FddA, has been synthesized as its 5-trityl derivative with high stereocontrol from ( S )-trityl glycidol and phenylthioacetic acid.

Good levels of enantioselectivity have been achieved in intramolecular C–H insertion reactions of α-diazocarbonyl compounds leading to six-membered oxygen heterocycles (chromanones) through the use of chiral rhodium(II) carboxylates as catalysts. Competition between C–H insertion and sigmatropic rearrangement, the latter leading to five-membered oxygen heterocycles (furanones), was observed with precursors containing a proximal O-allyl side chain. Whereas rhodium carboxylates produced C-H insertion products predominantly, a copper catalyst produced sigmatropic rearrangement products exclusively. A precursor with an S-allyl side chain exhibited cyclisation via sigmatropic rearrangement with both copper and rhodium catalysts.

Rhodium(II) catalysed decomposition of γ-alkoxy-α-diazo-β-ketoesters produce cis-2,5-disubstituted -3(2H)-furanones with high ( > 97%) stereoselectivity. The combination of a chiral auxiliary in the ester moiety of the diazo precursor and a chiral catalyst can lead to asymmetric synthesis with diastereoselectivities up to 61% de.

The complexing ability of a range of 19 symmetrical, unsymmetrical and bridged calix[4]arene derivatives having ester, ketone, amide, amine and thioether functionalities were determined by the picrate extraction method. On incorporating these calix[4]arene derivatives as neutral carrier ionophores in sodium-selective poly (vinyl chloride) membrane electrodes the performance was assessed on the basis of the sensitivity and selectivity over the alkali, alkaline earth metals and hydrogen and ammonium ions. The temperature dependence, response times and lifetimes were also determined. Four ionophores in particular gave excellent sensitivity and selectivity and lifetimes of > 200 days. These electrodes were then tested without additional lipophilic additives and one ionophore was incorporated into poly (vinyl chloride) membrane electrodes with plasticizing solvents of varying polarity.

The synthetic macrocycles, known as calixarenes, have been shown to possess high ionophoric selectivity and form inclusion complexes with many ions. A tetrameric calixarene bearing hydroxamic acid functional groups was synthesised and supported on octadecylsilica and XAD-4 resin. When loaded with Fe(III), V(V) and Cu(II), the materials display the characteristic visible absorption spectra associated with hydroxamate coordination. The chemical bonding of the calixarene tetrahydroxamic acid to silica particles was also carried out using the triethoxysilane derivative of the p -allylcalix[4]arene hydroxamic acid. When packed into small cartridges, these materials are used for the solid phase extraction of transition metal ions from aqueous solution. Metal uptake profiles as a function of pH are presented for Fe(III), Co(II), Pb(II), Cd(II), Mn(II), Ni(II), Zn(II) and Cu(II). The quantitative trace enrichment of Cu(II), Zn(II) and Mn(II) from water samples prior to ion chromatographic analysis is demonstrated

The use of calixarene-based chemically modified carbon paste electrodes (CMCPEs) in voltammetric analysis is reported here. A polymeric calixarene I was incorporated successfully and used for the accumulation of lead (II), copper(II), and mercury(II) ions with subsequent anodic stripping voltammetry as the determination step. The electrode response depended on the calixarene content, the electrolyte, and the preconcentration time and analyte concentration as well as the constituents of the sample matrix. The presence of alkali metal ions in the sample solution was found to have an adverse effect on electrode response, due to the preferable binding of these ions by the calixarene units immobilized in the carbon paste. Attempts to overcome this interference employed a nonpolymeric sulfur-containing calixarene, the thioamide II, in the electrode. The stripping current was not enhanced by introduction of this compound as an electrode modifier, perhaps due to adsorption of the calixarene on the carbon partnicles via its metal ion binding site. However, the application of calixarenes to voltammetric methods of analysis is demonstrated and provides an additional use of calixarenes in electroanalysis.

The complexing properties of some calix[4]arenes in which carboxylic acid ligating groups have been progressively attached to the lower rim through the phenolic hydrogen atoms have been measured with alkali and alkaline-earth metal cations in methano by means of potentiometric titrations. The acid-base characteristics of these compounds were first determined. the weak acidities generally observed may be explained by the formation of intramolecular hydrogen bonding.

Functional esters of calixarenes, which are phenolic metacyclophanes annulated by a single methylene bridge, are immobilised onto silica particles for use in the separation of alkali metal ions by high performance liquid chromatography with conductivity detection. The immobilisation of tetrameric and hexameric calixarene ethyl esters was carried out using the triethoxy silane derivatives of p-allylcalix[n]arene ethyl esters. At an injected concentration of 10−2M, optimum selectivity for Na ions was achieved using a mobile phase of 30% MeOH/H2O with the calix[4]arene ester stationary phase. A mixture of four alkali metal chlorides is shown on injection to give a clear separation of Na+ from the other unresolved ions, the retention order being Na+ » K+ > Cs+ > Li+ = to.

Reaction of a 1,3-diacid dichloride 1d of p-tert-butylcalix[4]arene with various aliphatic diamines including diaza-15-crown-5 and diaza-18-crown-6 yields calixarenes capped by diamide bridges, in yields of 19–95%. The tendency for capping is so pronounced with ethylenediamine that cyclic diamide 2a is formed even in the presence of an excess of diamine. Crystals of the ethylenediamine adduct 2a and of the N,N′-dimethylethylenediamine adduct 2c were studied by X-lay diffraction. Crystals of adduct 2a are monoclinic, space group C2/c, a= 36.140(4), b= 11.879(3), c= 25.801(6)A, β= 114.66(2)° with R= 0.077 for 3044 observed reflections. Crystals of adduct 2c are triclinic, space group P1, a= 10.272(2), b= 12.474(3), c= 19.351 (4)A, α= 93.799(18), β= 95.524(l 5), γ= 91.584(18)° with R= 0.076 for 2317 observed reflections. While adduct 2a includes a molecule of dichioromethane in its hydrophobic cavity, the distortion of the cone conformation in adduct 2c is too severe to allow the inclusion of a guest. This distorted chiral conformation of adduct 2c(C2 symmetry) is also stable in solution at room temperature.

N-Z-γ-amino alcohols derived from nonracemic β-amino acids are smoothly oxidised by manganese dioxide in acetonitrile to afford aldehydes which can be trapped in situ in Wittig reactions with carbonyl-substituted phosphoranes. The application of this methodology to the synthesis of the alkaloids (S)-(+)-N-BOC-coniie, (S)-(−)-coniceine and a pipecoline precursor is described.

The reductive amination of an amino acid derived glyoxal, with the free amino group of a protected amino acid or oligopeptide fragment, has been developed as a simple and efficient method for the preparation of ketomethylene amino pseudo-oligopeptide isosteres AaΨ(COCH 2 NH)Aa. Trichlorosilane–DMF is the reagent of choice for the reduction.

Several novel thiazoles with side chains derived from natural amino acids and a dipeptide have been synthesised from N-protected α-amino glyoxals and cysteine.

Four lipophilic sulphur and/or nitrogen containing calixarene derivatives have been tested as ionophores in Ag(I)-selective poly (vinyl chloride) membrane electrodes. All gave acceptable linear responses with one giving a response of 50 mV/dec in the Ag(I) ion activity range 10(-4)-10(-1)M and high selectivity towards other transition metals and sodium and potassium ions. This ionophore was also tested as a membrane coated glassy-carbon electrode where the sensitivity and selectivity of the conventional membrane electrode was found to be repeated. The latter electrode was then used in potentiometric titrations of halide ions with silver nitrate.

A new homochiral Rh(II) complex, Rh{HCO3}2{(+)-phos}2·5H2O, where (+)phosH represents (S)-(+)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate, has been prepared and used as a catalyst for reactions of diazocarbonyl compounds leading to enantioselective 2,3-sigmatropic rearrangement (first example), C H insertion and aromatic cycloaddition

A series of bridged calix [4] arenes (5–10 methylene groups in the bridge) were synthesized and transformed into their tetraester derivatives by reaction with ethyl bromoacetate. The stability constants for complexes of the tetraester derivatives with sodium, potassium and silver cations, determined in methanol by spectroscopic or potentiometric techniques, show a drastic decrease (more than 105 for Na +) for the shorter methylene chains. 1H NMR studies demonstrate a conformational rearrangement of the calixarene part to fourfold symmetry to be necessary for the complexation of a cation, which is prevented by the shorter chains. This is further confirmed by the X-ray structure of a tetraester derivative with a CH2CH2COCH2CH2 bridge; crystals were monoclinic, space group P21/c,a = 11.847(2), b = 39.773(5), c = 12 · 127(2) A, β = 109.24(1), V = 5395.1 A3, Z = 4, Dx = 1.186 Mg m−3.

Homochiral Rh(II) carboxylates, Rh2(OCOR)4, are readily prepared in good yield by reaction of carboxylic acids with the Rh(II) carbonato species, Na4Rh2(CO3)4.

α-Diazoketols, prepared by condensation of aldehydes or ketones with lithiated optically active α-diazoketones derived from natural amino acids, rearrange to homochiral α-amino-β-diketones on treatment with rhodium(II) acetate.

1 Introduction 2 Cyclopropanation Using Diazoalkanes 3 Cyclopropanation Using Diazocarbonyl Compounds 4 Cyclopropanation Using Other Precursors 5 Chemoselectivity in Metal Catalysed Cyclopropanation 6 Regioselectivity in Metal Catalysed Cyclopropanation 7 Stereochemical Features of Alkene Cyclopropanation 8 Conclusion Keywords: metal catalysed cyclopropanation; cyclopropanation using diazoalkanes; cyclopropanation using diazocarbonyl compounds; regioselectivity in metal catalysed cyclopropanation; stereochemical features of alkene cyclopropanation; enantioselectivity in metal catalysed cyclopropanation

The development of an ion-sensitive field-effect transistor for sodium ions is described. Cahx[4]arene derivatives incorporated in a poly(vinyl chloride)-based membrane provide the selectivity. A poly(2-hydroxyethyl methacrylate) interlayer between the silicon dioxide gate and the sensing membrane is necessary to obtain a Na+-sensitive ISFET with Nernstian behaviour. The potentiometric selectivity coefficients (log Kij pot) for Na+ over K+ and Li+ are ¿1.9 and ¿2.5