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Diastereoisomers

Distribution by Scientific Domains
Chemistry90%
Life Sciences9%
Distribution within Chemistry
Organic Chemistry32%
General & Introductory Chemistry20%
Crystallography15%
7 Other Subdomains33%

Selected Abstracts

Dietary accumulation of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss) I: Bioaccumulation parameters and evidence of bioisomerization

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2006
Kerri Law
Abstract Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to three diastereoisomers (,, ,, ,) of hexabromocyclododecane (C12H18Br6) via their diet for 56 d followed by 112 d of untreated food to examine bioaccumulation parameters and test the hypothesis of in vivo bioisomerization. Four groups of 70 fish were used in the study. Three groups were exposed to food fortified with known concentrations of an individual diastereoisomer, while a fourth group were fed unfortified food. Bioaccumulation of the ,-diastereoisomer was linear during the uptake phase, while the ,- and ,-diastereoisomers were found to increase exponentially with respective doubling times of 8.2 and 17.1 d. Both the ,- and the ,-diastereoisomers followed a first-order depuration kinetics with calculated half-lives of 157 ± 71 and 144 ± 60 d (±1 × standard error), respectively. The biomagnification factor (BMF) for the ,-diastereoisomer (BMF = 9.2) was two times greater than the ,-diastereoisomer (BMF = 4.3); the large BMF for the ,-diastereoisomer is consistent with this diastereoisomer dominating higher-trophic-level organisms. Although the BMF of the ,-diastereoisomer suggests that it will biomagnify, it is rarely detected in environmental samples because it is present in small quantities in commercial mixtures. Results from these studies also provide evidence of bioisomerization of the ,- and ,-diastereoisomers. Most importantly, the ,-diastereoisomer that was recalcitrant to bioisomerization by juvenile rainbow trout in this study and known to be the dominant diastereosiomer in fish was bioformed from both the ,- and the ,-diastereoisomers. To our knowledge, this is the first report of bioisomerization of a halogenated organic pollutant in biota. [source]

1-Alkoxyamino-2-nitroalkanes as Key Building Blocks for a Chemo- and Diastereoselective Synthesis of a New Type of Polyfunctionalized N -Alkoxypiperidine

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2010
M. Ángeles López-García
Abstract A highly efficient conversion of ,-nitrostyrenes into a new kind of functionalized N -alkoxy-2-hydroxypiperidine in two steps was developed, giving excellent yields and diastereoselectivity. The prepared compounds are the first examples of N -alkoxy-2-hydroxypiperidines. The synthetic approach involved the conjugate addition of alkoxyamines to ,-nitrostyrenes, followed by Michael addition of the isolated nitroalkoxyamines to ,,,-unsaturated carbonyl compounds, and intramolecular addition of the alkoxyamino group to the carbonyl functionality of the (non-isolated) adducts. Although three stereogenic centers are formed, only one diastereoisomer was detected. This unprecedented sequence of reactions can also be performed in a one-pot fashion. [source]

Ex-Chiral-Pool Synthesis of ,-Hydroxyphosphonate Nucleoside Analogues

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2007
Franck Gallier
Abstract A new series of mononucleotide analogues bearing a nonhydrolysable P,C bond instead of the P,O phosphate linkage is presented. We intend to set up an approach that allows the synthesis of ,-hydroxyphosphonate nucleoside analogues as a single diastereoisomer. In this respect, the key "sugar-phosphonate" intermediate was obtained through an Arbusov reaction from an iodosugar derivative in which the stereochemistry of the ,-hydroxy group is determined by the choice of the starting material and remains in the resulting nucleotide analogues. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

An Efficient Synthesis of 2-Bromo-3-hydroxy Esters by Reaction of Ketones with Ethyl Dibromoacetate Promoted by Samarium Diiodide

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2006
José M. Concellón
Abstract A simple and efficient samarium diiodide mediated synthesis of 2-bromo-3-hydroxy esters 1 by the reaction of a variety of ketones 2 with ethyl dibromoacetate (3) is described. The relative configuration of the major diastereoisomer obtained was established by NOESY experiments of the corresponding ,,,-epoxy esters 4 prepared from 1. Additionally, a mechanism is proposed to explain the results obtained. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]

Stereoelectronic Effects in the Iodine-Promoted Oxidation of Pentacyclic Tetrahydroisoquinolines

HELVETICA CHIMICA ACTA, Issue 8 2004
Oliver Koepler
Iodine-promoted oxidations of the pentacyclic tetrahydroisoquinolines 4a, 4b, and 10 were investigated. Whereas the all- cis diastereoisomer 4a containing an arylamino moiety gave the iminium ion 5 as the primary product, which subsequently underwent intramolecular aminal formation to 6, the corresponding all- trans diastereoisomer 4b epimerized to the all- cis diastereoisomer 4avia iminium ion 7. In contrast, tetrahydroisoquinoline 10 could be cleanly oxidized to the corresponding isoquinolizidinium ion 11. Mechanistic considerations were supported by molecular-modeling calculations. [source]

Axially Chiral Phosphine-Oxazoline Ligands in Silver(I)- Catalyzed Asymmetric Mannich Reaction of Aldimines with Trimethylsiloxyfuran

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2009
Hong-Ping Deng
Abstract A new asymmetric catalytic system for the Mannich reaction of aldimines with trimethylsiloxyfuran is described. The combination of an axially chiral phosphine-oxazoline ligand (S)-2-[(R)-2,-(diphenylphosphino)-1,1,-binaphthyl-2-yl]-4-phenyl-4,5-dihydrooxazole with silver acetate and 2,2,2-trifluoroacetic acid is a very effective catalytic system in the asymmetric Mannich reaction of various aldimines with trimethylsiloxyfuran in dichloromethane at ,78,°C, affording the corresponding adducts in up to 99% yield, 99:1 (dr) and 99% ee (major diastereoisomer) under mild conditions. [source]

Stereoselective Synthesis of Metalated Cyclobutyl Derivatives

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2009
Einav Tsoglin
Abstract Treatment of Z -vinyl carbamates with dicyclopentadienyl(diethyl)zirconium [Et2ZrCp2] leads to cyclobutyl-zirconocene derivatives in good yields and as a unique diastereoisomer. The reaction proceeds through a carbometalative ring-expansion followed by an intramolecular migratory insertion. [source]

Effect of solvent on the inversion of pyramidal sulfonium and selenonium compounds

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2001
Andreas Wiegrefe
Abstract The effects of temperature and solvent on the cis,trans equilibrium and isomerization rates of different cyclic sulfonium and selenonium compounds were investigated by 1H NMR spectroscopy. A non-dissociative process was considered to be the most probable mechanism for inversion of configuration. While the temperature had no apparent effect on the equilibrium, in which the trans -diastereoisomer dominated in all cases, changing the solvent from dimethylformamide to acetonitrile and to water led to increasing amounts of the cis -diastereoisomer. Additionally, the rate of stereomutation of the thiolanium compound was slowed by a factor of 2 and that of the selenolanium compound by a factor of 85. While the pyramidal (vertex) inversion is the most probable mechanism for the sulfonium compounds investigated, some evidence is presented that indicates that the selenonium compound could isomerize via an edge inversion mechanism. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Ln3M1,,,,TX7, quasi-isostructural compounds: stereochemistry and silver-ion motion in the Ln3Ag1,,,,GeS7 (Ln = La,Nd, Sm, Gd,Er and Y; , = 0.11,0.50) compounds

ACTA CRYSTALLOGRAPHICA SECTION B, Issue 2 2009
Marek Daszkiewicz
The crystal structures of the Ln3Ag1,,,,GeS7 (Ln = La,Nd, Sm, Gd,Er, Y; , = 0.11,0.50, space group P63) compounds were determined by means of X-ray single-crystal diffraction and the similarities among the crystal structures of all Ln3M1,,,,TX7 (space group P63; Ln , lanthanide element, M, monovalent element; T, tetravalent element and X, S, Se) compounds deposited in the Inorganic Crystal Structure Database (ICSD) are discussed. Substitutions of each element in Ln3M1,,,,TX7 result in a different structural effect. On the basis of the data deposited in the ICSD the large family of the Ln3M1,,,,TX7 compounds was divided into three groups depending on the position of the monovalent element in the lattice. This position determines what kind of stereoisomer is present in the structure, either the ++ enantiomer or the +, diastereoisomer. Since the silver ions can occupy a different position and the energy barriers between positions are low the ions can move through the channel. It was shown that this movement is not a stochastic process but a correlated one. [source]

A three-dimensional hydrogen-bonded framework in (2S*,4R*)-7-fluoro-2- exo -[(E)-styryl]-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 4 2010
Lina M. Acosta
Molecules of the title compound, C18H16FNO, are linked into a three-dimensional framework structure by a combination of two C,H...O hydrogen bonds and three C,H...,(arene) hydrogen bonds. Comparisons are made with the (2R,4R) diastereoisomer and with the corresponding pair of diastereoisomeric 7-chloro analogues. [source]

Hydrogen-bonded dimers, chains and rings in six differently substituted 2-vinyltetrahydro-1,4-epoxy-1-benzazepines

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 4 2010
Lina M. Acosta
In (2SR,4RS)-2- exo -vinyl-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C12H13NO, (I), the molecules are linked by two independent C,H...,(arene) hydrogen bonds to form sheets, such that all of the molecules in a given sheet are of the same configuration. The molecules of (2SR,4RS)-7-chloro-2- exo -(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C14H16ClNO, (II), are linked by a C,H...O hydrogen bond into C(4) chains, where all the molecules in a given chain are of the same configuration, whereas the molecules of (2SR,4RS)-8-chloro-9-methyl-2- exo -(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C15H18ClNO, (III), are linked into centrosymmetric dimers by pairs of symmetry-related C,H...,(arene) hydrogen bonds. (2RS,4RS)-8-Chloro-9-methyl-2- endo -(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C15H18ClNO, (IV), is a diastereoisomer of (III) and, as for (II), a single C,H...O hydrogen bond links the molecules into C(4) chains, each containing molecules of a single configuration. The structure of (2SR,4RS)-8-chloro-9-methyl-2- exo -(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C14H16ClNO, (V), contains a C,H...O hydrogen bond which links pairs of molecules into centrosymmetric R22(6) dimers. (2SR,4RS)-7,9-Dichloro-2- exo -(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H -1,4-epoxy-1-benzazepine, C13H13Cl2NO, (VI), is an inversion twin containing both the (2S,4R) and (2R,4S) enantiomers in the space group P21, and a C,H...O hydrogen bond links molecules of a given configuration into simple C(3) chains. [source]

Aldol Additions of Dihydroxyacetone Phosphate to N -Cbz-Amino Aldehydes Catalyzed by L -Fuculose-1-Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor Aldehyde

CHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2005
Laia Espelt Dr.
Abstract The potential of L -fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N -protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100,mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N -protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)- N -Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N -Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N -Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N -Cbz-glycinal and N -Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after CC bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results. [source]

Diastereoisomeric assignment in a pacifenol derivative using vibrational circular dichroism,

CHIRALITY, Issue 1E 2009
Marcelo A. Muńoz
Abstract The configuration of a chiral center in semisynthetic (,)-(2R,5R,5aR,8,,9aS)- 2,8-dibromo-2,5,9,9a-tetrahydro-5-hydroxy-5,8,10,10-tetramethyl-6H -2,5a-methano-1-benzoxepin-7(8H)-one (3 or 4), prepared in two steps from (,)-(2R,5R,5aR,7S,8S,9aS)-2, 7-dibromo-8-chloro-2,5,7,8,9,9a-hexahydro-5,8,10,10-tetramethyl-6H -2,5a-methano-1-benzoxepin-5-ol, known as pacifenol 1, has been determined using vibrational circular dichroism (VCD) measurements. The vibrational spectra (IR and VCD) of diastereoisomers 3 and 4 were calculated using density functional theory (DFT) at the B3LYP/DGDZVP level of theory for the two conformers that in each case account for the total energetic distribution found in the first 10 kcal/mol range. The DFT conformational optimization of the 8R diastereoisomer 3 indicates the cyclohexanone exists almost exclusively in a boat conformation with a ,-equatorial bromine atom and an ,-axial methyl group at the chiral center alpha to the carbonyl group, while for the 8S diastereoisomer 4 a 5:1 conformational distribution in favor of a chair conformation with an ,-axial bromine atom and a ,-equatorial methyl group is calculated, suggesting due to well-known chair versus boat relative stabilities that the plausible diastereoisomer would be the 8S molecule. A comparison of the IR spectrum of the reaction product with the calculated spectra of 3 and 4 provided no means for the diastereoisomeric assignment, while from comparison of the VCD spectra it became immediately evident that the rearranged molecule possesses the 8R absolute configuration as shown in 3, in concordance with a single crystal X-ray diffraction study that could be refined to an R -factor of 2.9%. Chirality 21:E208,E214, 2009. © 2009 Wiley-Liss, Inc. [source]

Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresis

ELECTROPHORESIS, Issue 10 2005
Andrea Baldacci
Abstract A capillary electrophoresis (CE) method for the separation of the diastereoisomers of 6-oxycodol (6OCOL) and nor-6-oxycodol (N6OCOL), the 6-keto-reduced metabolites of oxycodone (OCOD) and noroxycodone (NOCOD), respectively, is reported and employed to assess the stereoselectivity of these metabolic steps in vivo, in vitro, and in chemical synthesis. CE in an untreated fused-silica capillary with acidic buffers containing 2-hydroxypropyl-,-cyclodextrin, randomly sulfated ,-cyclodextrin, or single isomer heptakis(2,3-diacetyl-6-sulfato)-,-cyclodextrin (HDAS-,-CD) is shown to permit the simultaneous separation of the stereoisomers of 6OCOL and N6OCOL. A 100 mM phosphate buffer of pH 2.0 containing 2.05% w/v HDAS-,-CD provides a medium for rapid analysis and unambiguous identification of these stereoisomers in solid-phase extracts of (i) urines stemming from patients under pharmacotherapy with OCOD, (ii) incubations of OCOD and NOCOD with human liver cytosol and the human liver S9 fraction, and (iii) after chemical synthesis from OCOD and NOCOD using NaBH4. In all cases, ,-N6OCOL is shown to be the predominant stereoisomer of N6OCOL. For 6OCOL, the same is true for in vitro formation and for chemical synthesis. In urine, however, ,-6OCOL is observed to be excreted in a higher amount than ,-6OCOL. For the urinary ,-/,-isomer ratio of 6OCOL and N6OCOL, there are no differences between the data obtained for nonhydrolyzed and enzymatically hydrolyzed urines. The data document the stereoselectivity of the 6-keto-reduction of OCOD and NOCOD in man. [source]

Dietary accumulation of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss) I: Bioaccumulation parameters and evidence of bioisomerization

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2006
Kerri Law
Abstract Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to three diastereoisomers (,, ,, ,) of hexabromocyclododecane (C12H18Br6) via their diet for 56 d followed by 112 d of untreated food to examine bioaccumulation parameters and test the hypothesis of in vivo bioisomerization. Four groups of 70 fish were used in the study. Three groups were exposed to food fortified with known concentrations of an individual diastereoisomer, while a fourth group were fed unfortified food. Bioaccumulation of the ,-diastereoisomer was linear during the uptake phase, while the ,- and ,-diastereoisomers were found to increase exponentially with respective doubling times of 8.2 and 17.1 d. Both the ,- and the ,-diastereoisomers followed a first-order depuration kinetics with calculated half-lives of 157 ± 71 and 144 ± 60 d (±1 × standard error), respectively. The biomagnification factor (BMF) for the ,-diastereoisomer (BMF = 9.2) was two times greater than the ,-diastereoisomer (BMF = 4.3); the large BMF for the ,-diastereoisomer is consistent with this diastereoisomer dominating higher-trophic-level organisms. Although the BMF of the ,-diastereoisomer suggests that it will biomagnify, it is rarely detected in environmental samples because it is present in small quantities in commercial mixtures. Results from these studies also provide evidence of bioisomerization of the ,- and ,-diastereoisomers. Most importantly, the ,-diastereoisomer that was recalcitrant to bioisomerization by juvenile rainbow trout in this study and known to be the dominant diastereosiomer in fish was bioformed from both the ,- and the ,-diastereoisomers. To our knowledge, this is the first report of bioisomerization of a halogenated organic pollutant in biota. [source]

Structural, Spectroscopic, and Proton-Coupled Electron-transfer Behavior of Pyrazolyl-3,5-bis(benzimidazole)-Bridged Homo- and Heterochiral RuIIRuII, OsIIOsII, and OsIIRuII 2,2,-Bipyridine Complexes

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 4 2010
Sujoy Baitalik
Abstract The homo- and heterobimetallic complexes [(bpy)2MII(H2pzbzim)M,II(bpy)2](ClO4)3·nH2O (1, 3, 5) and their corresponding deprotonated complexes [(bpy)2MII(pzbzim)M,II(bpy)2](ClO4)·nH2O (2, 4, 6) [where MII, M,II = Ru (1, 2) = Os (3, 4); MII = Os and M,II = Ru (3, 5); bpy = 2,2,-bipyridine; H3pzbzim = pyrazole-3,5-bis(benzimidazole)] were synthesized, separated to their heterochiral (a, ,,/,,) and homochiral (b, ,,/,,) diastereoisomers, and characterized by elemental analyses, ESI-MS, and 1H NMR spectroscopy. The X-ray structures of 1a, 3a, and 5a show the involvement of two pyridine rings of two bpy ligands in strong intramolecular nonbonded ,,, interaction. The occurrence of a C,H···, interaction between an aromatic C,H and the ,-cloud of a pyridine ring leads to strong electronic shielding of this proton (1H NMR). In all cases, the two diastereoisomers show practically no differences in their absorption spectra, redox potentials, and pK values. The large shifts in the E1/2 values to less positive potentials and substantial redshifts in the MLCT bands that occur on deprotonation of 1, 3, and 5 are energetically correlated. From the profiles of E1/2(1), (2) vs. pH over the pH range 1,12, the equilibrium constants and standard redox potentials for all the complex species in the metal oxidation states II·II, II·III, and III·III and the bridged ligand in the protonation states H2pzbzim,, Hpzbzim2,, and pzbzim3, have been evaluated. Using these values the bond dissociation free energies for the benzimidazole N,H bonds have been estimated. Spectroelectrochemical studies have been carried out for 1a, 3a, and 5a in the range 400,1100 nm. With stepwise oxidation of the metal centers replacement of MLCT bands by LMCT bands occur gradually with the observation of sharp isosbestic points. In the case of 1a, a band observed at ,max = 910 nm for the RuIIRuIII species has been ascribed to intervalence charge transfer (IVCT) transition. [source]

Reactivity and X-ray Structural Studies in Ligand Substitution of [Cp/(Ind)Ru(dppf)Cl] , Epimerisation in [Cp/(Ind)Ru(Josiphos)Cl] {Cp = ,5 -C5H5, Ind = ,5 -C7H9, dppf = 1,1,-Bis(diphenylphosphanyl)ferrocene, Josiphos = (R)-(,)-1-[(S)-2-(Diphenylphosphanyl)ferrocenyl]ethyldicyclohexylphosphane}

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2007
Sin Yee Ng
Abstract Ligand substitution of [(Ind)Ru(PPh3)2Cl] (1) led to the isolation of [(Ind)Ru(PPh3){Ph2P(CH2)2C9H7}Cl] (2), [(Ind)Ru(dppf)Cl] (3) and [(Ind)Ru{(Ph2PCH2)3CMe}]PF6 ([4]PF6), and diastereoisomers [(R)- and (S)-(Ind)Ru(Josiphos)Cl] [(R)- 5 and (S)- 5], where (R)-(S)-Josiphos is the ferrocene-based chiral diphosphane ligand (R)-(,)-1-[(S)-2-(diphenylphosphanyl)ferrocenyl] ethyldicyclohexylphosphane. The Cp analogues of 5, viz. (R)- 6 and (S)- 6, were also obtained from [CpRu(PPh3)2Cl] (1a). Josiphos-dependent epimerisation was observed, with conversion of the (S) isomer to the (R) isomer in both cases. Chloride abstraction of 3 with NaPF6 in CH3CN and NaN3 in EtOH gave [(Ind)Ru(dppf)(CH3CN)]PF6 ([7]PF6) and [(Ind)Ru(dppf)(N3)] (8), respectively. The azido ligand in 8 underwent [3+2] dipolar cycloaddition with dimethyl acetylenedicarboxylate to give a N -bound bis(methoxycarbonyl)-1,2,3-triazolato complex, 9. X-ray crystal structures of the new complexes, except (R)- 5, (S)- 5 and (S)- 6, have been determined. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

Diastereopure Cationic NCN-Pincer Palladium Complexes with Square Planar ,4 - N,C,N,O Coordination

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 22 2006
Silvia Gosiewska
Abstract Neutral NCN-pincer palladium bromide complex 2 containing the monoanionic, enantiopure pincer ligand 2,6-bis{[(S)-2-hydroxymethyl-1-pyrrolidinyl]methyl}phenyl bromide (1) with bis- ortho -(S)-prolinol substituents was synthesized and isolated as a mixture of three stereoisomers [(SN,SN,SC,SC), (RN,SN,SC,SC), and (RN,RN,SC,SC)] in a 1:1:1 ratio. Upon abstraction of the bromide ion from the unresolved mixture of 2, single diastereoisomers of the cationic complexes [3]BF4 and [3]PF6, respectively, were formed with a unique,4 - N,C,N,O coordination mode of ligand 1. X-ray crystal structure determination established the intramolecular,4 - N,C,N,O coordination of 1 to palladium where the typical mer -,3 - N,C,N pincer coordination is accompanied by coordination of one of the hydroxy groups of the (S)-prolinol moieties. The water molecule that was cocrystallized in the crystal structure of [3]PF6 does not coordinate to palladium, but instead is involved in a hydrogen bonding network. The catalytic potential of both cationic complexes, [3]BF4 and [3]PF6, was tested in an aldol reaction of aldehydes with methyl isocyanoacetate to yield the oxazoline products as racemic mixtures.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]

Preparation of Optically Active ,-Amino[3]ferrocenophanes , Building Blocks for Chelate Ligands in Asymmetric Catalysis

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 23 2003
Patrick Liptau
Treatment of 1,1,-diacetylferrocene (4) with dimethylamine and TiCl4 yielded the unsaturated dimethylamino-substituted [3]ferrocenophane product 5. Its catalytic hydrogenation gave the corresponding saturated [3]ferrocenophane system 6 (trans/cis , 7:1). The rac -[3]ferrocenophane amine 6 was partially resolved (to ca. 80% ee) by means of L - or D - O,O, -dibenzoyltartrate salt formation. Treatment of 4 with the pure (R)- or (S)-methyl(1-phenylethyl)amine (8)/TiCl4 gave the corresponding optically active unsaturated [3]ferrocenophane amines (R)-(+)- 9 and (S)-(,)- 9, respectively. Their catalytic hydrogenation again proceeded trans -selectively, giving the corresponding saturated diastereomeric [3]ferrocenophane amines (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [starting from (R)- 9], their enantiomers ent - 10a and ent - 10b were obtained from (S)- 9, but with a poor asymmetric induction (10a/10b < 2:1). Quaternization of 6 (CH3I) followed by amine exchange using (R)- or (S)-methyl(1-phenylethyl)amine (8), respectively, proceeded with overall retention. Subsequent chromatographic separation gave the pure diastereoisomers (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [from (R)- 8, ent - 10a and ent - 10b from (S)- 8] in > 60% yield. Subsequently, the benzylic (1-phenylethyl) auxiliary was removed from the nitrogen atom by catalytic hydrogenolysis to yield the enantiomerically pure (> 98%) ([3]ferrocenophanyl)methylamines (1R,3R)- 11 and (1S,3S)- 11, respectively, which were converted into the corresponding dimethylamino-substituted [3]ferrocenophanes (1R,3R)- 6 and (1S,3S)- 6. Each enantiomer from the following enantiomeric pairs was isolated in its pure form and characterized by X-ray diffraction: (R)- 9/(S)- 9; (1R,3R,5R)- 10a/(1S,3S,5S)- 10a; (1R,3R,5S)- 10b/(1S,3S,5R)- 10b; (1R,3R)- 11/(1S,3S)- 11. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Synthesis and Dynamic Features of (Chloro)zirconocene Cations Stabilised by Pendant (Diarylphosphanyl)alkyl and (Dimethylamino)alkyl Substituents at Their Cyclopentadienyl Ring Systems

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 8 2003
Steve Döring
Abstract Treatment of the substituted (diarylphosphanyl)methyl group-4 metallocene complexes [(C5H4,CR1R2,PAr2)2ZrCl2] (2: R1/R2 = CH3/CH3, H/CH3, H/aryl) with Li[B(C6F5)4] in dichloromethane solution results in chloride ligand abstraction (with LiCl precipitation) to yield the complexes [(C5H4,CR1R2,PAr2)2Zr,Cl+] (5), with both phosphanyl groups internally coordinated to the metal centre. Three possible diastereoisomers are observed in the case of 5c (R1 = H; R2 = CH3), while bulkier R2 substituents give higher selectivities. The thermally induced (reversible) cleavage of the Zr,phosphane linkage results in dynamic NMR behaviour. Gibbs activation energies of ,G,(298 K) = 14.8 ± 0.5 and 14.5 ± 0.5 kcal/mol were obtained for these intramolecular equilibration processes in the complexes trans - 5d (R1 = H; R2 = Ph) and trans - 5e (R1 = H; R2 = ferrocenyl), respectively. Treatment of the substituted (dimethylamino)methyl metallocene complexes [(C5H4,CR1R2,NMe2)2ZrCl2] (6a, 6b) with Li[B(C6F5)4] proceeds analogously to yield the cation systems [{C5H4,C(CH3)2,NMe2}2ZrCl+] (12a) and [{C5H4,CH(CH3),NMe2}2ZrCl+] (12b, three possible diastereoisomers). Both complexes have their pairs of amino groups coordinated to the metal centre. The complexes exhibit dynamic NMR spectra. Selective equilibration of the diastereotopic N(CH3)A(CH3)B resonances of complex 12a is observed [,G,(233 K) = 11.5 ± 0.2 kcal/mol], whereas the adjacent C(CH3)A(CH3)B methyl groups remain diastereotopic. The dynamic equilibration of the latter was observed at a markedly higher temperature [,G,(333 K) = 17.3 ± 0.2 kcal/mol]. Treatment of [{C5H4,C(CH3)2,NMe2}CpZrCl2] (10) with Li[B(C6F5)4] resulted in the formation of complex [{C5H4,C(CH3)2,NMe2}CpZr,Cl+] (11), which shows the internal ,N(CH3)A(CH)B equilibration proceeding with a markedly higher activation barrier [,G,(333 K) = 17.6 ± 0.2 kcal/mol] than in 12a, and a stereochemical memory effect indicative of solvent coordination to the metal centre of the resulting highly electrophilic chlorozirconocene cation intermediate. Complex 11 was characterised by an X-ray crystal structure analysis, which shows the internal Zr,amine coordination. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Fluorinated Analogues of Amicetose and Rhodinose , Novel Racemic and Asymmetric Routes

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 7 2009
Jonathan M. Percy
Abstract Trifluoroethanol was converted into difluorinated (racemic) analogues of amicetose and rhodinose by metallated difluoroenol acetal chemistry, protection, release of the latent difluoromethyl ketone, stereoselective reduction and ozonolysis in acidic methanol. A fortuitous separation of diastereoisomers allowed the diastereoisomeric pyranoses to be obtained cleanly. Though reductive defluorination allowed a facile entry to the route, the corresponding monofluoro sugar analogues could not be separated. Instead, Sharpless asymmetric epoxidation followed by epoxide ring-opening with an unusual nucleophilic fluoride source allowed enantiomerically highly enriched and selectively protected fluorodiols to be obtained. Ozonolysis then afforded the methyl pyranosides, which could be transformed in a number of ways. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Synthesis and Electrochemical Studies of New Antimalarial Endoperoxides

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2003
Fadia Najjar
Abstract Structural analogues of endoperoxides belonging to the family of G factors have been synthesized under Mannich-type conditions. The structures of the different diastereoisomers have been established from NMR spectroscopic data. Their cathodic peak potentials have been determined by thin layer electrochemistry under potentiostatic conditions, and compared to artemisinin. These endoperoxides were evaluated in vitro against Plasmodium falciparum and showed moderate to good activity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Reactions of Di(tert -butyl)diazomethane with Acceptor-Substituted Ethylenes,

HELVETICA CHIMICA ACTA, Issue 5 2007
Rolf Huisgen
Abstract Di(tert- butyl)diazomethane (4) is a nucleophilic 1,3-dipole with strong steric hindrance at one terminus. In its reaction with 2,3-bis(trifluoromethyl)fumaronitrile ((E)- BTE), a highly electrophilic tetra-acceptor-substituted ethene, an imino-substituted cyclopentene 9 is formed as a 1,:,2 product. The open-chain zwitterion 10, assumed as intermediate, adds the second molecule of (E)- BTE. The 19F- and 13C-NMR spectra allow the structural assignment of two diastereoisomers, 9A and 9B. The zwitterion 10 can also be intercepted by dimethyl 2,3-dicyanofumarate (11) and furnishes diastereoisomeric cyclopentenes 12A and 12B; an X-ray-analysis of 12B confirms the ,mixed' 1,:,1,:,1 product. Competing is an (E)- BTE -catalyzed decomposition of 4 to give 2,3,4,4-tetramethylpent-1-ene (7)+N2; the reaction of (E)- BTE with a trace of water appears to be responsible for the chain initiation. The H2SO4 -catalyzed decomposition of diazoalkane 4, indeed, produced the alkene 7 in high yield. The attack on the hindered diazoalkane 4 by 11 is slower than that by (E)- BTE; the zwitterionic intermediate 21 undergoes cyclization and furnishes the tetrasubstituted furan 22. In fumaronitrile, electrophilicity and steric demand are diminished, and a 1,3-cycloaddition produces the 4,5-dihydro-1H -pyrazole derivative 25. The reaction of 4 with dimethyl acetylenedicarboxylate leads to pyrazole 29+isobutene. [source]

Reactions of Methyl Diazoacetate with (E)- and (Z)-1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile: Novel and Unanticipated Pathways,

HELVETICA CHIMICA ACTA, Issue 1 2007
Rolf Huisgen
Abstract The cycloadditions of methyl diazoacetate to 2,3-bis(trifluoromethyl)fumaronitrile ((E)- BTE) and 2,3-bis(trifluoromethyl)maleonitrile ((Z)- BTE) furnish the 4,5-dihydro-1H -pyrazoles 13. The retention of dipolarophile configuration proceeds for (E)- BTE with >,99.93% and for (Z)- BTE with >,99.8% (CDCl3, 25°), suggesting concertedness. Base catalysis (1,4-diazabicyclo[2.2.2]octane (DABCO), proton sponge) converts the cycloadducts, trans - 13 and cis - 13, to a 94,:,6 equilibrium mixture (CDCl3, r.t.); the first step is N -deprotonation, since reaction with methyl fluorosulfonate affords the 4,5-dihydro-1-methyl-1H -pyrazoles. Competing with the cis/trans isomerization of 13 is the formation of a bis(dehydrofluoro) dimer (two diastereoisomers), the structure of which was elucidated by IR, 19F-NMR, and 13C-NMR spectroscopy. The reaction slows when DABCO is bound by HF, but F, as base keeps the conversion to 22 going and binds HF. The diazo group in 22 suggests a common intermediate for cis/trans isomerization of 13 and conversion to 22: reversible ring opening of N -deprotonated 13 provides 18, a derivative of methyl diazoacetate with a carbanionic substituent. Mechanistic comparison with the reaction of diazomethane and dimethyl 2,3-dicyanofumarate, a related tetra-acceptor-ethylene, brings to light unanticipated divergencies. [source]

A New 2H -Azirin-3-amine as a Synthon for 2-Methylaspartate

HELVETICA CHIMICA ACTA, Issue 11 2005
Kathrin
The synthesis of a novel 2,2-disubstituted 2H -azirin-3-amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme,2). In 11, each of the protecting groups was removed selectively (Scheme,3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1-(naphthalen-1-yl)ethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme,2). However, the diastereoisomers of the synthons 3b and 3c could not be separated by chromatography. [source]

Spirocyclic Ethers Related to Ambrox®: Synthesis and Structure-Odor Relationships

HELVETICA CHIMICA ACTA, Issue 7 2004
Beat Winter
The seven spirocyclic ethers 4,10, related to the tricyclic odorant Ambrox,® (1) and its diastereoisomers 2 and 3, were synthesized. Their odoriferous activity/inactivity was correlated with the steric accessibility of the ether O-atom, calculated by computer-aided molecular modeling. The olfactory properties of the active compounds are discussed. [source]

The Nonchiral Bislactim Diethoxy Ether as a Highly Stereo-Inducing Synthon for Sterically Hindered, , -Branched , -Amino Acids: A Practical, Large-Scale Route to an Intermediate of the Novel Renin Inhibitor Aliskiren

HELVETICA CHIMICA ACTA, Issue 8 2003
Richard Göschke
The diastereoselective synthesis of the sterically hindered, , -branched , -amino acid derivative (2S,4S)- 24a and its N -[(tert -butoxy)carbonyl](Boc)-protected alcohol (2S,4S)- 19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)- 17 was obtained by alkylation of the chiral Schöllkopf dihydropyrazine (R)- 12a with the dialkoxy-substituted alkyl bromide (R)- 11a, which proceeded with explicitly high diastereofacial selectivity (ds ,98%) to give (2S,5R,2,S)- 13a (Scheme,4), followed by mild acid hydrolysis and N -Boc protection (Scheme,5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)- 11a with the enantiomeric (S)- 12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeOC(6) and the bulky residues of (R)- 11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)- 11a was found to provide a 95,:,5 mixture of diastereoisomers (2S,2,S)- 22a and (2R,2,S)- 23a in high yield (Scheme,6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)- 24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)- 28a and (R)- 28b with both (R)- 12a and (S)- 12b as well as with the achiral 21 was investigated (Schemes,7,9). The precursor bromides (R)- 11a, (S)- 11b, (R)- 28a, and (S)- 28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)- 7a and (S)- 7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes,3 and 7). A practical and economical protocol of the preparation of (2S,4S)- 24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N -protected , -branched , -amino acid with (2S) absolute configuration. [source]

Synthesis and Reactions of Enantiopure Substituted Benzene cis -Hexahydro-1,2-diols

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2010
R. Boyd
Abstract Enantiopure cis -dihydro-1,2-diol metabolites, obtained from toluene dioxygenase-catalysed cis -dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis -hexahydro-1,2-diol derivatives by catalytic hydrogenation via their cis -tetrahydro-1,2-diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis -dihydro-1,2-diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis -hexahydro-1,2-diol products have been unequivocally established by X-ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis -hexahydro-1,2-diol diastereoisomers, to desymmetrise a meso - cis -hexahydro-1,2-diol and to synthesise 2-substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors. [source]

Facile Synthesis of Enantiopure 4-Substituted 2-Hydroxy-4- butyrolactones using a Robust Fusarium Lactonase

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2009
Bing Chen
Abstract A facile chemo-enzymatic process has been developed for producing stereoisomers of 4-substituted 2-hydroxy-4-butyrolactones with good to excellent enantioselectivity. This process involves an easy separation of the diastereoisomers by column chromatography and efficient enzymatic resolution by whole cells of Escherichia coli JM109 expressing Fusarium proliferatum lactonase gene. This biocatalyst shows strong tolerance towards different substrate structures and at least three out four possible isomers could be obtained in excellent enantiomeric purity. Different substrate concentrations (10,mM,200,mM) were examined, giving a substrate to catalyst ratio of up to 26:1. This general and efficient enzymatic process provides access to stereoisomers of 4-substituted 2-hydroxy-4-butyrolactones readily and cost-effectively. The stereochemical assignments were conducted systematically based on NMR, X-ray diffraction and circular dichroism, leading to further understanding of the enzyme's stereoselectivity. [source]

Pirouetting in chiral [2]catenanes,

ISRAEL JOURNAL OF CHEMISTRY, Issue 2 2007
Seogshin Kang
One of the best known classes of mechanically interlocked molecules is the category of [2]catenanes, which exhibit donor-acceptor interactions between the 1,5-dioxynaphthalene (DNP) units in a crown ether and the bipyridinium units in the tetracationic cyclophane, cyclobis(paraquat- p -phenylene) (CBPQT4+). In order to gain an in-depth understanding and appreciation of the stereochemistry and dynamic behavior of these [2]catenanes, chiral analogues,having both the DNP ring, which is capable of displaying planar chirality, and the axially chiral binaphthol (BINAP) moiety (as both enantiomers and as the racemic modification), in a crown ether, in addition to the CBPQT4+ cyclophane,have been synthesized using a template-directed protocol. Dynamic 1H NMR spectroscopy shows that (i) the presence of immutable axial chirality, arising from the BINAP moiety in the crown ether component, leads to no induction of diastereoselectivity,the chiral catenanes exist as a mixture of diastereoisomers in solution at low temperatures in the approximate ratio of 1:1, (ii) the barrier (,GcD,) to the interconversion between these two diastereoisomers is 7.9 ± 0.1 kcal mol,1 at 171 K, and (iii) no induction of diastereoselectivity is observed upon the addition of a chiral solvating agent to the chrial catenanes. The pattern of behavior in the variable temperature 1H NMR spectra and the low ,TGcD, value indicates that the dynamic process involving the interconversion between these two diastereoisomers is one of a pirouetting nature. Of the four possible diastereoisomers, only two, (R)-(pR/pS) or (S)-(pR/pS), are shown to exist in solution. [source]