Reaction of catalytic enantioselective reductive aminolysis of δ2-oxazolin-5-ones as a method of asymmetric synthesis of α-amino acids

This investigation is devoted to the interaction of Δ²-oxazolin-5-ones, S(—)-α-phenylethy lamine and H₂ in the presence of PdCl₂ which yields α-phenylethylamides of acylamino acids of the S,S configuration, hydrolysis of the latter compounds resulting in the formation of optically pure amino acids and providing for chiral amine recycling. In DME, double bond saturation and ring opening in Δ²-oxazolin-5-one occur within the catalytic complex sphere without the intermediate formation of saturated oxazolinones or unsaturated amides. In t-BuOH, saturated oxazolinones are formed as intermediates. The catalyst formed in situ was shown to be a zero-valent Pd complex with S(—)-α-phenylethylamine stabilized by substrate coordination. The stereochemical pathway of the reactions has been traced. Reductive aminolysis involves cis-addition of H₂, while in reductive methanolysis H₂ trarns-addition occurs. The suggested process mechanism accounts for the ratio of aminolysis and racemization rates for saturated oxazolinones and the ratio of diastereomers of α-phenylethylamides of acylamino acids obtained by reacting unsaturated Δ²oxazolin-5-ones with S(—)-α-phenyl-ethylamine. In agreement with the postulated mechanism, the catalyst enantioselectivity is observed at the steps of substrate addition to the catalyst and proton transfer to the α-C-center, provided the process is carried out in DME. In the case of t-BuOH, the enantiodifferentiating action of the catalyst vanishes as a result of racemization, and process stereo selectivity appears at the step of saturated oxazolinone aminolysis with a chiral amine.     

Single-center vs. multi-center post-metallocene catalysts for propylene polymerization

The structural characteristics of polypropylene samples prepared with two post-metallocene catalysts based on complexes bis-{M-(3,5-di-tert-butyl-salicylidene)-4-[bis-(5-methyl-2-furyl)methyl]aniline}titanium dichloride and [(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra(pentafluorophenyl)-1,3-dioxalan-4,4-dimethanol)titanium dichloride are investigated by GPC, ¹³C NMR, IR, DSC, and XRD methods. A combination of the first complex and MAO forms a single-center catalyst which polymerizes propylene to a nearly perfectly atactic polymer. A combination of the second complex and MAO forms a multi-center catalyst system producing polymer mixtures with broad molecular weight distributions containing five to six Flory components with different average molecular weights. Relative contents of the Flory components strongly depend on the type of solvent in the polymerization reactions. Some of the active centers produce high molecular weight, highly isotactic crystalline material with the melting point over 154 °C. The nature of steric errors in these polymer fractions (determined by ¹³C NMR) can be explained by a variant of stereocontrol similar to that exerted by metallocene catalysts of the C₁ symmetry.     

Synthesis and decarboxylation of N-acyl-α-triphenylphosphonio-α-amino acids: a new synthesis of α-(N-acylamino)alkyltriphenylphosphonium salts

4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF₄ at room temperature to give N-acyl-α-triphenylphosphonioglycines 3 (R² = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones 2 react with water in CH₂Cl₂/THF solution without any acidic catalyst at 0-5 °C in a few days yielding N-acyl-α-triphenylphosphonio-α-amino acids 3 (R² = Me) or α-(N-acylamino)alkyltriphenylphosphonium salt 4 (R² = CH₂OMe). α-Triphenylphosphonio-α-amino acids 3, on heating up to 105-115 °C under reduced pressure (5 mmHg) or on treatment with diisopropylethylamine in CH₂Cl₂ at 20 °C undergo decarboxylation to give the corresponding α-(N-acylamino)alkyltriphenylphosphonium salts 4, usually in very good yields.     

Indenyl and fluorenyl transition metal complexes: XIV. Synthesis and reactions of chromium tricarbonyl complexes of 5,10-dihydroindeno[2,1-α]indene

1-4,4a,10b-η⁶-5,10-dihydroindeno[2,1-α]indene chromium tricarbonyl (III) has been obtained by Rausch's method. Deprotonation of III by t-BuOK in THF solution, by potassium solution in HMPTA or by KH in THF at −65°C yields an η⁶-anion IV, which is irreversibly rearranged into η⁵-anion V at 20°C. Action of n-BuLi/t-BuOK mixture in THF at −65°C results in the formation of η⁶-dianion VI, which is irreversibly converted into η⁵-dianion VII above 0°C. Alkylation of IV with benzyl iodide yields 5-exo-benzyl(III). Reaction of V with benzyl iodide leads to the σ-benzyl derivative, which is isomerized into 5-endo-benzyl(III). The reaction of V with N-nitroso-N-methyltosylamide yields the η⁵-nitrosodicarbonyl complex of chromium (XI).     

Mechanistic studies on the Pd–Cl cleavage of dichloro-[1-alkyl-2-(naphthylazo)imidazole]palladium(II) complexes by 8-quinolinol

8-Quinolinol (HQ) reacts with [Pd(α-/β-NaiR)Cl₂] [α-/β-NaiR = 1-alkyl-2-(naphthyl-α-/β-azo)imidazole] in acetonitrile (MeCN) solution to give [Pd(α-/β-NaiR)(Q)](ClO₄). The products are characterized by spectroscopic techniques (FT-IR, UV–Vis, NMR). The reaction kinetics show a first order dependence of rate on each of the concentration of the metal complex and HQ. Addition of LiCl to the reaction retarded the rate of reaction and has proved the cleavage of the Pd–Cl bond as the rate-determining step. Thermodynamic parameters (Δ^‡H^° and Δ^‡S^°) are determined from variable temperature kinetic studies. The magnitude of the second order rate constant, k₂, increases as in the order: Pd(NaiEt)Cl₂ < Pd(NaiMe)Cl₂ < Pd(NaiBz)Cl₂ as well as Pd(β-NaiR)Cl₂ < Pd(α-NaiR)Cl₂.     

Resolution of 1-n-propoxy-3-methyl-3-phospholene 1-oxide by diastereomeric complex formation using TADDOL derivatives and calcium salts of O,O′-dibenzoyl-(2R,3R)- or O,O′-di-p-toluoyl-(2R,3R)-tartaric acid

1-n-Propoxy-3-methyl-3-phospholene 1-oxide was prepared in optically active form by extending resolution methods applying (−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane (‘TADDOL’) and (−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol (‘spiro-TADDOL’), as well as the acidic and neutral Ca²⁺ salts of (−)-O,O′-dibenzoyl- and (−)-O,O′-di-p-toluoyl-(2R,3R)-tartaric acid. In one case, the diastereomeric complex could be identified by single crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by CD spectroscopy.     

Multiple Diastereomers of [M n+(α m -P2W17O61)2](20−n)− (M=UIV, ThIV, CeIII; m=1, 2). Syn- and Anti-Conformations of the Polytungstate Ligands in α1α1, α1α2, and α2α2 Complexes

Several examples of the complexes, [M(P₂W₁₇O₆₁)₂] ^n? (M=U^IV, Th^IV, Ce^III), containing both α ₁ (C ₁) and α ₂ (C _s ) isomers of the tungstophosphate ligands, have been synthesized and characterized by X-ray crystallography and ³¹P NMR spectroscopy. In every case the heteroatom M has the anticipated square antiprism coordination. When both ligands are α ₂ (the U^IV and Ce^III complexes) the solid state structure adopts a syn-conformation of the ligands, as had been previously demonstrated for M=Ce^IV and Lu^III; in solution a single set of P-NMR lines is observed, consistent with a single unique structure or rapid interconversion of syn- and anti-forms. When one or both ligands are α ₁ (Uα ₁ α ₁, Uα ₁ α ₂, Thα ₁ α ₁, Ceα ₁ α ₂) multiline P-NMR spectra reveal the presence of two major diastereomers in solution, presumably the syn- and anti-forms. In the solid state, crystals of ammonium or potassium salts of the U and Ce complexes contain anti-conformers, while the Th complex proves to be syn. Variable temperature (～25–～60°C) P-NMR spectroscopy of solutions of the Uα ₁ α ₁ complex reveals the onset of syn-anti interconversion together with the irreversible formation of minor amounts of other diastereomers generated by dissociation and scrambling of the enantiomers of the polytungstate ligands.     

Arene substitution by iridium complexes under mild conditions

[(C₅Me₅Ir)₂Cl₄] reacts with Al₂Me₆ in saturated hydrocarbons to give [C₅Me₅IrMe₄) or cis- and trans-[C₅Me₅Ir)₂Me₂(α-CH₂)₂], depending on workup conditions. In benzene or toluene solution the main product is [(C₅Me₅Ir)₂Me(Aryl)(α-CH₂)₂] (aryl = Ph or m- plus p-tolyl, ratio 2/1); if CO is introduced into the benzene solution the products are [C₅Me₅Ir(CO)R¹R²] (R¹ = Me, R² = Ph; R¹ = R² = Me or Ph).     

Influence of the polyether chain on the dissociation of “living” polymers obtained in the anionic polymerization of ethylene oxide

Conductivity studies were carried out on block copolymers of composition K⁺, ?(EO)_n- αMeSt-(St)_x -αMeSt-(EO)_n^?, K⁺, where n = 1–5 or 20, in THF. The conductivity of the solutions exhibits a strong tendency to increase as n is raised up to 3, and to change only slightly on further extension of the polyether chain. An equilibrium between ion pairs and free ions is established in the solution only when n is 1 or 2; for n ? 3, ion triplets are formed also. The dissociation constants for the ion pairs and the ion triplets and their temperature dependence were determined. The formation of ion triplets, as well as the changes in dissociation of the ion species on extending the polyether block, are explained by solvation of the counter-ion by the polyether chain.     

Stereoselective conjugate addition reactions of lithium amides to α,β-unsaturated chiral iron acyl complexes [(η-C5H5)Fe(CO)(PPh3)(COCHCHR)]

Conjugate addition of achiral lithium dimethylamide to the chiral iron cinnamoyl complexes (S,E)- and (S,Z)-[(η⁵-C₅H₅)Fe(CO)(PPh₃)(COCHCHPh)] proceeds with high diastereoselectivity, with this protocol being used to establish unambiguously the absolute configuration of Winterstein’s acid (3-N,N-dimethylamino-3-phenylpropanoic acid) as (R). The highly diastereoselective conjugate addition of lithium N-benzyl-N-trimethylsilylamide to a range of α,β-unsaturated iron acyl complexes, followed by in-situ elaboration of the derived enolate by either alkylation or aldol reactions is also demonstrated, facilitating the stereoselective synthesis of both cis- and trans-β-lactams. This methodology has been used to effect the formal asymmetric syntheses of (±)-olivanic acid and (±)-thienamycin. Addition of chiral lithium amides derived from primary and secondary amines to the iron crotonyl complex [(η⁵-C₅H₅)Fe(CO)(PPh₃)(COCHCHMe)] indicates that lithium N-α-methylbenzylamide shows low levels of enantiorecognition, while lithium N-3,4-dimethoxybenzyl-N-α-methylbenzylamide and lithium N-benzyl-N-α-methylbenzylamide show high levels of enantiodiscrimination. The high level of observed enantiorecognition was used to facilitate a kinetic resolution of (RS)-[(η⁵-C₅H₅)Fe(CO)(PPh₃)(COCHCHMe)] with homochiral lithium (R)-N-3,4-dimethoxybenzyl-N-α-methylbenzylamide. Further mechanistic studies show that conjugate additions of (RS)-lithium N-benzyl-N-α-methylbenzylamide to either the (RS)- or homochiral iron crotonyl complex show 2:1 stoicheiometry, while homochiral lithium N-benzyl-N-α-methylbenzylamide shows 1:1 stoicheiometry.     

New cup-shaped α-cyclodextrin derivatives and a study of their catalytic properties in oxidation reactions

A series of new α-cyclodextrin derivatives with a substituted propylene bridge attached to the 6-O's of the A,D-glucose units are reported. The compounds were prepared from the known 6^A,6^D-di-O-(prop-2-methylidene-1,3-dienyl)-hexadeca-O-benzyl-α-cyclodextrin, which was transformed into 6^A,6^D-di-O-(prop-2-methyl-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-formyl-2-hydroxy-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-aminomethyl-2-hydroxy-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-hydroxymethylidene-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-formyl-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-carboxy-1,3-dienyl)-α-cyclodextrin and 6^A,6^D-di-O-(prop-2-methoxycarbonyl-1,3-dienyl)-α-cyclodextrin. The new compounds were evaluated for their ability to affect amine and alcohol oxidations in the presence of hydrogen peroxide.     

Sequential injection lab-on-valve simultaneous spectrophotometric determination of trace amounts of copper and iron

A sequential injection (SI) method in a lab-on-valve (LOV) format for simultaneous spectrophotometric determination of copper and iron has been devised. The detection chemistry is based on the complex formation of 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]aniline (5-Br-PSAA) with copper(II) and/or iron(II) at pH 4.6. Copper(II) reacts with 5-Br-PSAA to form the complex which has an absorption maximum at 580 nm but iron(III) does not react. In the presence of a reducing agent only iron(II)-5-Br-PSAA complex is formed and detected at 558 nm. Under the optimum experimental conditions, the determinable ranges are 0.1-2 mg l⁻¹ for copper and 0.1-5 mg l⁻¹ for iron, respectively, with a sampling rate of 18 h⁻¹. The limits of detection are 50 μg l⁻¹ for copper and 25 μg l⁻¹ for iron. The relative standard deviations (n = 15) are 2% for 0.5 mg l⁻¹ copper and 1.8% for 0.5 mg l⁻¹ iron when determined in standard solutions. The recoveries range between 96 and 105% when determining 0.25-2 mg l⁻¹ of copper and 0.2-5 mg l⁻¹ of iron in artificial mixtures at copper/iron ratios of 1:10 to 5:1. The proposed SI-LOV method is successfully applied to the simultaneous determination of copper and iron in multi-element standard solution and in industrial wastewater samples.     

Die Komplexbildung der neutralen Amidgruppe mit Cu2+ in wässeriger Lösung

The interaction between Cu²⁺ and the terdentate ligands N-picolinoyl-ethylenediamine, glycine-2-pyridylmethylamide, N^α-(2-pyridylmethyl)-glycinamide and N^α-(2-pyridylmethyl)-glycine-ethylamide, respectively, has been studied by spectrophotometry and potentiometry. At high pH values the ionised amide group undergoes complex formation and the resulting chelates have similar structures and stabilities. In slightly acidic solution however, each ligand gives rise to a different species. These facts are explained by assuming that the neutral amide group coordinates through its carbonyl oxygen atom. The stability constant and the absorption spectrum of each complex have been calculated by computer programmes.     

Efficient solid-state microwave-promoted complexation of a mixed dioxa-diaza macrocycle with an alkali salt. Synthesis of a sodium ethyl 4-benzeneazophosphonate complex

The first example of microwave-promoted solid-state synthesis of an alkali complex derived from a heteromacrocyclic compound has been described. The 15-membered mixed dioxa-diaza macrocycle 5,6,14,15-dibenzo-1,4-dioxa-8,12-diazacyclopentadeca-5,14-diene (L) by reaction with sodium ethyl [4-α-(benzeneazoanilino)-N-benzyl]phosphonate (NaEP · 1.5H₂O) yielded the sodium complex [Na(L)(μ-EP) · H₂O]₂, as a diphosphonate-bridged dinuclear species. The new complex was identified and characterized on the basis of elemental and thermal (TG and DTA) analyses as well as by IR, ¹H and ¹³C nuclear magnetic resonance, and ESI and LDI mass spectroscopic studies. The results obtained by the reaction carried out under focused microwave conditions are compared with those obtained by conventional thermal reactions, both in the solid-state and in solution.     

Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of <Emphasis Type="Italic">endo</Emphasis>-ethenotetrahydrothebaine and their behavior in the heck reaction

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C⁷-C⁸ bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.     

The effect of the solvent in the nitrate-selective electrode

An organoboron reagent, 2-[1(o-dihydroxyborylphenyl)-2-phenylethyl]-2-imidazoline hydrochloride, is used for the determination of tartaric acid in aqueous solution. The complex of tartaric acid with the organoboron reagent can be extracted into an organic solvent and determined spectrophotometrically in the concentration range 10^-5–lO^-4 M, with a relative standard deviation of ca. 5%. Alternatively, the complex can be determined turbidimetrically in the concentration range 2 × 10^-4–IO^-3 M with approximately the same precision.     

Stepwise solid phase synthesis of uridylylated viral genome-linked peptides using uridylylated amino acid building blocks

The uridylylated amino acid building blocks 2-cyanoethyl-(N^α-9-fluorenylmethoxy-carbonyl-tyrosin-4-yl)-(2′,3′-di-O-acetyluridin-5′-yl) phosphate and 2-chlorophenyl-(N^α-fluorenyl-methoxycarbonyl-serin-3-yl)-(2′,3′-di-O-acetyluridin-5′-yl) phosphate have been used successfully in an on-line SPPS of the VPgpU from the polio, coxsackie and cowpea mosaic virus.     

Structural analysis of photo-oxidized (ethylenediamine)bis(2,2′-bipyridine)ruthenium(II) complexes by using on-line electrospray mass spectrometry of labeled compounds

Photo-oxidation of Ru(bpy)₂(en)²⁺, where bpy = 2,2′-bipyridine, en = ethylenediamine, was studied in isotopic labeling experiments by using on-line electrospray mass spectrometry (ESMS). The complex was known to undergo photochemical dehydrogenation of a fourelectron oxidation, giving the α,α′-diimine complexes in a stepwise manner via a two-electron-oxidized intermediate that represents loss of two hydrogen atoms from the en ligand. On-line mass analysis after photoirradiation (λ > 420 nm) of Ru(bpy)₂(ed)²⁺ (ed = ethylene-d₄diamine) showed that the ligand of the intermediate with loss of two hydrogen atoms was not an enamine but had an imine structure. Also, a ligand-oxygenated complex that has mass 14 amu higher than the Ru(bpy)₂(en)²⁺ complex was observed in the ES mass spectra. The ligand of this complex was proposed to have a nitroso structure as a primary product in ¹⁸O₂ experiments. The oxygenated complex was not generated in a stepwise manner via the imine intermediate, but directly by loss of two amino hydrogen atoms and addition of an oxygen atom. The source of the oxygen atom would be from oxygen dissolved in solution rather than from water in solution. Another oxygenated complex Ru(bpy)₂(NO ₂ ^#x2212; )⁺ was produced by irradiation and the structure was identified in ¹⁸O₂ experiments.     

The steric course of proton elimination in conversion of a tricarbonylcyclohexadieneiron carbinol into an endocyclic cation

Tricarbonyl-1-carbomethoxy-5α²H-cyclohexadieneiron (3) reacts with MeLi to tricarbonyl-1(1¹ -hydroxy-1¹ -methyl-ethyl)-5α²H-cyclohexadiene- iron (1) which yields with acid the salt tricarbonyl-1(1¹ -methyl-ethyl)-5₂H- cyclohexadienyliron(+)-PF₆ (?) (4). Retention of ²H demonstrates the stereochemistry of the elimination of the ring proton as β-(endo).     

Sesquiterpenoids and norsesquiterpenoids from three liverworts

Six new sesquiterpenoids and two new norsesquiterpenoids were isolated from the essential oils of three liverworts. The isolated compounds include (+)-eudesma-4,11-dien-8α-ol from the liverwort Diplophyllum albicans, (−)-4β,5β-diacetoxygymnomitr-3(15)-ene, (+)-5β-acetoxygymnomitr-3(15)-ene, (−)-15-acetoxygymnomitr-3-ene, (−)-3β,15β-epoxy-4β-acetoxygymnomitrane, and (−)-3α,15α-epoxy-4β-acetoxygymnomitrane from Marsupella emarginata, and (+)-1,2,3,6-tetrahydro-1,4-dimethylazulene and (−)-2,3,3a,4,5,6-hexahydro-1,4-dimethylazulen-4-ol from Barbilophozia floerkei. These compounds were isolated by a combination of different chromatographic techniques, and their structures were determined by extensive spectroscopic studies (MS, ¹H, ¹³C, and 2D NMR) and chemical transformations using enantioselective GC.