Preparation of chiral alpha-oxy-[2H1]methyllithiums of 99% ee and determination of their configurational stability

(Tributylstannyl)methyl 2,2,6,6-tetramethylpiperidine-1-carboxylate was metalated with t-BuLi/TMEDA at -78 degrees C and borylated with the mixed borate derived from (R,R)-1,2-dicyclohexylethane-1,2-diol and t-butanol to give diastereomeric boronates 31/32 in equal amounts. Boronates 31 and 32 were reduced with LiBEt3D and then oxidized with basic H2O2 to give (S)- and (R)-tributylstannyl-[1-2H1]methanol of 99% ee, respectively. Treatment of their respective phosphates with n-BuLi at -78 and 0 degrees C gave microscopically configurationally stable phosphinyloxy-substituted [2H1]methyllithiums, which rearranged to hydroxy-[1-2H1]methylphosphonates of ee > 98% (phosphate-phosphonate rearrangement). The N,N-diisopropylcarbamates of the enantiomeric tributylstannyl-[1-2H1]methanols were transmetalated to give carbamoyloxy-substituted chiral [2H1]methyllithiums, which were macroscopically configurationally stable for prolonged periods of time (up to 3 h, ee still 99%) at -78 degrees C, deduced from trapping experiments with benzaldehyde. The chemical stability of these methyllithiums ended at -50 degrees C. The stereochemistry of the monoprotected and monodeuterated 1-phenylethane-1,2-diols obtained was secured by spectroscopic comparison of their Mosher esters with that of all four stereoisomeric 1-phenyl-[1-2H1]ethane-1,2-diols synthesized independently. Furthermore, the configurations of the boronates and the chiral methyllithiums derived from them were deduced from a single-crystal X-ray structure analysis of a carbamate in which the tributylstannyl group had been replaced by the [(1R)-menthyl]dimethylstannyl group.     

3-Aryl-5-[(aryloxy)methyl]-3-[(1H-1,2,4-triazol-1-yl)methyl]-2-methylisoxazolidine derivatives. Synthesis and antifungal activity

The synthesis and antifungal activity of a novel series of 3-aryl-5-[(aryloxy)methyl]-3-[(1H-1,2,4-triazol-1-yl)-methyl]-2-methylisoxazolidines are described. The in vitro activity was evaluated in solid agar cultures against a variety of dermatophytes and yeast fungi, while in vivo activity was measured in an immune-compromised mouse model of systemic candidiasis. The activity of the title series was compared to that of ketoconazole and one derivative, the cis-3-(4-chlorophenyl)-5-(4-chlorophenyloxy)methyl analogue 5f was found to possess a similar potency in the in vivo assay. Structure-activity relationship correlations are also discussed.     

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.     

Syntheses and properties of 2-[(dimethylamino)methyl]-1-hydroxyferrocene and its derivatives

A 1,2-disubstituted ferrocene derivative, 2-[(dimethylamino)methyl]-1-hydroxyferrocene (I), was prepared from 2-[(dimethylamino)methyl]-1-iodoferrocene via 2-[(dimethylamino)methyl]-1-acetoxyferrocene. On complexation, compound I served as a stable monovalent chelate ligand of a 1,2-disubstituted ferrocene derivative. In addition, a dihydroxy derivative, 2-(hydroxymethyl)-1-hydroxyferrocene, was obtained from hydrolysis of the methiodide formed from I.     

苯甲酸（1H－1，2，4－三唑－1－基）－3，3－二甲基－2－丁酮酯衍生物的合成

用冠醚作催化剂，通过苯甲酸盐同１－溴代－１－（１Ｈ－１，２，４－三唑－１－基）－３．３－二甲基丁酮－２－反应，合成了一系列苯甲酸（１Ｈ－１，２，４－三唑－１－基）－３，３－二甲基－２－丁酮酯类新化合物，并对合成方法进行了探讨。通过ＩＲ、￣１ＨＮＭＲ及元素分析，确定了化合物的结构。     

Synthesis of 1-[(1,2-dithiol-3-ylidene)methyl]pyrrolo[1,2-a]pyrazines and 2-[(1,2-dithiol-3-ylidene)methyl]pyridines from 1,2-dithiole-3-thiones

Benzo- and pyridoannulated 1,2-dithiole-3-thiones react with compounds containing an activated methyl group such as 1-methyl-3,4-dihydropyrrolo[1,2-a]pyrazine and 2-methylpyridines to furnish substituted 1,2-dithiol-3-ylidenes.     

Molecular structures of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate and methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate

The structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate is determined by X-ray crystallography and further used to elucidate the structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate, using the data of homo- and heteronuclear 2D NMR correlation spectroscopy.     

(13)C,(13)C]- and [(13)C,(1)H]-TROSY in a triple resonance experiment for ribose-base and intrabase correlations in nucleic acids.

A novel TROSY (transverse relaxation-optimized spectroscopy) element is introduced that exploits cross-correlation effects between (13)C-(13)C dipole-dipole (DD) coupling and (13)C chemical shift anisotropy (CSA) of aromatic ring carbons. Although these (13)C-(13)C effects are smaller than the previously described [(13)C,(1)H]-TROSY effects for aromatic (13)C-(1)H moieties, their constructive use resulted in further transverse relaxation-optimization by up to 15% for the resonances in a 17 kDa protein-DNA complex. As a practical application, two- and three-dimensional versions of the HCN triple resonance experiment for obtaining ribose-base and intrabase correlations in the nucleotides of DNA and RNA (Sklenar, V.; Peterson, R. D.; Rejante, M. R.; Feigon, J. J. Biomol. NMR 1993, 3, 721-727) have been implemented with [(13)C,(1)H]- and [(13)C,(13)C]-TROSY elements to reduce the rate of transverse relaxation during the polarization transfers between ribose (13)C1' and base (15)N1/9 spins, and between (13)C6/8 and N1/9 within the bases. The resulting TROSY-HCN experiment is user-friendly, with a straightforward, robust experimental setup. Compared to the best previous implementations of the HCN experiment, 2-fold and 5-fold sensitivity enhancements have been achieved for ribose-base and intrabase connectivities, respectively, for (13)C,(15)N-labeled nucleotides in structures with molecular weights of 10 and 17 kDa. TROSY-HCN experiments should be applicable also with significantly larger molecular weights. By using modified TROSY-HCN schemes, the origins of the sensitivity gains have been analyzed.     

Crystal structure of 4,4-bipyridine-containing complexes of copper(II) nitrate with 1-[(2-Hydroxyethylimino)methyl]naphthalen-2-ol and 2-[(2-hydroxyethylimino)methyl]phenol

The crystal structures of (μ-4,4-bipyridine)-di(nitrato-1-[(2-hydroxyethylimino)methyl]naphthalen-2-olocopper (I) and catena-di(μ-4,4’-bipyridine)di(μ-4,4’-bipyridine)-di(nitrato-2-[2-(hydroxyethylimino) methyl]phenolocopper)diaquacopper(II) nitrate (II) were determined. In the crystal of I, each of the two copper atoms coordinates a singly deprotonated tridentate azomethine molecule, a nitrate ion, and bipyridine, which functions as a bridge between the central atoms. The copper coordination polyhedron is a slightly distorted tetragonal pyramid with the base formed by the imine and bipyridine nitrogen atoms and the phenol and alcohol oxygen atoms. The axial site in the pyramid is occupied by the oxygen atom of the monodentate nitrate groups. In the trinuclear structure II with C₂ crystal chemical symmetry, the terminal coordination unit is composed through copper coordination of monodeprotonated 2-[2-(hydroxyethylimino)methyl]phenol, bipyridine, and the nitrate anion. In the crystal, the trinuclear molecules form infinite ribbons along the z axis in which the pyridine molecules perform the bridging function. The central copper atom has an octahedral configuration formed by the nitrogen atoms of four 4,4’-bipyridine molecules and oxygen of two water molecules.     

Xenon Trioxide Adducts of O-Donor Ligands; [(CH3)2CO]3XeO3, [(CH3)2SO]3(XeO3)2, (C5H5NO)3(XeO3)2, and [(C6H5)3PO]2XeO3

Xenon trioxide (XeO₃) forms adducts with triphenylphosphine oxide, dimethylsulfoxide, pyridine-N-oxide, and acetone by coordination of the ligand oxygen atoms to the Xe^VI atom of XeO₃. The crystalline adducts were characterized by low-temperature, single-crystal X-ray diffraction, and Raman spectroscopy. Unlike solid XeO₃, which detonates when mechanically or thermally shocked, solid (C₅H₅NO)₃(XeO₃)₂, [(C₆H₅)₃PO]₂XeO₃, and [(CH₃)₂SO]₃(XeO₃)₂ are insensitive to mechanical shock. The [(CH₃)₂SO]₃(XeO₃)₂ adduct slowly decomposes over several days to (CH₃)₂SO₂, Xe, and O₂. All three complexes undergo rapid deflagration when ignited by a flame. Both [(C₆H₅)₃PO]₂XeO₃ and (C₅H₅NO)₃(XeO₃)₂ are room-temperature stable and the [(CH₃)₂CO]₃XeO₃ complex dissociates at room temperature to form a stable solution of XeO₃ in acetone. The xenon coordination sphere of [(C₆H₅)₃PO]₂XeO₃, a distorted square-pyramid, provides the first example of a five-coordinate XeO₃ complex with only two Xe- - -O adduct bonds. The xenon coordination spheres of the remaining adducts are distorted octahedra, comprised of three Xe- - -O secondary bonds that are approximately trans to the primary Xe−O bonds of XeO₃. Quantum-chemical calculations were used to assess the nature of the Xe- - -O adduct bonds, which are described as predominantly electrostatic bonds between the nucleophilic oxygen atoms of the bases and the σ-holes of the electrophilic xenon atoms.     

Sulfanilamide copper(II) chelates with 2-[(2-hydroxyphenyl-imino)methyl]phenolom and 1-[(2-hydroxyphenylimino)-methyl]naphthalen-2-ol

2-[(2-Hydroxyphenylimino)methyl]phenol (H²L¹) and 1-[(2-hydroxyphenylimino)methyl]naphthalen-2-ol (H²L²) reacted with copper(II) acetate hydrate and sulfanilamide (Sf¹), sulfathiazole (Sf²), sulfaethidole (Sf³), sulfadiazine (Sf⁴), and sulfadimidine (Sf⁵) in ethanol to give mixed-ligand copper chelates with the composition Cu(Sf^1–5)(L^1–2) · n H₂O (n = 1, 2). All these complexes are monomeric. Salicylaldehyde imines (H₂L¹ and H₂L²) behave as doubly deprotonated tridentate O,N,O ligands, whereas sulfanilamides (Sf^1–5) are unidentate ligands. Thermolysis of the synthesized complexes includes dehydration at 70–90°C, followed by complete thermal decomposition (290–380°C). The complexes [Cu(Sf¹)(L¹)] · 2H₂O and [Cu(Sf³)(L¹)] · H₂O at a concentration of 10⁻⁴ M inhibited growth and reproduction of 100% of human myeloid leukemia cells (HL-60). The inhibitory effect was 90 and 75%, respectively, at a concentration of 10⁻⁵ M, whereas no antitumor activity was observed at a concentration of 10⁻⁶ M.     

Synthesis and lanthanide coordination chemistry of 2-[(phosphinoyl)methyl]-4,5-dihydrooxazole and 2-[(phosphinoyl)methyl]benzoxazole ligands

Syntheses for [(diphenylphosphinoyl)methyl]-4,5-dihydrooxazole (2) and [(diarylphosphinoyl)methyl]benzoxazoles [aryl = phenyl (3), tolyl (4), 2-trifluoromethylphenyl (5) and 3,5-bis(trifluoromethyl)phenyl (6)] have been developed. Each ligand has been characterized by spectroscopic methods and single crystal X-ray diffraction analyses have been completed for 2, 3, 4 and 5. The coordination chemistry of the ligands with Nd(NO₃)₃ and Yb(NO₃)₃ has been examined and structure determinations for [Nd(2)₂(NO₃)₃(CH₃OH)], [Nd(2)₂(NO₃)₃], [Yb(3)₂(NO₃)₃(H₂O)]·0.5(CH₃OH), [Nd(3)₂(NO₃)₃]·3(CHCl₃), [Nd(4)₂(NO₃)₃(H₂O)], [Yb(4)₂(NO₃)₃(H₂O)] and [Yb(5)₂(NO₃)₃(H₂O)]·0.5(CH₃CN) are reported. Depending upon conditions, the ligands act as monodentate PO or bidentate, chelating PO,N donors.     

Preparation and configurational stability of chiral chloro-[D1]methyllithiums of 98% enantiomeric excess

Enantiopure stannyl-[D1]methanol was converted to chloro-[D1]methylstannane under complete inversion of configuration using Ph3P/N-chlorosuccinimide in THF. It was transmetalated to stereospecifically give chloro-[D1]methyllithium (ee up to 98%). Its microscopic configurational stability was tested by performing tin-lithium exchange in the presence of benzaldehyde as the electrophile under various conditions. The macroscopic configurational stability was addressed by using the same electrophile but by adding it 30 s after the addition of MeLi used for transmetalation. Chloro-[D1]methyllithium is chemically very labile, however completely configurationally stable on both time scales up to the temperature of rapid decomposition (-78 degrees C).     

The synthesis of ethyl 2-[(2,2-dibenzoyl)ethenyl]amino-3-dimethyl-aminopropenoate and its application to the synthesis of fused 3-aminopyran-2-ones and 3-aminoazolo- and -azinopyrimidin-4(4H)-ones

Ethyl 2-[(2,2-dibenzoyl)ethenyl]amino-3-dimethylaminopropenoate ( 3 ) was prepared from dibenzoylmethane ( 1 ) in two steps, and used as a reagent for preparation of fused substituted 3-aminopyranones 12–15 in over 90% yield, quinolizin-4-one 16 in over 79% yield, and fused pyrimidin-4-ones 17–19 in 40–50% yield. Deprotection of (2,2-dibenzoyl)ethenyl group with either diethylamine or hydrazine hydrate produced free amino compounds 20, 21 and 22 in 35%, 91% and 71% yield, respectively.     

Isopropylammonium Layered Uranyl Chromates: Syntheses and Crystal Structures of [(CH3)2CHNH3]3[(UO2)3(CrO4)2O(OH)3] and[(CH3)2CHNH3]2[(UO2)2(CrO4)3(H2O)]

Two novel isopropylamine‐templated uranyl chromates, [(CH₃)₂CHNH₃]₃[(UO₂)₃(CrO₄)₂O(OH)₃] ( 1 ) and [(CH₃)₂CHNH₃]₂[(UO₂)₂(CrO₄)₃(H₂O)] ( 2 ) were prepared by hydrothermal method at 100 °C. The compounds were characterized by electron microprobe analysis and X‐ray diffraction crystal structure analysis [ 1 : trigonal, P31m, a = 9.646(4), c = 8.469(4) Å, V = 682.4(5) ų; 2 : monoclinic, P2₁/c, a = 11.309(3), b = 11.465(3), c = 17.055(5) Å, β = 99.150(6)°, V = 2183.2(11) ų]. The structure of 1 is based upon trimers of uranyl bipyramids interlinked by CrO₄ tetrahedra to form [(UO₂)₃(CrO₄)₂O(OH)₃]^3– layers, whereas, in the structure of 2 , UO₇ and UO₆(H₂O) pentagonal bipyramids are linked through CrO₄ tetrahedra into the [(UO₂)₂(CrO₄)₃(H₂O)]^2– layers. The structures show many similarities to related uranyl selenate compounds, thus providing additional data on similarities and differences between uranyl sulfates, chromates, selenates, and molybdates.     

Synthesis and properties of 1-[(adamantan-1-yl)methyl]-3-pyrazolyl ureas

Chemistry of Heterocyclic Compounds - A series of 1,3-disubstituted ureas containing 1,3,5-trisubstituted pyrazole and (adamantan-1-yl)methyl fragments were synthesized in the reaction of...