Showing papers in "Journal of Organic Chemistry in 2004"

Electron-transfer reaction of cinnamic acids and their methyl esters with the DPPH(*) radical in alcoholic solutions.

Abstract: The kinetic behavior of cinnamic acids, their methyl esters, and two catechols 1−10 (ArOH) in the reaction with DPPH• in methanol and ethanol is not compatible with a reaction mechanism that involv...

Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles.

Abstract: This paper details the copper-catalyzed N-arylation of π-excessive nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides with common nitrogen heterocycles (pyrroles, pyrazoles, indazoles, imidazoles, and triazoles) was successfully performed in good yield with catalysts derived from diamine ligands and CuI. General conditions were found that tolerate functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle. Hindered aryl halides or heterocycles were also found to be suitable substrates using the conditions reported herein.

Asymmetric allylic alkylation, an enabling methodology.

Abstract: The diversity of mechanisms for enantiodiscrimination and of bond types that can be formed make Pd-catalyzed asymmetric allylic alkylation a powerful key step for simplification of synthetic strategy to complex molecular targets. Using a wide range of different classes of compounds including alkaloids, polyhydrofurans, nucleosides and carbanucleosides, cyclohexitols and cyclopentitols, chromanes, cyclopentanoids, amino acids, barbiturates, etc., novel synthetic strategies emerge that provide short efficient asymmetric syntheses.

Perspective on Fluorocarbon Chemistry

Abstract: Fluorocarbons, organic molecules with carbon skeletons and fluorine "skins", differ fundamentally from their hydrocarbon counterparts in interesting and useful ways. A selection of the myriad applications fluorocarbons and their derivatives have found in modern life is described and related to molecular properties. Salient aspects of the nature and reactivity of fluorocarbon compounds are highlighted by comparison with their more familiar hydrocarbon analogues.

Abnormal solvent effects on hydrogen atom abstraction. 2. Resolution of the curcumin antioxidant controversy. The role of sequential proton loss electron transfer.

Abstract: The rates of reaction of 1,1-diphenyl-2-picrylhydrazyl (dpph•) radicals with curcumin (CU, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), dehydrozingerone (DHZ, “half-curcumin”), and isoeugenol (IE) have been measured in methanol and ethanol and in two non-hydroxylic solvents, dioxane and ethyl acetate, which have about the same hydrogen-bond-accepting abilities as the alcohols. The reactions of all three substrates are orders of magnitude faster in the alcohols, but these high rates can be suppressed to values essentially equal to those in the two non-hydroxylic solvents by the addition of acetic acid. The fast reactions in alcohols are attributed to the reaction of dpph• with the CU, DHZ, and IE anions (see J. Org. Chem. 2003, 68, 3433), a process which we herein name sequential proton loss electron transfer (SPLET). The most acidic group in CU is the central keto−enol moiety. Following CU's ionization to a monoanion, ET from the [−(O)CCHC(O)−]- moiety to dpph• yields the neutral [−(O)CCH...

An effective use of benzoic anhydride and its derivatives for the synthesis of carboxylic esters and lactones: A powerful and convenient mixed anhydride method promoted by basic catalysts

Abstract: Various carboxylic esters are obtained at room temperature in excellent yields with high chemoselectivities from nearly equimolar amounts of carboxylic acids and alcohols using 2-methyl-6-nitrobenzoic anhydride with triethylamine by the promotion of a basic catalyst such as 4-(dimethylamino)pyridine. A variety of lactones are also prepared in high yields at room temperature from the corresponding ω-hydroxycarboxylic acids with use of 2-methyl-6-nitrobenzoic anhydride in the presence of 4-(dimethylamino)pyridine. A similar reaction occurs with triethylamine when using a catalytic amount of 4-(dimethylamino)pyridine 1-oxide as an effective promoter for the intramolecular condensation reaction. These methods are successfully applied to the synthesis of erythro-aleuritic acid lactone and an eight-membered-ring lactone moiety of octalactins A and B. The efficiency of the cyclizations is compared to those of other reported lactonizations.

Cross-coupling and dehalogenation reactions catalyzed by (N-heterocyclic carbene)Pd(allyl)Cl complexes.

Abstract: A series of well-defined, air- and moisture-stable (NHC)Pd(allyl)Cl (NHC = N-heterocyclic carbene) complexes has been used in several catalytic reactions: Suzuki−Miyaura cross-coupling, catalytic dehalogenation of aryl halides, and aryl amination. The scope of the three processes using various substrates was examined. A general system involving the use of (IPr)Pd(allyl)Cl as catalyst and NaOtBu as base has proven to be highly active for the Suzuki−Miyaura cross-coupling of activated and unactivated aryl chlorides and bromides, for the catalytic dehalogenation of aryl chlorides, and for the catalytic aryl amination of aryl triflates. All reactions proceed in short reaction times and at mild temperatures. The system has also proven to be compatible with the microwave-assisted Suzuki−Miyaura cross-coupling and catalytic dehalogenation processes, affording yields similar to those of the conventionally heated analogous reactions.

Preparation and Characterization of Regioisomerically Pure 1,7-Disubstituted Perylene Bisimide Dyes

Abstract: A detailed study on bromination and subsequent imidization of perylene bisanhydride with cyclohexylamine is reported. The present results reveal that previously reported 1,7-difunctionalized perylene bisimides are presumably contaminated with the respective 1,6 regioisomers. N,N'-Dicyclohexyl-1,7-dibromoperylene bisimide 1,7-3 is obtained for the first time in isomerically pure form, and its structure is unequivocally confirmed by X-ray analysis. By using regioisomerically pure 1,7-dibromoperylene bisimide 1,7-3, 1,7-dipyrrolidinylperylene bisimides 4a-c and 1,7-dipyrrolidinylperylene bisanhydride 5 as well as the unsymmetrically difunctionalized 1-bromo-7-pyrrolidinyl- and 1-cyano-7-pyrrolidinylperylene bisimides 7 and 8 are synthesized in good yield.

Efficient functionalization of aromatic C-H bonds catalyzed by gold(III) under mild and solvent-free conditions.

Abstract: A gold(III)-catalyzed carbon−carbon bond formation reaction between arenes and electron-deficient alkynes or alkenes is described. Electron-rich arenes can be efficiently functionalized with the alkyne or alkene substrates. This reaction can be run with neat reactants at ambient temperature. Under the “solventless” conditions, clean product was obtained from a reaction of equal molar amounts of arene and alkyne substrates. The mild conditions and potential tolerance to different functional groups make this method practical for arene functionalization and for constructing complicated molecules. Efficient preparation of various coumarins from aryl alkynoates was demonstrated. Preliminary mechanistic studies were performed to probe the pathway of this reaction.

Selective Iron-Catalyzed Cross-Coupling Reactions of Grignard Reagents with Enol Triflates, Acid Chlorides, and Dichloroarenes

Abstract: Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)3 are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C−C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron−ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)2]n generated in situ. Control experiments using the ate-complex [Me4Fe]Li2 corroborate this inter...

TBAF-catalyzed synthesis of 5-substituted 1H-tetrazoles under solventless conditions.

Abstract: Tetrabutylammonium fluoride (TBAF) is an efficient catalyst in the [3 + 2] cycloaddition reaction of organic nitriles 1 with trimethylsilyl azide (TMSN(3)) in solventless conditions. The corresponding 5-substituted 1H-tetrazoles 2 were obtained under mild conditions and in 80-97% yields.

Aqueous-phase, palladium-catalyzed cross-coupling of aryl bromides under mild conditions, using water-soluble, sterically demanding alkylphosphines.

Abstract: Sterically demanding, water-soluble alkylphosphines have been used in combination with various palladium salts in Suzuki, Sonogashira, and Heck couplings of aryl bromides under mild conditions in aqueous solvents. The tert-butyl-substituted ligands 2-(di-tert-butylphosphino)ethyltrimethylammonium chloride (t-Bu-Amphos) and 4-(di-tert-butylphosphino)-N,N-dimethylpiperidinium chloride (t-Bu-Pip-phos) in combination with palladium(II) salts were found to give catalysts that were significantly more active than catalysts derived from tri(3-sulfonatophenyl)phosphine trisodium (TPPTS). Suzuki couplings of unactivated aryl bromides occurred efficiently at room temperature in water/acetonitrile and water/toluene biphasic mixtures or in neat water. Notably, Suzuki couplings of hydrophilic aryl bromides gave high yields without using organic solvents for the reaction or purification. This methodology has been applied to a highly efficient synthesis of diflunisal. The catalyst derived from t-Bu-Amphos was recycled th...

New Hg2+-selective chromo- and fluoroionophore based upon 8-hydroxyquinoline.

Abstract: A new 8-hydroxyquinoline derivative having an appended boron−dipyrromethene function has been prepared, and its metal ion sensing properties were investigated. The designed compound exhibited pronounced Hg2+-selective on−off-type fluoroionophoric properties among the representative transition- and heavy-metal ions in aqueous dioxane solution. The fluorescence was efficiently quenched more than 98% with 5 equiv of Hg2+ ions, and the detection limit was found to be 5 × 10-6 M in a dioxane−water (1:3, v/v) solvent system. The ionophore also showed a selective chromogenic behavior toward Hg2+ ions by changing the color of the solution from light amber to red, which can be detected with the naked eye.

Development of an Efficient Procedure for Indole Ring Synthesis from 2-Ethynylaniline Derivatives Catalyzed by Cu(II) Salts and Its Application to Natural Product Synthesis

Abstract: The development of efficient methods for the indole synthesis catalyzed by Cu(II) salts and its applications were investigated. Cu(OAc)2 has been proved to be the best catalyst for the synthesis of various 1-p-tolylsulfonyl or 1-methylsulfonylindoles, which have both electron-withdrawing and electron-donating groups on the aromatic ring and C2 position of indoles. For the primary aniline derivatives, Cu(OCOCF3)2 showed good activities, while Cu(OAc)2 was a good catalyst for the cyclization of secondary anilines. This methodology could be applied to the sequential cyclization reaction for the compounds which have the electrophilic part in the same molecule. By prior treatment with KH, the sequential cyclization was realized to provide the tricyclic ring systems, but it was limited to five- and six-membered rings for the second cyclization. Finally, formal and total synthesis of hippadine with the Cu(II)-promoted indole synthesis as the key step was accomplished.

Magnesium-induced copper-catalyzed synthesis of unsymmetrical diaryl chalcogenide compounds from aryl iodide via cleavage of the Se-Se or S-S bond.

Abstract: The methodology for a copper-catalyzed preparation of diaryl chalcogenide compounds from aryl iodides and diphenyl dichalcogenide molecules is reported. Unsymmetrical diaryl sulfide or diaryl selenide can be synthesized from aryl iodide and PhYYPh (Y = S, Se) with a copper catalyst (CuI or Cu2O) and magnesium metal in one pot. This reaction can be carried out under neutral conditions according to an addition of magnesium metal as the reductive reagent. Furthermore, it is efficiently available for two monophenylchalcogenide groups generated from diphenyl dichalcogenide.

Simple Synthesis of Substituted Pyrroles

Abstract: Simple synthesis of substituted pyrroles using iodine-catalyzed and montmorillonite KSF-clay-induced modified Paal-Knorr methods has been accomplished with excellent yields. N-Substituted carbazole has also been prepared by following this method. If one of the reactants is a liquid, the reaction proceeds exceedingly well without a solvent. This method gives pyrroles with less nucleophilic multicyclic aromatic amines at room temperature.

Activation of Carbon Dioxide by Bicyclic Amidines

Abstract: Activation of the carbon dioxide molecule was achieved using bicyclic amidines (DBU, PMDBD, and DBN). The solution reaction of CO2 with amidines yielded the corresponding zwitterionic complexes through the formation of a N−CO2 bond. 13C NMR data confirmed the carbamic nature of the carbamic zwitterions, DBU−CO2 and PMDBD−CO2. However, when these adducts were crystallized, the X-ray analyses of the single crystals were in agreement with bisamidinium bicarbonate salt structures, indicating that structural changes occurred in the crystallization process. The elemental and thermogravimetric analysis data for the carbamic zwitterions, DBU−CO2 and PMDBD−CO2, initially obtained by the direct reaction of amidines with CO2, suggest that these molecules are probably associated with one molecule of water by hydrogen-bond formation (amidinium+−COO-···H2O). A correlation was observed between the thermal stability and the transcarboxylating activity for the amidine−CO2 complexes. Theoretical calculations of hardness we...

NiCl2(dppe)-Catalyzed Cross-Coupling of Aryl Mesylates, Arenesulfonates, and Halides with Arylboronic Acids

Abstract: An investigation of the NiCl2(dppe)-, NiCl2(dppb)-, NiCl2(dppf)-, NiCl2(PCy3)2-, and NiCl2(PPh3)2-catalyzed cross-coupling of the previously unreported aryl mesylates, and of aryl arenesulfonates, chlorides, bromides, and iodides containing electron-withdrawing and electron-donating substituents with aryl boronic acids, in the absence of a reducing agent, is reported. NiCl2(dppe) was the only catalyst that exhibited high and solvent-independent activity in the two solvents investigated, toluene and dioxane. NiCl2(dppe) with an excess of dppe, NiCl2(dppe)/dppe, was reactive in the cross-coupling of electron-poor aryl mesylates, tosylates, chlorides, bromides, and iodides. This catalyst was also efficient in the cross-coupling of aryl bromides and iodides containing electron-donating substituents. Most surprisingly, the replacement of the excess dppe from NiCl2(dppe)/dppe with excess PPh3 generated NiCl2(dppe)/PPh3, which was found to be reactive for the cross-coupling of both electron-rich and electron-poo...

Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines.

Abstract: A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90−100 °C in DME as the solvent in the presence of PdI2 in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO2 (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from α-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor.

Oxime carbapalladacycle covalently anchored to high surface area inorganic supports or polymers as heterogeneous green catalysts for the Suzuki reaction in water.

Abstract: An oxime carbapalladacycle known as an extremely active homogeneous catalyst for the Suzuki coupling in water has been conveniently modified and anchored on high surface area SiO2, MCM-41, and polystyrene-divinylbenzene and ethylenglycol dimethylacrylate polymers. The resulting solids were characterized by analytical and spectroscopic (UV−vis and IR) techniques and tested as catalysts for the reaction of 4-chloroacetophenone with phenylboronic acid in water, dioxane, and a mixture of both. Differences in activity depending on the support were remarkable, the palladium complex being more active for the reactions in water when supported on SiO2 or MCM-41. The catalysts were truly heterogeneous (no leached palladium) and when anchored on SiO2 were reused seven times without loosing activity. Palladium complex anchored in SiO2 was also tested as Suzuki catalyst for a wide range of bromo-, chloro-, and even fluoroaromatics.

Salt effects on the apparent stability of the cucurbit[7]uril-methyl viologen inclusion complex.

Abstract: The effects of the medium ionic composition on the apparent equilibrium association constant (K) for the formation of a 1:1 inclusion complex between the guest methyl viologen (MV2+) and the host cucurbit[7]uril (CB7) were studied in aqueous solutions. The K values were found to decrease with increasing ionic strength, with more pronounced effects for solutions containing divalent Ca2+ ions than for solutions containing monovalent Na+ ions. The competing ion−dipole interactions between Ca2+ or Na+ and MV2+ ions appear to be responsible for the remarkable modulation of the K values observed in this work.

Reactions on a solid surface. A simple, economical and efficient Friedel-Crafts acylation reaction over zinc oxide (ZnO) as a new catalyst.

Abstract: Zinc oxide (ZnO) brings about a rapid Friedel-Crafts acylation of a range of activated and unactivated aromatic compounds such as anisole and chlorobenzene with acid chlorides in solvent-free conditions at room temperature. The ZnO powder can be reused up to three times after simple washing with dichloromethane.

Unsymmetrical Diaryl Sulfones and Aryl Vinyl Sulfones through Palladium-Catalyzed Coupling of Aryl and Vinyl Halides or Triflates with Sulfinic Acid Salts

Abstract: The palladium-catalyzed reaction of sulfinic acid salts with a wide variety of aryl and vinyl halides or triflates provides unsymmetrical diaryl sulfones and aryl vinyl sulfones in good to excellent yields. The reaction is strongly influenced by the presence of nBu4NCl, and the use of Xantphos, a rigid bidentate ligand with a wide natural bite angle, was found to be crucial for the success of the reaction. With neutral, electron-rich, and electron-poor aryl iodides best results were obtained by using Pd2(dba)3, Xantphos, Cs2CO3, and nBu4NCl, in toluene at 80 °C. Two general procedures were employed with aryl bromides and triflates: sodium p-toluenesulfinate, Pd2(dba)3, Xantphos, Cs2CO3, 120 °C, in toluene with nBu4NCl (procedure A: neutral, electron-rich, and slightly electron-poor aryl bromides or triflates) and without nBu4NCl (procedure B: electron-poor aryl bromides or triflates). With vinyl triflates best results were obtained at 60 °C omitting nBu4NCl.

Alkyl- or Arylthiolation of Aryl Iodide via Cleavage of the S−S Bond of Disulfide Compound by Nickel Catalyst and Zinc

Abstract: Various aryl sulfides can be synthesized by nickel-catalyzed alkyl- or arylthiolation of aryl iodide with a disulfide compound. This reaction produces Ni(0) from NiBr2−bpy by the reduction with zinc, and this generated complex works as an activating species to convert ArI into ArSR under neutral conditions. Furthermore, this system enables the use of two RS groups in (RS)2.

Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.

Abstract: Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guided fractionation monitored with a human oral epidermoid carcinoma (KB) cell line. Additionally, two new baccharane-type triterpenoids, 17,24-epoxy-25-hydroxybaccharan-3-one (3) and 17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid (4), as well as eleven known compounds, 1β,6α-dihydroxy-4(15)-eudesmene (5), ferulic acid (6), grasshopper ketone (7), apigenin, cabraleone, chrysoeriol, 1β,4β-dihydroxy-6α,15α-epoxyeudesmane, 4-hydroxy-3-methoxyacetophenone, 4-hydroxyphenethyl alcohol, ocotillone, and β-sitosterol 3-O-β-d-glucopyranoside, were also isolated and characterized. The structures of compounds 1−4 were elucidated by spectroscopic studies and by chemical transformation. The absolute stereochemistry of silvestrol (1) was established by a X-ray diffraction study of its di-p-bromobenzoate derivative, and the structure...

Unambiguous detection of target DNAs by excimer-monomer switching molecular beacons.

Abstract: A new class of molecular beacons were developed in which pyrene fluorophores were connected both at 3' and 5' ends of a single-stranded oligonucleotide. The two pyrene-based fluorophores were synthesized from the same starting material, so that the preparation of the beacons was simplified. The detection strategy of the beacons for target DNAs is based on "excimer-monomer emission switching" of the pyrene fluorophores: excimer emission of the pyrene moieties changed to monomer one when the beacons hybridized with the targets. This type of two-state mode of fluorescence allows unambiguous detection of the target DNAs because strict 1:1 correlation between the nonhybridized and the hybridized beacons can be monitored by the presence of isoemissive points of the fluorescence changes. The beacons can detect target 19-mer DNAs and can discriminate the targets from their single-nucleotide mismatches at 1 nM concentration. Advantages of the excimer-monomer switching molecular beacons were discussed in comparison with conventional ones.

Relation between the substituent effect and aromaticity

Abstract: Molecular geometries of benzene and its 18 monosubstituted derivatives were optimized at B3LYP/6-311+G** level of theory. The changes of π-electron delocalization of the benzene fragment were estimated by use of aromatic stabilization energies (ASE) based on different homodesmotic reaction schemes, geometry-based HOMA model, magnetism-based NICS, NICS(1), NICS(1)zz, and an electronic delocalization index, PDI, derived from the AIM theory. Apart from aromatic stabilization energies the other descriptors of aromaticity vary to a very small extent, indicating high resistance of the π-electron structure to the substituent effect. This is somewhat analogous to a tendency of benzene systems to retain their initial π-electron structure during the reaction course that leads to aromatic substitution.

Social Self-Sorting in Aqueous Solution

Abstract: Self-sorting-the ability to efficiently distinguish between self and nonself-is common in nature but is still relatively rare in synthetic supramolecular systems. We report a 12-component mixture comprising 1-11 and KCl that undergoes thermodynamically controlled self-sorting in aqueous solution based on metal-ligand, ion-dipole, electrostatic, charge-transfer interactions, as well as the hydrophobic effect. We refer to this molecular ensemble-characterized by high-fidelity host-guest interactions between components-as a social self-sorting system to distinguish it from narcissistic self-sorting systems based on self-association processes. The influence of several key variables-temperature, pH, concentration, and host/guest stoichiometry-was explored by a combination of simulation and experiment. Variable temperature NMR experiments, for example, revealed a kinetically controlled irreversible process upon cycling from 298 to 338 K, which is an emergent property of this molecular ensemble. Variable pH and concentration experiments, in contrast, did not reveal any emergent properties of the molecular ensemble. Simulations of a four-component mixture establish that by proper control of the relative magnitude of the various equilibrium constants, it is possible to prepare socially self-sorted mixtures that are responsive (irresponsive) to host/guest stoichiometry over narrow (broad) ranges. The 12-component mixture is relatively irresponsive to host/guest stoichiometry. Such social self-sorting systems, like their natural counterparts, have potential applications as chemical sensors, as artificial regulatory elements, and in the preparation of biomimetic systems.

Unique hydrogen bonds between 9-anthracenyl hydrogen and anions.

Abstract: Unique hydrogen bonds of the 9-H of anthracene moieties in hosts 1 and 2 with fluoride and pyrophosphate ions were observed on the basis of the 1H NMR experiments. Furthermore, hosts 1 and 2 act as a colorimetric sensor and a fluorescent chemosensor for the recognition of fluoride ion, respectively.

Highly effective fluorescent sensor for H2PO4(

Abstract: A new anthracene dimer connected by two imidazolium moieties has been systematically designed and synthesized as a fluorescent chemosensor for selective binding of H2PO4- over other anions, which have been examined using fluorescence and 1H NMR and rationalized with ab initio study.