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Continuous flow synthesis of indoles by Pd-catalyzed deoxygenation of 2-nitrostilbenes with carbon monoxide

The palladium-catalyzed deoxygenation of o-vinylnitrobenzenes employing carbon monoxide as a terminal reductant produces indoles in a continuous flow environment. The reaction proceeds with catalyst loadings of 1 to 2 mol% Pd(OAc)2 in the presence of suitable ligands/additives and generates carbon dioxide as the only stoichiometric side-product. The reductive cyclization proceeds in a clean fashion with high initial reaction rates in the pressurized flow reactor, ultimately leading to deposition of catalytically inactive palladium(0) inside the channels of the flow device, allowing for an efficient catalyst recovery. A variety of o-vinylnitrobenzenes (o-nitrostilbenes and -styrenes) were converted to the corresponding indoles within 15 to 30 min at a reaction temperature of 140 C to furnish products in good to excellent yields (10-20 bar CO pressure). Mechanistic aspects and the scope of the transformation are discussed.

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Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based on transfer hydrogenation to imines

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.

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Commercial Supported Gold Nanoparticles Catalyzed Alkyne Hydroamination and Indole Synthesis

Commercial gold nanoparticles supported on titanium dioxide (TiO2) were found to be a highly efficient catalyst for alkyne hydroamination. Terminal alkynes could easily undergo intermolecular hydroamination with low catalyst loadings (0.2 mol% Au) under solvent-free conditions. Indoles were efficiently synthesized using microwave heating through intramolecular hydroamination. (Figure presented.).

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Inhibition of cytosolic phospholipase A2alpha: Hit to lead optimization

Compound 1 was previously reported to be a potent inhibitor of cPLA 2alpha in both artificial monomeric substrate and cell-based assays. However, 1 was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC50 of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzole acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma- linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA2alpha inhibition. The IC50s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA2alpha and represent well-validated starting points for further optimization.

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Ionic Liquid Promoted Diazenylation of N-Heterocyclic Compounds with Aryltriazenes under Mild Conditions

An efficient, mild, and metal-free approach to direct diazenylation of N-heterocyclic compounds with aryltriazenes using Br°nsted ionic liquid as a promoter has been developed for the first time. Many N-heterocyclic azo compounds were synthesized in good to excellent yields at room temperature under an open atmosphere. Notably, the promoter 1,3-bis(4-sulfobutyl)-1H-imidazol-3-ium hydrogen sulfate could be conveniently recycled and reused with the same efficacies for at least four cycles.

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A Mild Approach for the Synthesis of Indoles from N -(2-Iodo-aryl)formAamides and Phenylacetylene by a Copper(I)- and Palladium-Catalyzed Cascade Process

An efficient one-pot copper(I)- and palladium-catalyzed synthesis of indoles from N-(2-iodo-aryl)formamides and phenylAacetylene is described. The cascade reaction comprises a Sonogashira cross-coupling, an intramolecular C-N bond formation, and hydrolysis of the intermediate indole-1-carbaldehyde promoted by the same catalyst and base systems.

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Electrosynthesis of substituted 1H-indoles from o-nitrostyrenes

A novel procedure has been devised for the synthesis of derivatives of 1H-indole that is based on the direct, room-temperature electrochemical reduction of substituted o-nitrostyrenes at carbon cathodes in N,N-dimethylformamide containing tetramethylammonium tetrafluoroborate as supporting electrolyte and in the presence of a 10-fold molar excess of a proton donor (phenol or methyl 3-oxobutanoate).

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Microwave-assisted synthesis of indole-derivatives via cycloisomerization of 2-alkynylanilines in water without added catalysts, acids, or bases

An unprecedented green methodology is described for the preparation of differently substituted indoles via microwave-assisted cycloisomerization of 2-alkynylaniline derivatives in water. Moderate to good yields in the cyclization can be achieved for a variety of 2-aminoaryl alkynes. Reactions are run without any added metal catalyst, acid, or base, and do not take place by applying conventional heating.

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PtCl2-catalyzed reactions of o-alkynylanilines with ethyl propiolate and dimethyl acetylenedicarboxylate

The PtCl2-catalyzed reactions between indoles and ethyl propiolate gave rise to mono and double addition products. The composition of the products was largely influenced by the substituents on the indoles as well as the amount of ethyl propiolate used. o-Alkynylanilines reacted with ethyl propiolate and dimethyl acetylenedicarboxylate under the catalysis of PtCl2 to generate the corresponding 2,3-disubstituted indoles. The reaction proceeded by following a sequential cyclization/intermolecular addition pathway.

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Regio-selective synthesis of diversely substituted benzo[a]carbazoles through Rh(iii)-catalyzed annulation of 2-arylindoles with alpha-diazo carbonyl compounds

A novel synthetic approach toward benzo[a]carbazoles or 6-amino benzo[a]carbazoles containing an unprotected NH unit through Rh(iii)-catalyzed cascade reactions of 2-arylindoles or 2-arylindole-3-carbonitriles with alpha-diazo carbonyl compounds has been established. To our knowledge, this is the first example in which the NH unit of indole is used as a directing group for an intramolecular C(sp2)-H bond functionalization to give benzo[a]carbazole derivatives. Notably, this method features easily obtainable substrates, good functional group tolerance, excellent regio-selectivity, and high atom-efficiency.

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