Formation Of Oxindoles Research Articles

Rhodium(III)‐Catalysed Carbenoid C(sp2)–H Functionalisation of Aniline Substrates with α‐Diazo Esters: Formation of Oxindoles and Characterisation/Utility of an Intermediate‐Like Rhodacycle

An efficient RhIII‐catalysed reaction of 2‐anilinopyridines with sulfonylated α‐diazo esters under mild conditions gave oxindole derivatives, while an analogous reaction of anilinopyrimidine precursors using α‐diazo esters led to the ortho‐alkylation products. The carbenoid coupling reaction was successfully extended to 6‐anilinopurine/purine nucleosides, and the ortho‐alkylated 6‐anilinopurines could be obtained in excellent yields. Proof of the involvement of an Rh–C‐bonded species comes from the characterisation of an intermediate‐like rhodacycle (which is also an active catalyst) by single‐crystal X‐ray crystallography.

UV light-mediated difunctionalization of alkenes through aroyl radical addition/1,4-/1,2-aryl shift cascade reactions.

UV light-mediated difunctionalization of alkenes through an aroyl radical addition/1,4-/1,2-aryl shift has been described. The resulted aroyl radical from a photocleavage reaction added to acrylamide compounds followed by cyclization led to the formation of oxindoles, whereas the addition to cinnamic amides aroused a unique 1,4-aryl shift reaction. Furthermore, the difunctionalization of alkenes of prop-2-en-1-ols was also achieved through aroyl radical addition and a sequential 1,2-aryl shift cascade reaction.

ChemInform Abstract: A Room Temperature Decarboxylation/C—H Functionalization Cascade by Visible‐Light Photoredox Catalysis.

An elegant approach to quaternary oxindole formation has been developed through a room temperature decarboxylation/radical C–H functionalization by visible-light photoredox catalysis.

A Facile Approach for the Asymmetric Synthesis of Oxindoles with a 3-Sulfenyl-Substituted Quaternary Stereocenter

With the employment of a threonine-incorporating multifunctional catalyst 9, Michael addition of 3-sulfenyloxindoles to nitroolefins proceeded stereoselectively, leading to the formation of oxindoles with a 3-sulfenyl-substituted quaternary center in excellent yields, and with high diastereoselectivities and excellent enantioselectivities.

A room temperature decarboxylation/C–H functionalization cascade by visible-light photoredox catalysis

An elegant approach to quaternary oxindole formation has been developed through a room temperature decarboxylation/radical C-H functionalization by visible-light photoredox catalysis.

Experimental and computational thermochemical study of oxindole

Abstract An experimental and computational thermochemical study was performed for oxindole. The standard ( p ∘ = 0.1 MPa ) molar enthalpy of formation of solid oxindole was derived from the standard molar energy of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The respective standard molar enthalpy of sublimation, at T = 298.15 K, was measured by Calvet microcalorimetry. The standard molar enthalpy of formation in the gas phase was derived as −(66.8 ± 3.2) kJ · mol −1 . Density functional theory calculations with the B3LYP hybrid functional and the 6-31G∗ and 6-311G∗∗ sets have also been performed in order to obtain the most stable conformation of oxindole. A comparison has been made between the structure of oxindole and that of the related two-ring molecules: indoline and 2-indanone and the one-ring molecules: pyrrolidine and 2,3-dihydropyrrole. The G3(MP2)//B3LYP method and appropriate reactions were used to obtain estimates of the standard molar enthalpy of formation of oxindole in the gas phase, at T = 298.15 K. Computationally obtained estimates of the enthalpy of formation of oxindole are in very good agreement with the experimental gas phase value. The aromaticity of oxindole was evaluated through the analysis of the nucleus independent chemical shifts (NICS) obtained from the B3LYP/6-311G∗∗ wave functions.

IBiox[(−)-menthyl]: A Sterically Demanding Chiral NHC Ligand

An exceedingly sterically demanding, rigid, and chiral NHC ligand, IBiox[(-)-menthyl] (1), was prepared and structurally characterized. With a buried volume of approximately 50%, this ligand arguably represents one of the most sterically demanding monodentate ligands. The ability to use aryl chloride substrates in intramolecular palladium-catalyzed alpha-arylations reveals its unique reactivity. Moreover, C(2)-symmetric 1 allows the highly enantioselective formation of oxindoles with up to 99% ee.

Exploring a New, Connective Pummerer Reaction: Formation of Oxindoles by the Reaction of Thiols with Glyoxamides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Exploring a new, connective Pummerer reaction: formation of oxindoles by the reaction of thiols with glyoxamides

The reaction of a range of thiols with mono- and bis-glyoxamides derived from secondary anilines, triggers a new, connective Pummerer cyclisation process and leads to the formation of oxindoles.

Fate of 3,3‘-Diindolylmethane in Cultured MCF-7 Human Breast Cancer Cells

3,3'-Diindolylmethane (DIM) is a major in vivo product of the cancer preventative agent indole-3-carbinol that is found in vegetables of the genus Brassica. Here, we report on the metabolic fate of radiolabeled DIM in MCF-7 cells. DIM was slowly metabolized to several sulfate conjugates of oxidized DIM products that were primarily detected in the medium. The radioactivity detected in cells was predominantly unmodified DIM (81-93%) at all time intervals up to 72 h treatment. Co-treatment of MCF-7 cells with quercetin slowed the rate that oxidized DIM products accumulated in the medium, while indole[3,2-b]carbazole (ICZ) co-treatment accelerated their production. ICZ is an inducer of P450 1A2, while quercetin is a specific inhibitor of this isoform, suggesting that P450 1A2 is primarily responsible for the oxidation of DIM, probably through 2,3-epoxidation similar to 3-methylindole. Sulfate conjugates of oxidized DIM metabolites were cleaved by sulfatase digestion and identified by LC/MS as 3-(1H-indole-3-ylmethyl)-2-oxindole (2-ox-DIM), bis(1H-indol-3-yl)methanol (3-methylenehydroxy-DIM), 3-[hydroxy-(1H-indol-3-yl)-methyl]-1,3-dihydro-2-oxindole (3-methylenehydroxy-2-ox-DIM), and 3-hydroxy-3-(1H-indole-3-ylmethyl)-2-oxindole (3-hydroxy-2-ox-DIM). Derivatives of 2-ox-DIM represented greater than 30% of the radioactivity in the sulfatase-digested medium. Although oxindole formation was the primary metabolic pathway in MCF-7 cells, synthetic 2-ox-DIM was inactive in a 4-ERE-luciferase reporter assay and, therefore, probably not responsible for the estrogenic activity previously observed for DIM. Unmodified DIM rapidly accumulated in the nuclear membranes representing approximately 35-40% of the radioactivity after 0.5-2 h treatment. Uptake of radiolabeled DIM appeared to be a passive partitioning into the nuclear membranes and was not dependent upon the cell cytosol. The nuclear uptake of DIM was not saturable and could not be blocked by pretreatment with unlabeled DIM (100 microM). Further, treatments in serum-free medium increased the uptake of radiolabeled DIM by the MCF-7 cells. These findings show that the uptake of DIM by membranes significantly increases its localized concentration, which may contribute to its biological activities.

Solid phase chemical technologies for combinatorial chemistry.

This article describes the exploration of synthetic methodologies on solid phase for combinatorial chemistry. Examples will cover various cyclisation strategies that include; the intramolecular Heck cyclisation leading to the formation of oxindoles, the radical cyclisation mechanism in the synthesis of furans, and a stereoselective cyclisation to form oxopiperazines.

ChemInform Abstract: Ligand Effects in the Rhodium(II)‐Catalyzed Reactions of α‐ Diazoamides. Oxindole Formation is Promoted by the Use of Rhodium(II) Perfluorocarboxamide Catalysts.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ligand Effects in the Rhodium(II)-Catalyzed Reactions of .alpha.-Diazoamides. Oxindole Formation is Promoted by the Use of Rhodium(II) Perfluorocarboxamide Catalysts

An improved procedure for the preparation of ethyl 2-diazomalonyl chloride was developed which involves the reaction of ethyl diazoacetate with triphosgene. Using this diazo acid chloride, it was possible to prepare a variety of diazoamides from substituted amines. The rhodium(II)-catalyzed decomposition of these diazoamides was studied in order to probe the chemoselectivity of the carbenoid intermediates in intramolecular insertion reactions. Rhodium(II) acetate decomposition of N-benzyl-2-diazo-N-phenylmalonamic acid ethyl ester resulted in intramolecular C-H insertion to give ethyl 1,4-diphenyl-2-oxoazetidine-3-carboxylate. By changing the catalyst ligand to trifluoroacetamide, β-lactam formation was completely suppressed in favor of the aromatic C-H insertion which produces an oxindole as the only detectable product. The competition between aliphatic and aromatic carbon-hydrogen insertion of 2-diazo-N-isobutyl-N-phenylmalonamic acid ethyl ester provides another example of ligand effectiveness in controlling chemoselectivity in dirhodium (II)-catalyzed metal carbene reactions. Thus, treatment of the N-isobutyldiazoanilide with rhodium(II) acetate results in exclusive aliphatic C-H insertion giving 4,4-dimethyl-2-oxo-1-phenylpyrrolidine-3-carboxylic acid ethyl ester, while the perfluorobutyramide ligand promotes oxindole formation by aromatic C-H insertion. Several other rhodium(II)-catalyzed reactions were studied and were studied and were found to be highly catalyst dependent, rhodium (II) perfluorocarboxamides promoting aromatic C-H insertion, and hence oxindole formation, over O-H insertion, cyclization onto adjacent triple bonds, or cyclization to generate 1,3-dipolar intermediates

Selective formation of oxindole- and formylkynurenine-type products from tryptophan and its peptides treated with a superoxide-generating system in the presence of iron(III)-EDTA: a possible involvement with iron-oxygen complex.

The oxygenation of tryptophan and its peptides by the superoxide-generating system hypoxanthine/xanthine oxidase in the presence of iron(III) and ethylenediaminetetraacetic acid (EDTA) has been investigated. The reaction of a tryptophan derivative, N-(tert-butoxycarbonyl)-L-tryptophan, with hypoxanthine/xanthine oxidase/Fe(III)-EDTA mainly resulted in the oxygenation of the pyrrole ring of the indole nucleus. 2-[(tert-Butoxycarbonyl)-amino]-3-(3-oxindolyl)propionic acid and N-(tert-butoxycarbonyl)-N'-formylkynurenine were identified as the major products. Similar oxindole- and formylkynurenine-type products were also obtained from the N-(tert-butoxycarbonyl) derivative of the tryptophan-containing peptides Ile-Trp, Trp-Leu, Gly-Trp-Leu, and Ala-Trp-Ile. In all cases, however, hydroxylation products of the benzene ring of the indole nucleus were scarcely detected, leading to the assumption that free hydroxyl radical did not play a role in the tryptophan oxidation of this system. Of interest was the fact that the reaction of N-(tert-butoxycarbonyl)-L-tryptophan with H2O2/horseradish peroxidase mainly afforded the same oxindole- and formylkynurenine-type products as those obtained in the hypoxanthine/xanthine oxidase/Fe(III)-EDTA system. Taken together, iron-oxygen complex-type active species may play a role in the tryptophan oxygenation in a superoxide-generating system in the presence of iron-EDTA.

Intramolecular addition of aryl radicals to vinylogous urethanes: studies toward preparation of the oxindole portion of gelsemine

Free radical cyclization of vinylogous urethanes 5 and 12 gave spiro oxindoles 6 and 13 + 14, in 95% and 84% yields, respectively. Cyclization of projected gelsemine intermediate 19 resulted in the formation of oxindole 22 via a cyclization, 1,4-hydrogen atom transfer, reduction sequence.

ChemInform Abstract: Studies on the Formation of Oxindoles from Their Indoloazabicyclo‐(3.3.1)nonane Counterparts and Implications for the Biogenesis of Alstonisine.

AbstractTreatment of the fused azabicyclononane (I) with tert‐butyl hypochlorite and subsequent acidic hydrolysis give the oxindole (II).

Fluoro-contaiming heterocumulenes

A stydy was made of the reaction of oxygen transfer from nitrones to N-aryl-bis(trifluoromethyl)-ketenimines, which leads to the formation of oxindoles.

Mechanism of corn indole-3-acetic acid oxidase in vitro

When indole-3-acetic acid (IAA) was oxidized in the presence of Mn2+ and 2,4-dichlorophenol by a crude corn extract shown to contain IAA oxidase and by non-enzymic oxidation with Mn3+, 10 products of the reaction could be extracted by CH2Cl2 and separated by TLC. Four of these products, 3-hydroxy-methyloxindole, 3-methyleneoxindole, indole-3-aldehyde, and the 3-indolylmethyl ester of indole-3-acetic acid had been previously identified as reaction products. In addition, 3,3′-di-indolylmethane and 3-methyleneindolenine were found. 3-Methyleneindolenine was readily and reversibly formed from 3-hydroxymethylindole. A reaction pathway involving a two-electron oxidation catalyzed by Mn3+ and 3-hydroperoxymethylindole as a key intermediate in oxindole formation is proposed.