thiourea and 2-oxindole

A highly efficient phospha-aldol reaction for the synthesis of α

Topics: Aldehydes; Catalysis; Indoles; Isatin; Organophosphonates; Oxindoles; Phosphines; Thiourea

We synthesized a series of novel 5-24 derivatives of oxindole. The synthesis started from 5-chlorooxindole, which was condensed with methyl 4-carboxybezoate and result in the formation of benzolyester derivatives of oxindole which was then treated with hydrazine hydrate. The oxindole benzoylhydrazide was treated with aryl acetophenones and aldehydes to get target compounds 5-24. The synthesized compounds were evaluated for urease inhibition; the compound 5 (IC50 = 13.00 ± 0.35 μM) and 11 (IC50 = 19.20 ± 0.50 μM) showed potent activity as compared to the standard drug thiourea (IC50 = 21.00 ± 0.01 μM). Other compounds showed moderate to weak activity. All synthetic compounds were characterized by different spectroscopic techniques including (1)H NMR, (13)C NMR, IR and EI MS. The molecular interactions of the active compounds within the binding site of urease enzyme were studied through molecular docking simulations.

Topics: Benzamides; Enzyme Activation; Hydrazines; Hydrogen Bonding; Indoles; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Molecular Structure; Oxindoles; Urease

A new Michael-Michael cascade reaction between 2-(2-oxoindolin-3-ylidene)acetic esters 1 and nitroenoates 2, catalyzed by bifunctional thioureas, is investigated. The combination of the two Michael reactions results in a novel and facile [4+2] or [3+2] spiroannulation process, which is characterized by the following features: 1) two carbon-carbon bonds and four stereocenters, including a quaternary spiro carbon, are formed under mild conditions; 2) an unprecedented and stereochemically defined substitution pattern on the spirocarbocyclic unit is obtained; 3) the double-bond configuration of the donor-acceptor nitroenoate 2 determines the absolute configuration of the spiro center, whereas the remaining stereocenters are formed under control of the catalyst. The effect on the final stereochemical outcome of structural variations of each starting material, catalyst, and experimental conditions is analyzed in detail. In particular, the use of specifically designed chiral nitroenoates enables diverse polyfunctional spirocyclohexane derivatives containing six consecutive stereogenic centers to be constructed. To our knowledge, this is the first asymmetric organocatalytic strategy enabling both five- and six-membered β-nitro spirocarbocyclic oxindoles.

Topics: Catalysis; Indoles; Nitro Compounds; Oxindoles; Spiro Compounds; Stereoisomerism; Thiourea

A cascade aldol-cyclization reaction between 3-isothiocyanato oxindoles and α-ketophosphonates has been developed for the synthesis of β-amino-α-hydroxyphosphonate derivatives. Catalyzed by a quinine-based tertiary amino-thiourea derivative, this reaction delivers 2-thioxooxazolidinyl phosphonates based on a spirooxindole scaffold bearing two contiguous quaternary stereogenic centers in high yields with excellent diastereo- (up to >20:1 dr) and enantioselectivities (up to >99:1 er).

Topics: Aldehydes; Catalysis; Cyclization; Indoles; Isothiocyanates; Molecular Structure; Organophosphonates; Oxindoles; Quinine; Spiro Compounds; Stereoisomerism; Thiourea

Chiral aza-ortho-xylylene intermediates were efficiently generated from 3-chloro-3-substituted oxindole precursors. The first intramolecular trapping of chiral aza-ortho-xylylene intermediates led to a highly asymmetric synthesis of 3-spirocyclopropyl-2-oxindoles.

Topics: Alkenes; Amines; Aza Compounds; Catalysis; Indoles; Oxindoles; Stereoisomerism; Thiourea

Anything between ureas? Spiro[isoxazolidine-3,3'-oxindole]s have been constructed by employing methyleneindolinones and nitrones as the starting materials through [3+2] annulation catalyzed by a bisthiourea. Products with three contiguous stereocenters, including one spiroquaternary stereocenter, are obtained in good yields with excellent enantio- and diastereoselectivity. The bisthiourea catalyst acts as a multiple-hydrogen-bond donor to simultaneously activate both substrates.

Topics: Catalysis; Cyclization; Hydrogen Bonding; Indoles; Molecular Structure; Oxindoles; Spiro Compounds; Stereoisomerism; Thiourea

Chiral bifunctional tertiary amine thiourea was applied to catalyze the asymmetric hydroxyamination of 3-subsituted oxindoles with nitrosobenzene to construct 3-amino-2-oxindoles with quaternary stereocenters in good yields (up to 91%) and enantioselectivities (up to 90% ee).

Topics: Amination; Amines; Catalysis; Indoles; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea

An enantioselective α-oxyamination of unprotected 3-substituted oxindoles with nitrosobenzene catalyzed by tertiary amine-thiourea bifunctional organocatalysts has been developed and affords the corresponding 3-amino-2-oxindole derivatives in good yields and with moderate to excellent enantioselectivities (up to > 99.9 : 0.1 er when the product is isolated by direct filtration from the reaction mixture). The absolute configuration of the major enantiomers of the products has been established both by chemical correlation and by comparison between the theoretically calculated and the experimental ECD.

Topics: Amination; Amines; Catalysis; Indoles; Models, Molecular; Molecular Conformation; Oxindoles; Stereoisomerism; Thiourea

Topics: Alkylation; Catalysis; Cinchona Alkaloids; Indoles; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea; Vinyl Compounds

The first highly enantioselective decarboxylative addition of β-ketoacids to isatins mediated by a bifunctional tertiary amine-thiourea catalyst has been developed, allowing facile synthesis of biologically important 3-hydroxy oxindoles in good yields and excellent enantioselectivities. The method reported represents a valuable approach of utilizing β-ketoacids as synthetic equivalents of aryl/alkyl methyl ketone enolates.

Topics: Catalysis; Indoles; Isatin; Keto Acids; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea

Sulfenylated oxindoles: The first asymmetric sulfenylation of N-Boc-protected oxindoles has been developed to provide products containing a tetrasubstituted stereogenic center in high to excellent yields (86-98 %) and, in most cases, excellent enantioselectivities (up to 96 % ee; see scheme).

Topics: Amides; Catalysis; Crystallography, X-Ray; Indoles; Models, Molecular; Molecular Structure; Oxindoles; Pyrrolidines; Thiourea

A highly enantioselective Michael addition of 3-aryloxindole to vinyl bisphosphonate ester catalyzed by a cinchonidine derived thiourea catalyst has been investigated. The corresponding adducts, containing a chiral quaternary carbon center and geminal bisphosphonate ester fragment at the 3-position of the oxindole, were obtained in moderate to good yields (65-92%) and moderate to good enantioselectivities (up to 92% ee).

Topics: Catalysis; Cinchona Alkaloids; Diphosphonates; Esters; Indoles; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea

A highly enantioselective Michael addition of 2-oxindoles (1) to vinyl selenone (2) in RTILs catalyzed by a Cinchona alkaloid-based thiourea has been developed in high yields (80-91%) with excellent enantioselectivities (up to 95% ee).

Topics: Catalysis; Cinchona Alkaloids; Indoles; Ionic Liquids; Oxindoles; Selenium; Stereoisomerism; Temperature; Thiourea; Vinyl Compounds

A highly diastereo- and enantioselective Michael addition reaction with respect to prochiral 3-substituted oxindoles and maleimides by a chiral bifunctional thiourea-tertiary amine catalyst was investigated for the first time. The corresponding adducts, containing a quaternary center at the C3-position of the oxindole as well as a vicinal tertiary center, were generally obtained in good to high yields (up to 92%) with high to excellent diastereo- (up to 99:1 dr) and enantioselectivities (up to 99% ee).

Topics: Amines; Catalysis; Indoles; Maleimides; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea

A bifunctional thiourea-tertiary amine-catalyzed asymmetric hydroxymethylation of 3-substituted oxindoles using paraformaldehyde as the C1 unit was developed. A wide scope of oxindoles, bearing C3 sterically congested quaternary carbon centers, were smoothly obtained in good to excellent yields (up to 99%) and high enantioselectivities (up to 91% ee) under mild reaction conditions. A more significant feature of this approach employs cheap and readily available paraformaldehyde as a hydroxymethylation C1 unit, which is activated by chiral bifunctional thiourea organocatalysts.

Topics: Catalysis; Formaldehyde; Indoles; Methylation; Molecular Structure; Oxindoles; Polymers; Stereoisomerism; Thiourea

Topics: Amino Acids; Carbon; Catalysis; Indoles; Molecular Structure; Oxindoles; Stereoisomerism; Sulfones; Thiourea

Topics: Acrylonitrile; Catalysis; Combinatorial Chemistry Techniques; Hydrocarbons, Chlorinated; Indole Alkaloids; Indoles; Oxindoles; Pyrroles; Stereoisomerism; Thiourea

Oxindoles and their indoline derivatives are common structural motifs found in a wide array of natural and biologically active molecules. Most catalytic methods for the asymmetric syntheses of these compounds rely heavily on the use of transition-metal catalysts. In contrast, alternative catalytic procedures involving organocatalysis are scarce. Herein we disclose a conceptually novel organocatalytic approach to the syntheses of these materials using thiourea-catalyzed asymmetric 1,4-additions of oxindole derivatives to nitroolefins as a key step. These addition reactions create up to two stereogenic centers, one of which is a quaternary center. These reactions are broad in scope with respect to both the oxindole and nitroolefin substrates and provide the desired products in good yields with enantioselectivities of up to 99% and diastereoselectivities of up to >20:1. To demonstrate the utility of this approach, (+)-esermethole was synthesized in good overall yield over 3 steps starting from the 1,4-addition product, thereby providing a formal synthesis of (+)-physostigmine.

Topics: Alkenes; Catalysis; Cholinesterase Inhibitors; Indoles; Molecular Structure; Nitro Compounds; Oxindoles; Physostigmine; Stereoisomerism; Thiourea

The asymmetric Mannich reaction of 3-substituted oxindoles and N-Boc imines was investigated for the first time, employing bifunctional thiourea-tertiary amine organocatalysts based on DPEN scaffold. The novel transformations exhibited high diastereoselectivities, and the Mannich adducts bearing adjacent quaternary and tertiary chiral centers were generally obtained in good to excellent enantioselectivities (up to 95% ee).

Topics: Amines; Catalysis; Crystallography, X-Ray; Hydrogen Bonding; Imines; Indoles; Models, Molecular; Molecular Structure; Oxindoles; Stereoisomerism; Thiourea