Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Access to 3,3-disubstituted oxindoles via microwave-assisted Cannizzaro and aldol reactions of formaldehyde with isatins and their imines.

ABSTRACT: 3,3-Disubstituted oxindoles are important structure motifs in natural products and pharmaceutical agents. Here we disclose a simple and direct access to this class of molecules by using readily available formaldehyde and isatins (and their imines) as the substrates. The reaction proceeds with the assistance of microwave heating in the presence of a mild base. Formaldehyde behaves as both a reductant (via a Cannizzaro process with isatin) and an electrophile.

SUBMITTER: Huang X

PROVIDER: S-EPMC9033177 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Access to 3,3-disubstituted oxindoles via microwave-assisted Cannizzaro and aldol reactions of formaldehyde with isatins and their imines.

Huang Xuan X Wang Hongling H Cao Qingxiang Q Li Yong Y Zhang Junmin J

RSC advances 20210511 28

3,3-Disubstituted oxindoles are important structure motifs in natural products and pharmaceutical agents. Here we disclose a simple and direct access to this class of molecules by using readily available formaldehyde and isatins (and their imines) as the substrates. The reaction proceeds with the assistance of microwave heating in the presence of a mild base. Formaldehyde behaves as both a reductant (via a Cannizzaro process with isatin) and an electrophile. ...[more]

PMID: 35479673

Similar Datasets

A versatile synthesis of unsymmetrical 3,3'-bioxindoles: stereoselective Mukaiyama aldol reactions of 2-siloxyindoles with isatins.

Project description:A new synthesis of 3,3'-bioxindoles is reported that is well suited for the preparation of unsymmetrical structures. In the key step, 3-hydroxy-3,3'-bioxindoles are constructed by Mukaiyama aldol reaction of 2-siloxyindoles with isatins. These tertiary carbinols are formed in high diastereoselectivities, with substitution at various positions of the isatin and the 2-siloxyindole being tolerated.

| S-EPMC2634855 | biostudies-literature

Ascorbic Acid-Initiated Tandem Radical Cyclization of N-Arylacrylamides to Give 3,3-Disubstituted Oxindoles.

Project description:An ascorbic acid-promoted and metal-free tandem room temperature cyclization of N-arylacrylamides with 4-nitrobenzenediazonium generated in situ was developed. This reaction proceeds smoothly through a radical mechanism and provides an environmentally friendly alternative approach to biologically active 3-alkyl-3-benzyloxindoles, avoiding the use of excess oxidants and light irradiation.

| S-EPMC6332015 | biostudies-literature

Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines.

Project description:2-Substituted indoles may be directly transformed to 3,3-dialkyl indolenines with trichloroacetimidate electrophiles and the Lewis acid TMSOTf. These reactions provide rapid access to complex indolenines which are present in a variety of complex natural products and medicinally relevant small molecule structures. This method provides an alternative to the use of transition metal catalysis. The indolenines are readily transformed into spiroindoline systems which are privileged scaffolds in medicinal chemistry.

| S-EPMC6891773 | biostudies-literature

Catalytic stereoselective synthesis of diverse oxindoles and spirooxindoles from isatins.

Project description:A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles.

| S-EPMC4795923 | biostudies-literature

Synthesis and Evaluation of N-Diaminophosphoryl Aminothioureas as Bifunctional Catalysts for Vinylogous Aldol Reactions of Isatins and 2(3H)-Furanones

Project description:The organocatalytic asymmetric direct vinylogous aldol reaction of N-methylisatins 1 and γ-butenolides 2 to provide 3-hydroxy-2-oxindole derivatives 3 was investigated.

| S-EPMC9878653 | biostudies-literature

Synthesis of 3,3-Disubstituted Thietane Dioxides.

Project description:4-Membered heterocycles have been increasingly exploited in medicinal chemistry and, as small polar motifs, often show important influence on activity and physicochemical properties. Thietane dioxides similarly offer potential in both agricultural and pharmaceutical applications but are notably understudied. Here we report a divergent approach to 3,3-disubstituted thietane dioxide derivatives by forming carbocations on the 4-membered ring with catalytic Lewis or Brønsted acids. Benzylic tertiary alcohols of the thietane dioxides are coupled directly with arenes, thiols, and alcohols.

| S-EPMC11536365 | biostudies-literature

Organocatalysed one-pot three component synthesis of 3,3'-disubstituted oxindoles featuring an all-carbon quaternary center and spiro[2H-pyran-3,4'-indoline].

Project description:A simple and efficient methodology for the one-pot synthesis of 3,3'-disubstituted oxindoles featuring an all-carbon quaternary center has been demonstrated through l-proline catalysed three-component reaction based on sequential Knoevenagel condensation/Michael addition and also one-pot synthesis of spiro[2H-pyran-3,4'-indoline] through consecutive Knoevenagel condensation/Michael addition/reduction/cyclization reactions from readily available isatin derivatives, malononitrile, and ketones. The present methodology presents several advantages, including simple reaction set-up, short reaction times, and easy to work-up. Also, this strategy offers broad substrate scope with excellent yields and high atom economy, under mild reaction conditions.

| S-EPMC10140734 | biostudies-literature

Enantioselective reductive multicomponent coupling reactions between isatins and aldehydes.

Project description:A metal-free stereoselective reductive coupling reaction between isatins and aldehydes is reported. The reaction relies on commercial diethyl phosphite (∼€70 kg-1) as the stoichiometric reductant. Base-catalyzed Pudovik addition and phosphonate/phosphate rearrangement achieved polarity inversion on the isatin, and the derived carbanions were trapped by aldehydes with subsequent dialkoxyphosphinyl migration. Chiral iminophosphoranes were used as basic catalysts to achieve high diastereo- and enantioselectivities with excellent yields.

| S-EPMC4618493 | biostudies-literature

Asymmetric vinylogous aldol addition of alkylidene oxindoles on trifluoromethyl-α,β-unsaturated ketones.

Project description:A novel vinylogous aldol addition of alkylidene oxindole with 1-trifluoromethyl-3-alkylidene-propan-2-ones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of oxindoles for the preparation of enantioenriched trifluoromethylated allylic alcohols.

| S-EPMC9086480 | biostudies-literature

Catalytic asymmetric umpolung reactions of imines.

Project description:The carbon-nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon-carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon-carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.

| S-EPMC4513368 | biostudies-literature