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An organocatalyzed asymmetric dearomative [3+2] annulation reaction of electron‐deficient 2‐nitrobenzo heteroarenes including 2‐nitrobenzofurans, 2‐nitrobenzothiophenes and 2‐nitroindoles with 3‐isothiocyanato oxindoles was developed. With a multiple hydrogen‐bonding bifunctional thiourea as the catalyst, the reaction displays broad substrate scope and provides an access to structurally diverse polycyclic spirooxindoles containing three contiguous stereogenic centers in high yields with good diastereo‐ and enantioselectivities (up to 99% yield, 94:6 dr, and 97% ee). This organocatalysis protocol is able to afford the products with complementarily diastereoselectivity versus the previous work with transition metal catalysis. [ABSTRACT FROM AUTHOR]

We report on the synthesis of the first examples of 1,3-azaborinine derived oxindole systems, the BN-isosteres of the important compound class of the oxindoles. Hydroboration of terminal aryl acetylenes with FmesBH2, followed by treatment with 2 equiv. of a glycine ester derived isonitrile gave a small series of 1,3-azaborinine derived oxindoles. The new BN-oxindoles show interesting photophysical behavior. [ABSTRACT FROM AUTHOR]

An unprecedented palladium-catalyzed asymmetric carbamoyl-carbonylation of tethered alkenes with CO and alcohols has been developed. This reaction provided an efficient route to access oxindoles and γ-lactams bearing β-carbonyl substituted quaternary carbons in good yields with excellent chemo-, regio- and enantioselectivity. Gram-scale synthetic capability and facile transformations of the products to chiral spirooxindole and other functional molecules further illustrated the practicability of this reaction. [ABSTRACT FROM AUTHOR]

We report the development of a rapid approach for directly converting indoles into 2‐oxindoles promoted by HOCl formed in situ from the combination of (bis(trifluoroacetoxy) iodo)benzene (PIFA) and n‐Bu4NCl ⋅ H2O. The procedure is widely functional group tolerant and provides 2‐oxindoles in up to 95% yield within 5 min. The potential applications of the developed methodology are demonstrated by the gram‐scale preparation of 3‐methyl‐2‐oxindole (11 a), the one‐pot two‐step syntheses of spiro‐oxindoles 26 a and 26 b, and the formal synthesis of (‐)‐folicanthine (2). [ABSTRACT FROM AUTHOR]

3,3‐Disubstituted oxindoles bearing quaternary and tertiary stereogenic centers are privileged structural motifs, which widely exist in pharmaceutical and natural products. Herein, a highly regio‐, enantio‐, and diastereoselective allylic alkylation of 3‐alkyl oxindoles through synergistic iridium and copper catalysis is described, which provides a series of 3,3‐disubstituted oxindole derivatives containing adjacent quaternary and tertiary stereogenic centers in excellent yields, enantiomeric excess, and diastereomeric ratio (for 30 examples, up to 97 % yield, >99 % ee, and >20 : 1 dr). This method provides exclusive branched selectivity, excellent enantio‐ and diastereoselectivities, and good functional compatibility. Control experiments suggested that the chiral copper catalyst is required for achieving high reactivities and diastereoselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

An efficient and convergent (4+1)‐cycloaddition strategy toward the construction of spirooxindole benzofurans that involves the intermediacy of an isatin‐derived oxyphosphonium enolate is presented. Mechanistic investigations employing in situ NMR analysis of the reaction mixture revealed a correlation between phosphonium enolate structure and product distribution that was heavily influenced by the solvent and reaction temperature. [ABSTRACT FROM AUTHOR]

Utilizing a palladium‐catalyzed cascade strategy, we have developed an intermolecular aryl‐carbamoylation of unactivated alkenes under mild conditions, allowing for facile access to diverse aryl‐functionalized oxindoles from alkene‐tethered carbamoyl chlorides in moderate to good yields. [ABSTRACT FROM AUTHOR]

A new method was developed for the synthesis of spiro[azepane-4,3′-indol]-2′(1′ H)-ones in yields of up to 96% with a broad substrate scope by using oxotryptamines as dual-nucleophilic reagents to react with allenoates in the presence of cesium carbonate under mild conditions. In accord with previous works and a deprotonation-tracing experiment, a plausible reaction mechanism is proposed. [ABSTRACT FROM AUTHOR]

Carbon bisnucleophiles are important building blocks in organic synthesis and have widespread applications in the construction of carbocyclic compounds. Among them, 1,2‐carbon bisnucleophile has been much less explored. Herein, we developed a [2+3] annulation of 2‐(2‐oxoindolin‐3‐yl)malononitrile with 2‐nitroallylic acetates, where 2‐(2‐oxoindolin‐3‐yl)malononitrile served as a new type of 1,2‐carbon bisnucleophile. Remarkably, the annulation reaction exhibits exclusive chemo‐ and regioselectivity. A Michael addition/SN2 mechanism was proposed to avoid the "anti‐Baldwin" cyclization. This stereoselective strategy provides a facile synthetic route for a new series of spirocyclopentane oxindole derivatives containing three stereogenic centers. [ABSTRACT FROM AUTHOR]

An efficient diastereoselective trans cyclopropanation of 3-alkylidene oxindoles with in situ generated α-diazo carbonyl compounds or α,β-unsaturated diazo compounds under metal-free conditions has been developed to synthesize 3-spirocyclopropyl-2-oxindole derivatives. The procedure is based on the 1,3-dipolar character of the corresponding diazo compounds under base-catalyzed conditions. The method has a wide substrate scope and uses easily available starting materials. [ABSTRACT FROM AUTHOR]

A chiral N,N′‐dioxide‐nickel(II) complex‐catalyzed asymmetric amination of 3‐bromo‐3‐substituted oxindoles with anilines has been developed. A series of alkyl or aryl 3‐amino‐indolinones with quaternary stereocenters were obtained in high yields with excellent ee values in one step (up to 99 % yield, up to 96 % ee). The method provided a ready route to optically active intermediates of 3‐amino‐2‐oxindole‐based bioactive compounds. Moreover, a possible transition‐state model is proposed so as to elucidate the origin of the chirality based on the X‐ray crystal structure of the catalyst and the adduct. [ABSTRACT FROM AUTHOR]

The first catalytic asymmetric multiple vinylogous addition reactions initiated by Meinwald rearrangement of vinyl epoxides were realized by employing chiral N,N′‐dioxide/ScIII complex catalysts. The vinyl epoxides, as masked β,γ‐unsaturated aldehydes, via direct vinylogous additions with isatins, 2‐alkenoylpyridines or methyleneindolinones, provided a facile and efficient way for the synthesis of chiral 3‐hydroxy‐3‐substituted oxindoles, α,β‐unsaturated aldehydes and spiro‐cyclohexene indolinones, respectively with high efficiency and stereoselectivity. The control experiments and kinetic studies revealed that the Lewis acid acted as dual‐tasking catalyst, controlling the initial rearrangement to match subsequent enantioselective vinylogous addition reactions. A catalytic cycle with a possible transition model was proposed to illustrate the reaction mechanism. [ABSTRACT FROM AUTHOR]

One-pot three-component cyclo-condensation reaction of bis(indole-2,3-diones) with dimedone, 3-methyl-1H-pyrazol-5(4H)-one, or 6-aminouracil in boiling acetic acid afforded bis-spirocyclic oxindoles linked to acridine, dipyrazolo[3,4-b:4',3'-e]pyridine, and pyrido[2,3-d:6,5-d']dipyrimidine, respectively. [ABSTRACT FROM AUTHOR]

A regio- and stereoselective method for the synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]-pyrrolidine-1,3'-oxindoles] in 24–79% yields, based on the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with azomethine ylides generated in situ from benzylamines and isatins by refluxing in CH2Cl2 for 24 h has been developed. 3-Phenyl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles] were obtained in 36–71% yields via the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromene, isatins, and L-phenylglycine proceeding in EtOH at 60°C for 5 h. The resulting compounds exhibited cytotoxic activity against human cervical cancer HeLa cells in the micromolar concentration range. [ABSTRACT FROM AUTHOR]

3-Aryloxindole derivatives were synthesized through a Friedel–Crafts-type cyclization. The reaction was catalyzed by a trimethylsilyl tricyanopalladate complex generated in situ from trimethylsilyl cyanide and Pd(OAc)2. Wide varieties of diethyl phosphates derived from N -arylmandelamides were converted almost quantitatively into oxindoles. When N , N -dibenzylamide was used instead of an anilide substrate, a benzo-fused δ-lactam was obtained. An oxindole product was subjected to substitution reactions to afford 3,3-diaryloxindoles with two different aryl groups. [ABSTRACT FROM AUTHOR]

An abnormal di-amination between isatin N,N′-cyclic azomethine 1,3-dipole and azodicarboxylates at the α-position of the cyclic amine and C3 of oxindole has been disclosed. This new protocol is tolerable for a series of substrates and 19 new 3-amino oxindoles were obtained in good yields (up to 85% yield) under mild conditions. [Display omitted] An abnormal di-amination between isatin N,N′ -cyclic azomethine 1,3-dipole and azodicarboxylates at the α-position of the cyclic amine and C3 of oxindole has been disclosed. This new protocol is tolerable for a series of substrates and 19 new 3-amino oxindoles were obtained in good yields (up to 85% yield) under mild conditions. [ABSTRACT FROM AUTHOR]

• Indolin-2-one derivatives were identified as a novel anti-tubercular agents. • The enzyme DprE1 exhibited strong binding interaction energies with the synthesized substances. • Molecular dynamic simulation trajectories were used to develop and validate protein-ligand complex stability characteristics under dynamic conditions. • The absorption-distribution-metabolism-excretion (ADME) values are favourable for all of the synthesized compounds. • Novel compounds with in vitro anti-mycobacterial action against Mycobacterium tuberculosis H37Rv (ATCC27294) include 9e (MIC: 1.56 μg/mL), 13b (MIC: 3.125 μg/mL), and 13e (MIC: 3.125 μg/mL). Tuberculosis (TB), which affects the lungs and other parts of the body, claims the lives of around 3 million people. Indolin-2-one derivatives were identified as a novel anti-tubercular series from Microplate Alamar Blue Assay (MABA) method, along with its synthesis, characterisation, molecular docking, and molecular dynamic simulations. The enzyme decaprenylphosphoryl-β-D-ribose 20-oxidase (DprE1) demonstrated high binding interaction energies associated with these compounds, which were investigated through the use of the docking technique. A conventional dynamic simulation study lasting 20 ns was used to assess the interaction's stability. The parameters derived from the trajectories of molecular dynamic simulation were computed and validated with respect to the stability of the protein-ligand complex under dynamic conditions. The absorption-distribution-metabolism-excretion (ADME) values are favourable for all of the synthesized compounds. After testing each novel compound for in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), the most promising lead analogues were 9e (MIC: 1.56 μg/mL), 13b (MIC: 3.125 μg/mL), and 13e (MIC: 3.125 μg/mL). In this study, we have designed and produced new 5-substituted Oxindole derivatives as anti-tubercular drugs through the application of docking and molecular dynamic modeling. Given the increasing demand for novel antibiotics and the ensuing urgent need for novel anti-TB medications, we think the currently reported oxindole derivatives of DprE1 inhibitors present an excellent possibility for future optimization. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • ER-targeted Oxifen upon conjugation with 5- acetoxyphenyl forms ACPOXF. • ACPOXF exhibits unique self-aggregation property. • The self-aggregation enabled ACPOXF to carry dexamethasone to form ACPOXF-De. • ACPOXF-Dex selectively kills even ER-negative colon cancer cells. • ACPOXF-Dex induces ROS, apoptosis and cell cycle arrest to kill colon cancer cells. • ACPOXF-Dex treatment increased survivability & decreased tumor volume in mice. Oxindoles are potent anti-cancer agents and are also used against microbial and fungal infections and for treating neurodegenerative diseases. These oxindoles are earlier established as estrogen receptor (ER)-targeted agents for killing ER (+) cancer cells. Our previously developed bis-arylidene oxindole, Oxifen (OXF) exhibits effective targeting towards ER (+) cancer cells which has a structural resemblance with tamoxifen. Herein, we have designed and synthesized few structural analogues of OXF such as BPYOX, ACPOX and ACPOXF to examine its cytotoxicity in different cancer as well as non-cancer cell lines and its potential to form self- aggregates in aqueous solution. Among these series of molecules, ACPOXF showed maximum toxicity in colorectal cancer cell line which are ER (-) but it also kills non-cancer cell line HEK-293, thereby reducing its cancer cell selectivity. Incidentally, ACPOXF exhibits self-aggregation, without the help of a co-lipid with nanometric size in aqueous solution. ACPOXF self-aggregate was co-formulated with glucocorticoid receptor (GR) synthetic ligand, dexamethasone (Dex) (called, ACPOXF-Dex aggregate) which could selectively kill ER (-) colorectal cancer cells and also could increase survivability of colon-tumour bearing mice. ACPOXF-Dex induced ROS up-regulation followed by apoptosis through expression of caspase-3. Further, we observed upregulation of antiproliferative factor, p53 and epithelial-to-mesenchymal (EMT) reversal marker E-cadherin in tumour mass. In conclusion, a typical structural modification in ER-targeting Oxifen moiety resulted in its self-aggregation that enabled it to carry a GR-ligand, thus broadening its selective antitumor property especially as colon cancer therapeutics. [ABSTRACT FROM AUTHOR]

Porous separators are essential for alkaline electrochemical energy technologies, such as alkaline water electrolyzers (AWEs). These separators are promising alternatives to dense membranes because they offer the potential for low cost and high ionic conductivity. However, two significant challenges in developing efficient and durable alkaline energy systems are the suppression of hydroxide ions-induced degradation and the reduction of gas permeation in porous separators. Compared to hydrophobic polysulfone (PSF), KOH-doped poly (oxindole biphenylene) (POBP) is a highly stable ion-solvating polymer that can conduct both potassium and hydroxide ions. Building upon this, a series of porous separators based on POBP polymer with different zirconia loads were designed using NIPS to investigate the chemical stability and water electrolysis performance where the Z60 separator exhibits remarkable characteristics, including low area resistance (0.227 Ω cm2), high bubble point pressure (0.813 MPa), low H 2 permeability (0.5 L min−1·cm−2) and exceptional 5040 h of ex-situ durability in 6 M KOH at 80 °C. Furthermore, the Z60 diaphragm showed a higher breaking time and lower weight loss after 261 h at 80 °C in the Fenton reagent, with the remaining mass being Z60 was 38 %. Notably, the Z60 diaphragm, when equipped with Ni–Al catalysts, achieved a current density of 0.5 A/cm2 at 1.7 V, which surpasses that of Zirfon (0.5 A/cm2 at 1.8 V). More importantly, when using Ni foam catalysts, the Z60 diaphragm demonstrated stable operation under 0.125 and 0.5 A/cm2 current densities at 80 °C for more than 900 h and 1200 h, significantly improving the durability of the porous separators. The results of this study showed that the blending of POBP can lead to the development of highly chemically stable porous diaphragms, thereby opening up a new avenue for advanced AWEs. This work developed POBP/ZrO 2 porous composite separators exhibited superior alkaline water electrolysis performance and excellent durability. [Display omitted] • The chemical stability of POBP/ZrO 2 porous composite separators was significantly improved. • The separator with thin skin layer showed low area resistance, high bubble point pressure and low H 2 permeability. • The Z60 diaphragm exhibited superior water electrolysis performance and excellent durability. [ABSTRACT FROM AUTHOR]

[Display omitted] Herein, we report the synthesis of thiolated methylene oxindoles via palladium-catalyzed intramolecular decarbonylative carbocyclization of thioester tethered alkyne. This reaction tolerates various functional groups, affording the thiolated methylene oxindoles in moderate-to-good yields. [ABSTRACT FROM AUTHOR]

[Display omitted] • 22 daphnane diterpenoidal oxazole derivatives were synthesized and evaluated for their anti-HCC cells activities. • YHC1 exhibited superior anti-HCC cells efficacy with low toxicity. • YHC1 induces cycle arrest, cellular senescence, apoptosis on Hep3B cells, and elevates cellular reactive oxygen species levels. • YHC1 can affect the interaction of the YAP-TEAD1 complex to inhibit the growth of HCC cells. Hepatocellular carcinoma (HCC) is a major challenge for human healthy. Daphnane-type diterpenes have attracted increasingly attention due to remarkable pharmaceutical potential including anti-HCC activity. To further develop this class of compounds as inhibitors of HCC, the daphnane diterpenoids 12- O -debenzoyl-Yuanhuacine (YHC) and 12-hydroxydaphnetoxin (YHE) were prepared by a standard chemical transformation from dried flower buds of the Daphne genkwa plant. Subsequently, 22 daphnane diterpenoidal 1,3,4-oxdiazole derivatives were rationally designed and synthesized based on YHC and YHE. The assessment of the target compound's anti-hepatocellular carcinoma activity revealed that YHC1 exhibited comparable activity to sorafenib in the Hep3B cell line, while demonstrating higher selectivity. The mechanistic investigation demonstrates that compound YHC1 induces cell cycle arrest at the G0/G1 phase, cellular senescence, apoptosis, and elevates cellular reactive oxygen species levels. Moreover, molecular docking and CETSA results confirm the interaction between YHC1 and YAP1 as well as TEAD1. Co-IP experiments further validated that YHC1 can effectively inhibit the binding of YAP1 and TEAD1. In conclusion, YHC1 selectively targets YAP1 and TEAD1, exhibiting its anti-hepatocellular carcinoma effects through the inhibition of their interaction. [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of 3,3′-disubstituted oxindoles having all-carbon quaternary stereocenters has been achieved using KOH as a base with an excellent diastereomeric ratio (98 : 2). The practicability of the present methodology has been validated with the synthesis of a series of substrates in good to excellent yields. The aesthetic simplicity, accessibility, and eco-friendly base (KOH) have prompted the broader application of the present methodology in organic synthesis. [ABSTRACT FROM AUTHOR]

Although transition metal phosphides are well studied as electrocatalysts and hydrotreating catalysts, the application of metal phosphides in organic synthesis is rare, and cooperative catalysis between metal phosphides and supports remains unexplored. Herein, we report that a cerium dioxide-supported nickel phosphide nanoalloy (nano-Ni2P/CeO2) efficiently promoted the C-3 alkylation of oxindoles with alcohols without any additives through the borrowing hydrogen methodology. Oxindoles were alkylated with various alcohols to provide the corresponding C-3 alkylated oxindoles in high yields. This is the first catalytic system for the C-3 alkylation of oxindoles with alcohols using a non-precious metal-based heterogeneous catalyst. The catalytic activity of nano-Ni2P/CeO2 was comparable to that reported for precious metal-based catalysts. Moreover, nano-Ni2P/CeO2 was easily recoverable and reusable without any significant loss of activity. Control experiments revealed that the Ni2P nanoalloy and the CeO2 support functioned cooperatively, leading to a high catalytic performance. [ABSTRACT FROM AUTHOR]

The acetic acid promoted reaction of 3-hydroxy-3-(indol-3-yl)indolin-2-ones and mercapto-substituted β-enamino esters showed very interesting molecular diversity. The reaction in ethanol at room temperature in the presence of acetic acid resulted in two diastereoisomeric 3,3-disubstituted oxindoles in high yields. When the reaction was carried out in refluxing ethanol, the reaction with 3-hydroxy-3-(indol-3-yl)indolin-2-ones with N-alkyl groups gave polycyclic spirooxindoles in satisfactory yields. However, a similar reaction with 3-hydroxy-3-(indol-3-yl)indolin-2-ones with NH groups afforded functionalized dihydroindolo[3,2-c]phenothiazines with sequential ring-opening of oxindole. A plausible domino annulation mechanism was rationally proposed for the formation of different kinds of polycyclic compounds. [ABSTRACT FROM AUTHOR]

An enantioselective ring-opening formal [3+2]-cycloaddition of spirovinylcyclopropyl oxindoles with enals via synergistic catalysis of palladium(0) and a chiral organocatalyst has been developed, affording spirooxindoles bearing four contiguous stereocenters in good yields with excellent enantioselectivities. The generality and utility of the protocol were also demonstrated through scale-up experiments and synthetic transformation of the resulting cycloadduct. [ABSTRACT FROM AUTHOR]

A Michael-initiated ring-closure reaction of pyridinium salts with arylidene oxindoles has been developed. A wide range of aryl-substituted spirocyclopropane oxindoles has been achieved in moderate to good yields (41–99%). This efficient strategy exhibits good functional group compatibility and may serve as an attractive method for the synthesis of diverse cyclopropanes. [ABSTRACT FROM AUTHOR]

An environmentally benign and proficient electro‐oxidative tandem azidation‐radical cyclization strategy is reported. Manganese‐catalyzed electrochemical reaction in an undivided cell at room temperature and the use of NaN3 as the cheapest azide source are the key features of this protocol. Using this approach, a series of oxindole and quinolinone derivatives are synthesized in high yields. The synthesized azide functionality was efficiently converted to various valuable derivatives. [ABSTRACT FROM AUTHOR]

The use of functionalized aldimines has been demonstrated as newly structural 1,4‐dipole precursors under carbene catalysis. More importantly, enantiodivergent organocatalysis has been successfully developed using carbene catalysts with the same absolute configuration, leading to both (R)‐ and (S)‐ enantiomers of six‐membered heterocycles with quaternary carbon centers. This strategy features a broad substrate scope, mild reaction conditions, and good enantiomeric ratio. DFT calculation results indicated that hydrogen bond C−H⋅⋅⋅F interactions between the catalyst and substrate are the key factors for controlling and even switching the enantioselectivity. These new 1,4‐dipoles can also react with isatin and its imines under carbene catalysis, allowing for access to the spiro oxindoles with excellent enantiomeric ratios. [ABSTRACT FROM AUTHOR]

A facile synthesis of isatin‐hydrazones from 3‐diazo oxindoles and sulfoxonium ylides under catalyst‐ and additive‐free conditions is described. A plausible reaction pathway is proposed for the transformation, in which diazo compounds play as electrophiles to react with nucleophilic sulfoxonium ylides. The reaction mechanism is supported by the experimental evidence. [ABSTRACT FROM AUTHOR]

In this review we compare and discuss results of compounds already reported as anticancer agents based on isatin-derivatives, metalated as well as non-metallated. Isatin compounds can be obtained from plants, marine animals, and is also found in human fluids as a metabolite of amino acids. Its derivatives include imines, hydrazones, thiosemicarbazones, among others, already focused on numerous anticancer studies. Some of them have entered in pre-clinical and clinical tests as antiangiogenic compounds or inhibitors of crucial proteins. As free ligands or coordinated to metal ions, such isatin derivatives showed promising antiproliferative properties against different cancer cells, targeting different biomolecules or organelles. Binding to metal ions usually improves its biological properties, indicating a modulation by the metal and by the ligand in a synergistic process. They also reveal diverse mechanisms of action, being able of binding DNA, generating reactive species that cause oxidative damage, and inhibiting selected proteins. Strategies used to improve the efficiency and selectivity of these compounds comprise structural modification of the ligands, metalation with different ions, syntheses of mononuclear and dinuclear species, and use of inserted or anchored compounds in selected drug delivery systems.

Base assisted divergent reactivity of isatins and allenoates has been achieved, which afforded diastereoselective spirofuran oxindoles and γ-functionalized allenoates. The DBU mediated Morita–Baylis–Hillman (MBH) reaction followed by the cascade annulation through the stabilized β-ammonium enolate intermediate led to the spiro-framework, wherein DABCO furnished the γ-functionalized allenoates. The protocol offers access to biologically relevant functionalized oxindole scaffolds with an excellent substrate scope under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Spirocyclopropyl oxindole represents an emerging framework by unique amalgamation of versatile 2‐oxindole motif and highly strained cyclopropane unit. This scaffold is remarkable for its diverse medicinal and synthetic applications. The present review delivers a comprehensive overview of the strategies to afford spirocyclopropyl oxindoles and their potential synthetic transformations. The syntheses of spirocyclopropyl oxindoles have been described based on the type of precursors, including isatin, 3‐alkenyl oxindole, diazooxindole, oxindole, and 3‐chlorooxindole. Besides, the utility of different cyclopropanation reagents like sulfur ylide, MBH‐carbonate, carbenoid, vinyl selenone, etc. have also been emphasized. Furthermore, various ring‐expansion/opening reactions of spirocyclopropane oxindoles using dipolarophiles/nucleophiles have critically been illustrated. [ABSTRACT FROM AUTHOR]

Direct arylation methods have been used to polymerize thienylmethylene oxindoles (TEIs) and 3,3-bis[[(2-ethylhexyl)oxy]methyl]-3,4-dihydro-2H-thieno-[3,4-b][1,4]dioxepin (ProDOT) for new donor-acceptor conjugated polymers. The polymers exhibited blue hues in neutral-state with distinct color-to-transmissive reversible electrochromic switching under applied potentials from 0 V to +1.5 V, and showed high coloration efficiencies (436–438 cm2·C−1) in near-infrared regions with high switching speeds around 1–2 s under ambient conditions. [ABSTRACT FROM AUTHOR]

A synthesis of a series of novel fused tricyclic heterocyclic compounds has been achieved in one-pot reaction set up starting from (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one and 1,4-benzoxazinone/quinoxalinone derivatives promoted by tin(IV) chloride. The reaction is supposed to occur via a sequential intermolecular Michael addition of the 1,4-benzoxazinone derivatives to the oxindoles, intramolecular cyclization, and aromatization with the elimination of water. Apart from spectroscopic characterization, the structure of one of the pyrrolo[1,4]benzoxazinone derivative is confirmed by single-crystal X-ray diffraction. Thus, the developed domino protocol provides easy access to multifunctional pyrrolo[1,4]benzoxazines in one-pot with high efficiency. [ABSTRACT FROM AUTHOR]

A visible light induced highly convenient and practical method for the trifluoromethyl–arylation of N-arylmethacrylamides has been developed using Umemoto's reagent as the trifluoromethyl source. This user-friendly approach can proceed under visible light irradiation without any transition metal, photocatalyst and additive at room temperature. The strategy presented here provides access to trifluoromethylated oxindoles in good to excellent yields with a broad functional group tolerance. Preliminary mechanistic experiments indicated that the reaction process involves a homolytic cleavage of Umemoto's reagent irradiated by visible light. [ABSTRACT FROM AUTHOR]

Reported herein is an unexpected construction of functionalized π-extended indolizine polycycles through a one-pot two-step cascade process comprising the base-promoted dearomative [3+2] cycloaddition of quinilinium salts and 3-alkenyl oxindoles, followed by a DDQ-mediated oxidative decarbonylation. Moreover, we could achieve the substrate-controlled diverse synthesis of structurally strained cyclopropane spirooxindole by using pyridinium salts as starting materials. [ABSTRACT FROM AUTHOR]

The tandem cyclization of acrylamide with diselenides facilitated by electrochemical oxidation was successfully developed. This strategy provided an environmentally friendly method for the construction of C−Se bond. A series of seleno oxindoles with pharmacological activity were obtained by using this well‐designed tandem cyclization strategy. The in vitro antitumor activity of the compounds was also screened through MTT assay. Results showed that the seleno oxindoles exhibited better antitumor activity than other oxindole derivatives. [ABSTRACT FROM AUTHOR]

One-pot, three-component reactions of the tricyclic isatin 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione with variously substituted aryl cyanomethyl ketones and malononitrile, or ethyl cyanoacetate, generates spiro[4H-pyran-3,3'-oxindoles], such as, 2-amino-2'-oxo-6-(phenyl)-5',6'-dihydro-2'H,4'H-spiro[pyran-4,1'-pyrrolo[3,2,1-ij]quinoline]-3,5-dicarbonitrile. [ABSTRACT FROM AUTHOR]

An efficient decarboxylative addition reaction of β‐ketoacids with miscellaneous electrophiles in 2,2,2‐trifluoroethanol (TFE) is reported. The reaction proceeds smoothly without any base and metal catalysts, affording a broad range of diarylmethanes, β‐hydroxy ketones and 3,3‐disubstituted oxindoles with moderate to excellent yields under essentially neutral conditions. [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease. Methods: 1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones ( 6-7 ) were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites. Results: Compound 6g was the strongest inhibitor against both AChE ( K i  = 0.35 μM) and BuChE ( K i  = 0.53 μM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound 7m had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE ( K i  = 0.69 μM) and BuChE ( K i  = 0.95 μM). Conclusion: The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects.

Natural products and their analogues are significant sources of therapeutic lead compounds. However, synthetic strategies for generating large collections of these molecules remain a significant challenge. The most difficult step in their synthesis is the design of a common intermediate that can be easily transformed into natural products belonging to different families. This study demonstrates the evolution of synthetic tactics designed to assemble the functionalized piperidines present in indole alkaloids from a common intermediate. More importantly, we also report a previously unknown Ir- and Er-catalyzed dehydrogenative spirocyclization reaction that enables direct access to spirocyclic oxindole alkaloids. As a practical application, the asymmetric total syntheses of 29 natural alkaloids belonging to different families were accomplished by following a uniform synthetic route. The proposed methodology extends the capability of the iridium-catalyzed dehydrogenative coupling reaction to the realm of indole-alkaloid synthesis and provides new opportunities for the efficient preparation of natural product-like molecules.

A novel synthetic route for the construction of (E)‐3‐alkylideneindolin‐2‐ones through iron‐catalyzed aerobic oxidative condensation of oxindoles with benzylamines has been developed. This oxidative reaction involves a sequence of C–H activation, amine self‐condensation, nucleophilic addition, and C–C double bond formation. The synthetic importance of this protocol has been demonstrated by preparing tyrosine kinase inhibitors, anticonvulsant and antitumor agents, and other valuable 3‐alkylideneindolin‐2‐one derivatives. Key intermediates are isolated and a plausible mechanistic pathway for the reaction has been discussed. [ABSTRACT FROM AUTHOR]

A novel one-pot method to prepare 3-hydroxy-2-oxindoles via acyloin rearrangements of 2-hydroxy-indolin-3-ones generated in situ from 2-alkynyl arylazides has been described. The reaction was accomplished to afford a variety of 3-hydroxy-2-oxindole derivatives in moderate to good yields under mild conditions. [ABSTRACT FROM AUTHOR]

A silver tetrafluoroborate catalyzed domino cycloisomerization–vinylogous aldol addition sequence on a multifunctional substrate such as ortho-alkynylbenzaldehydes yielding functionalized 1H-isochromenes in a single step with high yield and excellent diastereoselectivity (>19 : 1) is described. The reaction was well tolerated by alkyl, aryl, and unsubstituted alkynylbenzaldehydes, and furnished selective 6-endo-dig adducts exclusively without loss in the regio- as well as diastereoselectivity. [ABSTRACT FROM AUTHOR]

Hydroxyl-containing compounds are highly value-added organic molecules, and the establishment of novel methodologies for their elaboration is a long-standing challenge in organic synthesis. Here the first oxone-mediated direct arylhydroxylation of activated alkenes was developed for the synthesis of valuable hydroxyl-containing oxindoles and 3,4-dihydroquinolin-2-ones. The products were controlled by adjusting the structure of the starting alkenes. Moreover, the reaction was performed under simple conditions without any external additives or catalysts. Primary mechanistic studies showed that this reaction was a tandem process involving epoxidation and subsequent Friedel–Crafts alkylation, and oxone played a dual role (both the oxidant and proton source) in this process. [ABSTRACT FROM AUTHOR]

Candida antarctica (CAL‐B) lipase‐catalyzed resolution of 1,3‐dialkyl‐3‐hydroxymethyl oxindoles has been performed to obtain (R)‐1,3‐dialkyl‐3‐acetoxymethyl oxindoles with up to 99% ee and (S)‐1,3‐dialkyl‐3‐hydroxymethyl oxindoles with up to 78% ee using vinyl acetate as acylating agent and acetonitrile as solvent transforming (S)‐3‐allyl‐3‐hydroxymethyl oxindole to (3S)‐1′‐benzyl‐5‐(iodomethyl)‐4,5‐dihydro‐2H‐spiro[furan‐3,3′‐indolin]‐2′‐one. The optically active 3‐substituted‐3‐hydroxymethyl oxindoles and spiro‐oxindoles are among the key synthons in the synthesis of potentially biologically active molecules. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach to identify a bis-benzodioxolylindolinone (azoffluxin) that synergizes with fluconazole against C. auris. Azoffluxin enhances fluconazole activity through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels. This activity is conserved across most C. auris clades, with the exception of clade III. Azoffluxin also inhibits efflux in highly azole-resistant strains of Candida albicans, another human fungal pathogen, increasing their susceptibility to fluconazole. Furthermore, azoffluxin enhances fluconazole activity in mice infected with C. auris, reducing fungal burden. Our findings suggest that pharmacologically targeting Cdr1 in combination with azoles may be an effective strategy to control infection caused by azole-resistant isolates of C. auris.

The synthesis of spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles.

The photochemical deracemization of spiro[cyclopropane‐1,3′‐indolin]‐2′‐ones (spirocyclopropyl oxindoles) was studied. The corresponding 2,2‐dichloro compound is configurationally labile upon direct irradiation at λ=350 nm and upon irradiation at λ=405 nm in the presence of achiral thioxanthen‐9‐one as the sensitizer. The triplet 1,3‐diradical intermediate generated in the latter reaction was detected by transient absorption spectroscopy and its lifetime determined (τ=22 μs). Using a chiral thioxanthone or xanthone, with a lactam hydrogen bonding site as a photosensitizer, allowed the deracemization of differently substituted chiral spirocyclopropyl oxindoles with yields of 65–98 % and in 50–85 % ee (17 examples). Three mechanistic contributions were identified to co‐act favorably for high enantioselectivity: the difference in binding constants to the chiral thioxanthone, the smaller molecular distance in the complex of the minor enantiomer, and the lifetime of the intermediate 1,3‐diradical. [ABSTRACT FROM AUTHOR]

A novel microfluidic visible‐light process for the functionalisation of oxindoles is reported. The chemistry is based on the reactivity of the corresponding enol ethers, which participate in a site‐, regio‐ and diastereoselective [2+2] heterocycloaddition (Paternò–Büchi) process. The mild reaction conditions, the use of available ketones, together with the high generality (23 examples) and robustness (up to gram scale) make this process a useful synthetic platform for the construction of structurally strained heterocycles. [ABSTRACT FROM AUTHOR]