Selective C3-alkenylation of oxindole with aldehydes using heterogeneous CeO2 catalyst

We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields(87%–99%) and high stereoselectivities(79%–93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction.

Two New Oxindole Alkaloids from Ervatamia yunnanensis

Two new oxindole alkaloids. 17-demethoxy-hydroisorhynchophylline 1 and 17-demethoxy-hydroisorhynchophylline N-oxide 2, have been isolated from the aerial parts of Ervatamin yunnanensis, and their structures were elucidated on the basis of spectroscopic analysis.

Synthesis of spiropyrrolidine oxindoles through Rh(Ⅱ)-catalyzed olefination/cyclization of diazooxindoles and vinyl azides

A simple and efficient process involving the Rh(II)-catalyzed[1+1+3]annulation of diazooxindoles and vinyl azides has been developed for the synthesis of spiropyrrolidine oxindoles with potential biological activity and significant synthetic applications.This process involves a novel rhodium-catalyzed olefination of diazo compounds,followed by annulation with vinyl azides.This method is compatible with a broad range of substrates and affords moderate to good yields under mild reaction conditions.

Photoinduced Dehalocyclization to Access Oxindoles Using Formate as a Reductant

Herein,we report an efficient and practical protocol for the photoinduced dehalocyclization of ortho-halophenylacrylamides with formate by the engagement of a CO_(2) radical anion to access substituted oxindoles.This method proceeds smoothly under mild conditions and exhibits a wide range of substrate as well as remarkable functional group compatibility.

Regio-and enantioselective conjugate addition ofβ-nitroα,β-unsaturated carbonyls to construct 3-alkenyl disubstituted oxindoles

Reversal of regioselectivity in the catalytic asymmetric conjugate additions of 3-substituted oxindoles toβ-nitroenones orβ-nitroacrylates was established with chiral scandium catalysts.It enabled the construction of functionalized 3,3-disubstituted oxindoles,including terminal and internal vinyl groups in excellent yields and ee values.

Convenient Synthesis of Thioester-Substituted Oxindoles by Palladium-Catalyzed Thiocarbonylative Cyclization with Sulfonyl Chlorides as the Sulfur Source

A general and straightforward strategy for the synthesis of thioester-substituted oxindoles via a palladium-catalyzed thiocarbonyla-tive cyclization process has been developed.With sulfonyl chlorides as promising sulfur source,a wide range of thioester-substituted oxindoles were obtained in moderate to high yields.Both aryl and alkyl sulfonyl chlorides were well tolerated,and Mo(CO)6 played a dual role as both a CO source and a reductant in this approach.

Metal-ligand cooperative iridium complex catalyzed C-alkylation of oxindole and 1,3-dimethylbarbituric acid using alcohols

A general and high-efficiency C-alkylation of oxindoles and barbituric acids has been developed by a Cp*Ir complex[Cp*Ir(2,20-bpyO)(OH)]Na with a bipyridine-based functional ligand.In particular,H_(2)O was selected as the solvent instead of the organic solvent in this catalytic system.Through mild reaction conditions gave a variety of corresponding alkylated heterocyclic compounds with good to excellent yields.More importantly,the gramscale C-alkylation reaction was successfully carried out with good yield using a common route with only a single purification by column chromatography.

Pincer iridium(Ⅲ)-catalyzed enantioselective C(sp3)-H functionalization via carbenoid C–H insertion of 3-diazooxindoles with 1,4-cyclohexadiene

The asymmetric carbenoid C–H insertion of 3-diazooxindoles into 1,4-cyclohexadiene has been accomplished in the presence of chiral bis(imidazoline) NCN pincer iridium(Ⅲ) complexes as the catalysts. With a catalyst loading of 0.5 mol%, the reactions proceeded smoothly at 0℃ to afford a variety of chiral 3-substituted oxindoles in good yields with moderate to excellent enantioselectivities(up to 99% ee). The protocol exhibits good functional group tolerance with respect to 3-diazooxindoles and is readily scaled up to 2 mmol scale without any loss in activity and enantioselectivity. Density functional theory(DFT)calculations have been performed to better understand the reaction mechanism and to explain the stereochemical outcome of the reactions.

A spirocyclic oxindole analogue:Synthesis and antitumor activities

A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3＇-pyrrolol2,3-b]pyridin]-2＇（1＇H）-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 （IC50 = 50 nmol/L）.

Copper-catalyzed Meerwein carboarylation of alkenes with anilines to form 3-benzyl-3-alkyloxindole

A simple and direct route for double C–C bond formation by copper-catalyzed Meerwein carboarylation process has been developed. In the presence of Cu I(5 mol%), tert-butyl nitrite and anilines, a wide variety of N-arylacrylamides underwent tandem Meerwein arylation/C–H cyclization to produce pharmaceutically important 3-benzyl-3-alkyloxindole in moderate to good yield.

On Water： Bronsted Acidic Ionic Liquid [（CH2）4SO3HMIM][HSO4] Catalysed Synthesis of Oxindoles Derivatives

Some oxindoles derivatives are synthesized from the condensation of indoles with isatins in the presence of green and recycable catalyst [（CH2）4SO3HMIM] [HSO4] in water at room temperature.

Asymmetric Double Michael Reaction Catalyzed by Simple Primary Amine Catalysts： A Straightforward Approach to Construct Spirocyclic Oxindoles

The enantioselective double Michael reaction of N-Boc-3-nonsubstitued oxindoles with dienones catalyzed by chiral monoimide protected cyclohexane-1,2-diamines was developed. A wide range of optically active spirocyclic oxindoles were obtained up to 98% yield and up to 89% ee.

Pd-Catalyzed 2,3-Allenylation of Oxindoles with 2,3-Allenylic Carbonates

Allenes and oxindoles are two classes of very important compounds for medicinal chemistry and organic chemistry.Thus,it is of high interest to combine an allene and an oxindole into one molecule.Herein,the first example of palladium-catalyzed exclusive 2,3-allenylation reaction of oxindoles with 2,3-allenylic carbonates has been successfully developed.A rationale for the selectivity of 2,3-allenylation over the expected 1,3-alkadienylation has been proposed.

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids:Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel-nickel/bisphosphinecatalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids.Racemic spiroepoxyoxindoles were converted to chiral homoallylic alcohols bearing quaternary carbon stereogenic centers via a stereoablative enantioconvergent transformation.The subsequently fabricated oxindoles-carrying quaternary carbon products were obtained in good yields and enantioselectivity.A wide range of substrates and alkenylboronic acids was tolerated under the catalytic system.This reaction provided a rare example of a nickelcatalyzed enantioselective cross-coupling reaction of tertiary alkyl electrophiles and an enantioconvergent transformation of racemic epoxides,beneficial as a low-cost,sustainable,and efficient catalyst in the preparation of chiral oxindole-containing natural and pharmaceutical compounds.

N-Heterocyclic Carbene-Catalyzed 1,6-Addition of Homoenolate Equivalent Intermediates: Asymmetric Synthesis of Nonspirocyclic Quaternary Oxindoles

Although there is a growing interest in developing asymmetric 1,6-addition reactions of carbon nucleo-philes to Michael acceptors,the corresponding 1,6-addition of homoenolates remains an unsolved problem.Currently,the N-heterocyclic carbene(NHC)-catalyzed cycloadditions of homoenolate equivalent intermediates have achieved widespread success.However,considerable limitations still exist for the linear reactions with electron-deficient alkenes,which are limited to 1,4-Michael acceptors.This report presents the first NHC-catalyzed asym-metric homoenolate addition of enals to 1,6-Michael acceptors.The strategy leads to the challenging nonspirocyclic 3,3-disubstituted oxindoles with two adjacent stereocenters,a quaternary and a trisubsti-tuted one,in good yields and high stereoselectivities with a wide variety of substrates.

Allylation and alkylation of oxindoleketimines via imine umpolung strategy

When treated with an alkoxide base like t-BuOK in aprotic solvent,N-di phenyl methyl imino oxindoles,made conveniently through condensation of corresponding isatins with N-di phenyl methyl amine,are deprotonated to form azaallyl anions.Allylation and alkylation of this type of intermediates proceed smoothly with diverse C-electrophiles.Acidic work up finishes 3-amino-3-allyl/alkyl oxindoles.The overall transformation equals to an umpolung process at the C3 of isatins.

Chincona Alkaloid-Catalyzed Enantioselective Trifluoromethylthiolation of Oxindoles

An organocatalytic asymmetric trifluoromethylthiolation of 3-aryl or 3-alkyloxindoles employing a trifluoromethyl-substituted thioperoxide as the electrophilic trifluoromethylthiolating reagent was described.Reactions occurred in good to excellent enantioselectivities to generate oxindoles with a SCF_(3)-substituted quaternary chiral center.

Organocatalytic asymmetric [3+3] annulation of isatin N,N’-cyclic azomethine imines with enals:Efficient approach to functionalized spiro N-heterocyclic oxindoles

An unprecedented chiral secondary amine-catalyzed [3+3] annulation of isatin N,N’-cyclic azomethine imines with α,β-unsaturated aldehydes was developed.This strategy allowed the construction of structurally novel spiro N-heterocyclic oxindole derivatives in good yields(up to 91%) and good to excellent enantioselectivities(up to>99% ee),albeit with modest diastereoselectivities(up to 3.1:1 dr).

N-Heterocyclic Carbene-Catalyzed All Carbon-[4+2] Cyclocondensation of α,β-Unsaturated Acyl Chlorides with 3-Alkylenyloxindoles

Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles,the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established.In this note,the NHC-catalyzed all carbon[4+2]cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles was developed to give the corresponding spirocarbocyclic oxindoles in good yield with good to high diastereoselectivities.