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We have developed a convenient synthetic protocol for efficient construction of significant dihydrobenzofuran and benzofuran scaffolds by Lewis base-mediated annulation reaction ortho -iminophenols and ortho -vinylphenols with MBH carbonates of isatins under mild and metal-free conditions. The selective generation of different kinds of dihydrobenzofuran and benzofuran derivatives was successfully achieved by employing different substituted isatin-derived MBH carbonates with ortho - N -tosyliminophenols and ortho -vinylphenols. The features included broad substrate scopes, excellent functional group compatibility, high molecular diversity, and atomic economy.

A novel and highly efficient Pd-catalyzed arylation of sulfenate anions with aryl thianthrenium salts is demonstrated. This procedure provides a practical protocol to synthesize various diaryl and alkyl aryl sulfoxides in moderate-to-good yields. The new approach shows mild reaction conditions, broad substrate scope, and good functional group tolerance.

A convenient synthetic protocol for diverse fused chromenes was successfully developed by a three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and various cyclic 1,3-dipolarophiles containing o -hydroxyphenyl group. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and 3-( o -hydroxyarylidene)indolin-2-ones in tetrahydrofuran at 60 °C resulted in unique functionalized spiro[cyclobuta[ c ]chromene-1,3'-indolines] in good yields and with high diastereoselectivity. However, the similar three-component reaction with 2-(5-halo-2-hydroxyarylidene)indolin-2-ones afforded unexpected chain products in satisfactory yields. In addition, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and 2-( o -hydroxyarylidene)-1,3-indanediones in tetrahydrofuran at 60 °C resulted in complex indeno[2',1':5,6]pyrano[3,4- c ]chromene derivatives in high yields and with high diastereoselectivity.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3- b ]pyridine-3,4b,5,6,7(1 H )-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3- b ]pyridine-3,4b,5,6,7(1 H )-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine., (Copyright © 2024, Chen et al.)

We have developed an efficient protocol for the synthesis of spiro[indoline-pyridine]dicarboxylates and substituted alkylidene oxindoles through [3 + 3] cycloaddition and Michael addition individually by azomethine ylides and various MBH carbonates of isatins. The selective generation of cyclic products and chain products was achieved by changing the substituents at the 3-position of the oxindoles. The features of this method include convenient catalysts, mild reaction conditions, and broad substrate scopes.

A highly efficient palladium-catalyzed asymmetric tandem aza-Heck/Sonogashira coupling reaction of O -phenyl hydroxamic ethers with terminal alkynes is described. This protocol enables versatile access to challenging chiral isoindolinone derivatives bearing a quaternary stereogenic center. The palladium-catalyzed aminoalkynylation reaction shows broad functional group tolerance and allows the straightforward preparation of isoindolinones with high efficiency and excellent enantioselectivity under mild conditions. DFT calculations were performed to disclose the reaction mechanism and the origins of the enantioselectivity.

A highly robust, general, and practically simple palladium-catalyzed domino bicyclization strategy is presented to synthesize nitrogen-containing bis-heterocycles bearing methylene indole motifs from alkyne-tethered carbamoyl chlorides and β,γ- or γ,δ-unsaturated hydrazones. The salient features of this transformation include broad substrate scope, good functional group tolerance, ease for scale-up, and convenient conversion.

A straightforward synthetic protocol for the efficient construction of diazepine-containing spiroindolines has been developed and proceeds through a by base-promoted annulation reaction of α-halogenated N -acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes. Additionally, the similar reaction with α-halogenated N -tosylhydrazones also afforded N -tosyl-substituted spiro[indoline-3,5'-[1,2]diazepine] in satisfactory yields. This protocol provides a convenient approach for the assembly of diverse highly functionalized spiro[indoline-3,5'-[1,2]diazepines] and also features a broad substrate scope, simple reaction conditions, and high molecular convergence., (Copyright © 2023, Liu et al.)

Oxazines are an important class of compounds in oxazine ligands and medical chemistry. Here, we describe a linear-selective allylation of imines with allyl electrophiles via cross-electrophile coupling reactions, followed by cyclization with halogenated reagents, providing a new strategy to afford oxazine compounds with a tetrasubstituted carbon center. Mechanistic studies indicate that α-amino carbanion, generated by successive single-electron transfer processes, is a key intermediate for nucleophile attack on π-allylpalladium in photoredox/palladium catalysis.

A convenient synthetic protocol for regioselective and diastereoselective construction of complex dispiro-indanone-fluorenone-oxindole motifs was developed by the base-promoted annulation reaction of bindone and MBH carbonates of isatins by adjusting reaction conditions. DABCO promoted the annulation reaction of bindone and MBH carbonates of isatins in DCM at room temperature, affording dispiro[indene-2,4'-fluorene-1',3″-indoline] derivatives in good yields and with high diastereoselectivity. Triethylamine promoted the annulation reaction of two molecular 1,3-indanediones and MBH esters of isatins in ethanol at elevated temperature and selectively gave dispiro[indene-2,4'-fluorene-3',3″-indolines] in moderate yields. However, triethylamine promoted the annulation reaction of excess 1,3-indanediones and MBH esters of isatins in refluxing ethanol, affording dispiro[indene-2,4'-fluorene-3',3″-indolines] with the Z -isomer as the major product and the E -isomer as the minor product.

An iodine-promoted domino reaction of arylamines/benzylamines, dialkyl but-2-ynedioates and 3-hydroxy-3-(indol-3-yl)indolin-2-ones showed very interesting molecular diversity. The reaction in acetonitrile at 65 °C in the presence of 30% mmol I 2 resulted in spiro[indoline-3,1'-pyrido[4,3- b ]indoles] in satisfactory yields. When anilines without para -substituents were used in the reaction, a direct substitution of the hydroxyl group to 2-(phenylamino)maleate at the para -position of aniline gave chain products in good yields. Additionally, similar reactions with benzylamines not only gave spiro[indoline-3,1'-pyrido[4,3- b ]indoles], but also afforded spiro[indoline-3,1'-pyrano[4,3- b ]indol]-2-ones in lower yields. A plausible domino annulation mechanism was rationally proposed for the formation of different kinds of polycyclic compounds.

The domino reaction of alkyl and aryl isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C resulted in unique functionalized spiro[dibenzo[ a , f ]azulene-6,2'-indenes] in good yields, in which the two 2-arylidene-1,3-indanediones acted as different building blocks to construct the polycyclic system. More importantly, the unprecedented anticipation of the ortho-position of benzylidene group to form a novel dibenzo[ a , f ]azulene ring through a formal [5 + 2] cycloaddition process was first observed. On the other hand, DABCO-promoted reaction of the isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C afforded functionalized spiro[cyclopenta[ a ]-indene-2,2'-indene] derivatives.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Platinum(II)-based metallacycles/cages have obtained tremendous attention due to their fascinating topology and wide range of applications, such as fluorescent materials, cell imaging, and tumor treatment. In this work, a metallatetragon ( 1 ) was constructed from 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine ( 2 ) and 90° cis -Pt(II) ( Pt ) in acetone through the strategy called "coordination driven self-assembly". Interestingly, through co-assembly of 1 and poly(ethylene glycol)-modified tetraphenylethylene ( TPE-PEG 22 ), fluorescent nanotheranostics, which could generate singlet oxygen ( 1 O 2 ) under the NIR irradiation and release Pt drugs under a low-pH microenvironment, were prepared successfully. The obtained theranostics could realize living cell imaging and synergistic chemo-photodynamic therapy in vitro and in vivo .

A convenient synthetic procedure for the construction of novel dispirooxindole motifs was successfully developed by base-promoted three-component reaction of ammonium acetate, isatins and in situ-generated 3-isatyl-1,4-dicarbonyl compounds. The piperidine-promoted three-component reaction of ammonium acetate, isatins and the in situ-generated dimedone adducts of 3-ethoxycarbonylmethyleneoxindoles afforded mutlifunctionalized dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione substituent. A plausible reaction mechanism is proposed to explain the formation of the different spirooxindoles., (Copyright © 2023, Xiao et al.)

Diverse functionalized dihydrobenzofuran spiro-indanedione-oxindole scaffolds were conveniently synthesized by base-promoted cyclization reaction of Morita-Baylis-Hillman (MBH) carbonates of isatins and 2-( o -hydroxybenzylidene)-1,3-indanediones. The two diastereomeric dispiro[indene-2,1'-cyclopenta[ b ]benzofuran-2',3″'-indolines] could be selectively synthesized by using DABCO or DMAP as a base promoter. More importantly, DABCO or DMAP facilitated the annulation reaction of MBH formates of isatins and 2-( o -hydroxybenzylidene)-1,3-indanediones selectively, resulting in spiro[cyclopropa[ c ]chromene-1,2'-indene]-1',3'-diones or dispiro[indene-2,1'-cyclopenta[ b ]benzofuran-2',3″'-indolines]. Additionally, a similar reaction with MBH maleimides of isatins afforded dispiro[indene-2,5'-benzofuro[2',3':1,5]cyclopenta[1,2- c ]pyrrole-4',3″'-indolines] in high yields and with high diastereoselectivity.

The base promoted tandem annulation reaction of activated cyclic 1,3-dipolarophiles such as 2-arylidene-1,3-indanediones, 2-( o -hydroxybenzylidene)-1,3-indanediones and 3-methyleneoxindoles with functionalized furo[2,3- d ]pyrimidine-2,4-diones was systematically investigated. This reaction provided efficient synthetic protocols for complex dispiro/dispiro fused tricyclic compounds including dispiro[indene-2,3'-cyclopentane-1',5''-pyrimidines], dispiro[indoline-3,3'-cyclopentane-1',5''-pyrimidines] and spiro[cyclopenta[ c ]indeno[1,2- b ]chromene-3,5'-pyrimidines] in good yields and with high diastereoselectivity. The reaction was believed to proceed via sequential ring-opening of the furyl ring, formal [3 + 2] cycloaddition and annulation of the o -hydroxyphenyl group.

Pd/Cu-catalyzed cascade Heck-type reactions of alkenyl halides with terminal alkynes have been developed. This research provides an efficient atom-economical approach to access a variety of highly substituted pyrrolidines in moderate to good yields. This protocol features readily available substrates, broad substrate scope, easy scale-up, high selectivities and versatile transformations.

A highly efficient Pd-catalyzed carboetherification reaction of β,γ-unsaturated ketoximes with propargylic acetates is demonstrated. This method provides a practical protocol for accessing the incorporation of an allene moiety into 3,5-disubstituted and 3,5,5-trisubstituted isoxazolines. The salient features of this transformation include a broad substrate scope, good functional group tolerance, an easy scale-up, versatile transformations, and applications in the late-stage modification of drugs.

The three-component reaction of isoquinolines, dialkyl acetylenedicarboxylates, and 5,6-unsubstituted 1,4-dihydropyridines in acetonitrile at room temperature afforded functionalized isoquinolino[1,2- f ][1,6]naphthyridines in good yields and with high diastereoselectivity. More importantly, the formal [2 + 2] cycloaddition reaction of dialkyl acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[ b ]pyrroles as minor products via further rearrangement., (Copyright © 2023, Chen et al.)

Metal nanoparticle catalysts have attracted great interest because they possess high surface-to-volume ratios and exhibit a very large number of catalytically active sites per unit area. However, high surface-to-volume ratios will induce nanoparticle aggregates during the catalytic reactions, making them lose their catalytic activity. In this work, a monoterpyridine-unit-functionalized pillar[5]arene (TP5) was synthesized successfully, which can be used as anchoring sites for the controllable preparation of well-dispersed palladium nanoparticles [TP5/Pd(0) NPs]. The as-prepared TP5/Pd(0) NPs were fully characterized by X-ray photoelectron spectroscopy, transmission electron microscopy, and powder X-ray diffraction. Importantly, the ultrafine TP5/Pd(0) NPs are found to be excellent and reusable catalysts for the reduction of nitrophenols in aqueous solution.

The palladium-catalyzed asymmetric carboamination reaction is one of the most significant transformations in organic chemistry. Herein, we report the first palladium-catalyzed asymmetric alleneamination of β,γ-unsaturated hydrazones with propargylic acetates. This protocol enables the efficient installation of various multisubstituted allene groups onto dihydropyrazoles in good yields with excellent enantioselectivities. The chiral sulfinamide phosphine ligand Xu-5 exhibits highly efficient stereoselective control in this protocol. The salient features of this reaction include the readily available starting materials, a broad substrate scope, an easy scale-up, mild reaction conditions and versatile transformations., (© 2023 Wiley-VCH GmbH.)

p -TsOH-catalyzed cycloaddition of various 3-vinylindoles and (indol-2-yl)diphenylmethanols in acetonitrile gave the functionalized cyclopenta[ b ]indoles in good yields and with high diastereoselectivity via [3 + 2] cycloaddition reaction. More importantly, FeCl 3 -catalyzed annulation reaction afforded unexpected functionalized cyclohepta[1,2- b :4,5- b ']diindoles in satisfactory yields, in which a formal [4 + 3] cycloaddition and an unprecedented C3/C2 carbocation rearrangement were first confirmed by the determination of single-crystal structure.

A highly efficient palladium-catalyzed allenamide allylic alkylation of sulfenate anions under mild conditions is demonstrated. The present methodology provides a practical protocol to access various sulfoxide-containing heterocyclic compounds. The salient features of this transformation include a broad substrate scope, good functional group tolerance, easy to scale-up, and ready synthetic transformation.

We have developed an efficient protocol for the construction of polycyclic dihydrobenzofuran spirooxindole scaffolds via base promoted cascade annulation of Morita-Baylis-Hillman (MBH) carbonates of isatins with ortho -hydroxychalcones or ortho -hydroxy-β-nitrostyrenes. The complex polycyclic compounds were conveniently synthesized in satisfactory yields and with high diastereoselectivity. This protocol provides a swift and convenient approach for the assembly of diverse highly functionalized dihydrobenzofuran spirooxindoles and also features broad substrate scope, high molecular convergence, and excellent atomic economy.

Theranostics play an important role in cancer treatment due to its realized real-time tracking of therapeutic efficacy in situ. In this work, we have designed and synthesized a terpyridine-modified pillar [5]arenes ( TP5 ). By the coordination of terpyridine and Zn 2+ , the complex TP5 /Zn was obtained. Then, supramolecular amphiphile can be constructed by using host-guest complexation between a polyethylene glycol contained guest ( PM ) and TP5/Zn . Combining the fluorescence properties from the terpyridine group and the amphiphilicity from the system, the obtained TP5/Zn/PM can further be self-assembled into fluorescent particles with diameters of about 150 nm in water. The obtained particles can effectively load anti-cancer drugs and realize living cell imaging and a precise release of the drugs.

An efficient method to construct unique spiro[indoline-3,4'-pyrrolo[3,4- b ]pyridines] was successfully developed via a DABCO promoted formal [3 + 3] cycloaddition reaction of MBH carbonates of isatins with β-enamino maleimides in acetonitrile at room temperature. This reaction afforded multifunctionalized spiro[indoline-3,4'-pyrrolo[3,4- b ]pyridines] and spiro[dipyrrolo[3,4- b :3',4'- e ]pyridine-8,3'-indolines] in good yields and with lower diastereoselectivity. The relative configuration of the two diasteromers of the spiro compounds was clearly elucidated by the determination of eight single crystal structures.

Two pillar[5]arene-based [1]rotaxanes with salicylaldimine as the stopper were synthesized and characterized fully, and could be further applied in the fluorescence turn-on sensing of Zn 2+ in water.

In the presence of tetrabutylammonium bromide (TBAB), the cycloaddition reaction of phenacylmalononitriles with dialkyl but-2-ynedioates in acetonitrile at room temperature resulted in 3,3-dicyano-5-hydroxy-5-arylcyclopent-1-ene-1,2-dicarboxylates in high yields. More importantly, the DABCO-promoted domino reaction of two molecules of each phenacylmalononitrile and dialkyl but-2-ynedioate in acetonitrile at room temperature afforded unique multifunctionalized carboxamide-bridged dicyclopentenes in moderate to good yields and with high diastereoselectivity., (Copyright © 2022, Zheng et al.)

In the presence of copper sulfate, three- or four-component reactions of 2-methylindole, aromatic aldehydes and various cyclic dienophiles in refluxing toluene afforded diverse spirotetrahydrocarbazoles. This reaction is an important development of the Levy reaction by using 2-methylindole to replace ethyl indole-2-acetate and successfully provides facile access to important polysubstituted spiro[carbazole-3,3'-indolines], spiro[carbazole-2,3'-indolines], spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cycloalkanes] in satisfactory yields and with high diastereoselectivity., (Copyright © 2022, Zhan et al.)

The base promoted domino reaction of bindone ([1,2'-biindenylidene]-1',3,3'-trione) with common 1,3-dipolarophiles showed interesting molecular diversities, from which the unique spiro and fused indeno[1,2- a ]fluorine derivatives were conveniently synthesized in satisfactory yields. In the presence of a base, bindone underwent formal [3 + 3] cycloaddition with satylidene malononitriles to give dispiro[indene-2,4'-fluorene-1',3''-indoline]. It also underwent formal [4 + 2] cycloaddition with 4-arylidene-pyrazol-3-ones to give diastereoisomeric spiro[indeno[1,2- a ]fluorene-5,4'-pyrazole]. On the other hand, a triethylamine promoted reaction of three molecules of 1,3-indanediones and isatins in toluene afforded spiro[diindeno[2,1- b :2',1'- d ]anthracene-11,3'-indoline] derivatives through the domino [4 + 2] cycloaddition and ring-expansion process.

The tri( n -butyl)phosphine-catalyzed reaction of isatylidene malononitriles and bis-chalcones in chloroform at 65 °C afforded functionalized spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. On the other hand, the tri( n -butyl)phosphine-catalyzed reaction of 3-(ethoxycarbonylmethylene)oxindoles and bis-chalcones gave functionalized spiro[cyclohexane-1,3'-indolines] with different regioselectivity. Additionally, the tri( n -butyl)phosphine-promoted domino annulation reaction of isatins and ethyl isatylidene cyanoacetates produced spiro[indoline-3,2'-furan-3',3''-indolines] in satisfactory yields., (Copyright © 2022, Zheng et al.)

A DABCO-promoted annulation reaction of bindone ([1,2'-biindenylidene]-1',3,3'-trione) and 3-methyleneoxindoles showed very interesting molecular diversity under different reaction conditions. The base-promoted annulation reaction of bindone and 3-phenacylideneoxindoles in DCM at room temperature afforded spiro[indeno[1,2- a ]fluorene-5,3'-indoline] derivatives in good yields and with high diastereoselectivity. However, the similar reaction of 2-(2-oxoindolin-3-ylidene) acetates resulted in Z / E -isomeric spiro[indeno[1,2- a ]fluorene-5,3'-indolines] with diastereomeric ratios of 2:1 to 10:1. On the other hand, the DABCO-promoted annulation reaction of bindone and 3-methyleneoxindoles in acetonitrile at different temperatures selectively gave spiro[benzo[5,6]pentaleno[1,6 a - b ]naphthalene-7,3'-indoline] derivatives and complex dispiro[indoline-3,6'-[4 b ,6 a ]ethanoindeno[1,2- a ]fluorene-14',3″-indolines] in satisfactory yields.

The p -TsOH-catalyzed Diels-Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two diastereoisomers of tetrahydropyrrolo[3,4 -c ]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4 -c ]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or benzylideneacetone in acetonitrile in the presence of p -TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels-Alder reaction and sequential aromatization process., (Copyright © 2021, Fang et al.)

Functionalized spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cyclohexanes] were efficiently synthesized in satisfactory yields with high diastereoselectivity by CuSO4 catalyzed multicomponent reaction of indole-2-acetate, aromatic aldehyde and 1,3-dimethylbarbituric acid or dimedone. The reaction was finished with sequential Diels-Alder reaction of both in situ generated indole-2,3-quinodimethane and a dienophile. Additionally, the initially formed spiro[carbazole-3,5'-pyrimidines] were converted to dehydrogenated spiro[carbazole-3,5'-pyrimidines] by DDQ oxidation. The initially formed spiro[carbazole-3,1'-cyclohexanes] were converted to δ-valerolactone-substituted carbazoles by a DDQ promoted Baeyer-Villiger oxidation process.

p -TsOH catalyzed Diels-Alder reaction of 2-(1-alkylindol-3-yl)naphthalene-1,4-diones and 3-phenacylideneoxindoles showed fascinating diastereoselectivity. The reaction with the hydrated p -TsOH afforded trans -isomers of dihydrospiro[indoline-3,6'-naphtho[2,3- c ]carbazoles] as major products. Alternatively, the reaction with anhydrous p -TsOH under a Dean and Stark apparatus predominately gave cis -isomer of dihydrospiro[indoline-3,6'-naphtho[2,3- c ]carbazoles]. On the other hand, the similar p -TsOH catalyzed reaction of 2-(indol-3-yl)naphthalene-1,4-diones with 3-arylideneindolin-2-ones afforded cis / trans -isomers of dihydrospiro[indoline-3,6'-naphtho[2,3- c ]carbazoles]. Additionally, the p -TsOH catalyzed reaction of 2-(indol-3-yl)naphthalene-1,4-diones with 2-arylidene-1,3-indanediones gave the expected spiro[indene-2,6'-naphtho[2,3- c ]carbazoles] in satisfactory yields.

In the presence of copper sulfate, the three-component reaction of aromatic aldehydes, ethylindole-3-acetate and 4-arylidene-5-methyl-2-phenylpyrazol-3-ones, in refluxing toluene afforded spiro[carbazole-3,4'-pyrazoles] in good yields with high diastereoselectivity. More importantly, the similar CuSO 4 promoted the four-component reaction of two molecular aromatic aldehydes with ethylindole-3-acetate and 5-methyl-2-phenyl-pyrazol-3-one resulted in 2,4-diarylspiro[carbazole-3,4'-pyrazoles] in satisfactory yields. Additionally, CuSO 4 promoted the four-component reaction of two molecular aromatic aldehydes, ethylindole-3-acetate and 2-phenylthiazol-4-one, in refluxing toluene gave 2,4-diarylspiro[carbazole-3,4'-thiazoles] with diastereomeric ratios in the range of 3:1 to 20:1.

A simple InBr 3 -catalyzed domino reaction of indoles, phenylacetylenes, and various 3-methyleneoxindolines in toluene is described. This reaction not only provided a convenient synthetic protocol for polysubstituted tetrahydrospiro[carbazole-1,3'-indolines] in good yields but also gave completely different diastereoisomers of the tetrahydrospiro[carbazole-1,3'-indolines] to that of the previously reported TfOH-catalyzed one-pot reaction of indoles, acetophenones, and 3-methyleneoxindolines. Additionally, the InBr 3 -catalyzed reaction of the initially prepared 1,1'-bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also gave the corresponding tetrahydrospiro[carbazole-1,3'-indolines] in good yields and with excellent diastereoselectivity. The reaction mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels-Alder reaction, and the Lewis acid controlled diastereoisomerization process.

The three-component reaction of α , β -unsaturated N -arylaldimines, dialkyl but-2-ynedioates, and 2-arylidene Meldrum acids in DCM at room temperature gave mixtures of cis / trans -11-aryl-7-styryl-2,4-dioxa-8-azaspiro[5.5]undec-9-enes in satisfactory yields. The similar three-component reaction with 2-arylidene- N , N '-dimethylbarbituric acids afforded cis -11-phenyl-7-styryl-2,4,8-triazaspiro[5.5]undec-9-enes as major products. On the other hand, the three-component reaction of N -arylaldimines, dialkyl but-2-ynedioates, and 2-arylidene Meldrum acids or 2-arylidene- N , N '-dimethylbarbituric acids afforded cis / trans- isomeric spirocompounds in satisfactory yields with high diastereoselectivity. This domino [2+2+2] cycloaddition reaction proceeded with sequential nucleophilic addition of N -arylaldimine to an electron-deficient alkyne, Michael addition, and annulation process. The stereochemistry of all cis / trans isomeric spirocompounds was clearly elucidated by the determination of 33 single-crystal structures. The diastereoselectivity of the three-component reaction was correlated by DFT calculations.

A triethylamine-promoted domino reaction of three molecular 1,3-indanediones with various 3-methyleneoxindoles in refluxing ethanol has been developed. Series of novel polycyclic triindanone-fused spiro[bicyclo[2.2.2]octane-2,3'-indoline] derivatives were successfully synthesized in satisfactory yields with high diastereoselectivity. This domino reaction was accomplished with in situ generation of active cyclic dienes by base-promoted cyclotrimerization or cyclotetramerization of 1,3-indanediones and sequential Diels-Alder reaction of active cyclic dienes with dienophilic 3-methyleneoxindoles.

The three-component reaction of alkyl 2-(benzo[ b ][1,4]thiazin-3-ylidene)acetates, isatins, and 1,3-indanedione (1,3-cyclopentanedione) in ethanol in the presence of acetic acid conveniently afforded spiro[indeno[1,2- b ]phenothiazine-6,3'-indolines] or spiro[cyclopenta[ b ]phenothiazine-4,3'-indolines] in good yields and with high diastereoselectivity. More interestingly, a similar three-component reaction with 4-hydroxychromen-2-one resulted in the unexpected polycyclic spiro[benzo[ b ]chromeno[3',4':5,6]pyrano[2,3- e ][1,4]thiazine-7,3'-indolines] in satisfactory yields. A plausible reaction mechanism was rationally proposed for formation of different kinds of the spiro compounds, and the stereochemistries of the various spiro compounds were clearly elucidated.

Triethylamine promoted the pseudo-five-component reaction of aromatic aldehyde with four molecules of 1,3-indanediones in refluxing ethanol to give unique polycyclic bicyclo[2.2.2]octane derivatives containing bridged- and spiro-indanone scaffolds in good yields. The mechanistic studies supported that the reaction included base-catalyzed cyclotrimerization of 1,3-indanedione to give an active cyclic diene and the sequential Diels-Alder reaction with in situ generated 2-arylidene-1,3-indanediones as electron-deficient dienophiles. On the other hand, the pseudo-four-component reaction of salicylaldehyde with 1,3-indanedione afforded the dibenzo[ b , g ]indeno[1',2':3,4]fluoreno[1,2- d ]oxonines in high yields. This reaction clearly demonstrated the high efficiency, molecular convergence, atom-economy, and impressive selectivity of multicomponent reactions.

The CuSO4 catalyzed three-component reaction of indole-2-acetate, aromatic aldehydes and 3-methyleneoxindoles in toluene at 130 °C afforded polysubstituted spiro[carbazole-3,3'-indolines] in good yields and with high diastereoselectivity. When isatylidene malononitriles were used as dienophiles, regio-isomeric spiro[carbazole-2,3'-indolines] were selectively obtained. A similar three-component reaction with 2-arylidene-1,3-indanediones resulted in polysubstituted spiro[carbazole-3,2'-indenes] in satisfactory yields and with high diastereoselectivity. The stereochemistry of the diastereoisomers of the spiro compounds was clearly elucidated by analysis of NMR spectra and determination of fourteen single crystal structures. The reaction mechanism included formation of reactive 2,3-dimethyleneindoline and a sequential Diels-Alder reaction.

An efficient synthetic protocol for novel indeno[1,2-a]fluorene derivatives was successfully developed by the base promoted domino reaction of 1,3-indanedione with 3-arylideneindolin-2-ones. The domino reaction in different solvents selectively gave carbamato- or amino-substituted indeno[1,2-a]fluorene in satisfactory yields. Additionally, a similar domino reaction of 1,3-indanediones with chalcones also gave polysubstituted indeno[1,2-a]fluorenes in high yields. The reaction mechanism is believed to proceed with base-promoted dimerization of 1,3-indanedione, Michael condensation, annulation, ring-opening of indolin-2-one and aromatization process.

The acetic acid catalyzed three-component reaction of pyrrolidine, aromatic aldehydes, and 3-arylideneoxindolin-2-ones in refluxing toluene afforded functionalized 7'-arylidenespiro[indoline-3,1'-pyrrolizines] in good yields and with high diastereoselectivity. The similar three-component reaction with 2-arylidene-1,3-indanediones also gave 7'-arylidenespiro[indene-2,1'-pyrrolizines] in good yields. However, the reaction with 3-phenacylideneoxindoles resulted in a mixture of spiro[indoline-3,1'-pyrrolizines] and 7'-arylidene-substituted spirooxindoles in moderate yields. The reaction mechanism included generation of azomethine ylides, β-C-H functionalization of pyrrolidine, and sequential [3 + 2] cycloaddition. The obtained spirooxindole derivatives were investigated by in vitro evaluation against mouse colon cancer cells CT26 and human liver cancer cells HepG2 by MTT assay.

The one-pot base-promoted cascade double [3 + 2] cycloaddition reaction of N-cyanomethylisoquinolinium chloride with (E)-3-arylideneindolin-2-ones and (E)-N-hydroxybenzimidoyl chloride afforded novel polycyclic spiro[indoline-3,8'-isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinolines] in good yields and with high diastereoselectivity. When 4-arylidenepyrazol-3-ones, 2-arylidene-1,3-indanediones and arylidenemalononitriles were employed in the reaction, the corresponding spiro[isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline-8,4'-pyrazole], spiro[indene-2,8'-isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline], and isoxazolo[5,4-c]pyrrolo[2,1-a]isoquinoline derivatives were also prepared in good yields and with high diastereoselectivty. The relative configurations of the polycyclic spiro compounds were clearly elucidated by determination of fifteen single crystal structures.

The catalyst-free domino reaction of α,β-unsaturated N -alkyl or N -arylaldimines with two molecules of 2-arylidene-1,3-indanediones in dry acetonitrile resulted in polysubstituted spiro[indene-2,3'-indeno[2',1':5,6]pyrano[2,3- b ]pyridines] in moderate to good yields and with high diastereoselectivity. The reaction mechanism included sequential aza/oxa-Diels-Alder reactions via both endo-transition states. On the other hand, the catalyst-free domino reaction of α,β-unsaturated N -arylaldimines with 2,2'-(arylmethylene)bis(1,3-indenediones) afforded the mixed diastereoisomeric dispiro[indene-2,1'-cyclohexane-3',2″-indene] derivatives in satisfactory yields. The reaction mechanism of this formal [3 + 3] cycloaddition was believed to proceed with sequential nucleophilic 1,4-/1,2-additions., Competing Interests: The authors declare no competing financial interest.

The three-component reaction of 1,3-indanedione and N-alkylisatins with two molecular N-phenacylpyridinium salts in dry acetonitrile in the presence of triethylamine resulted in unique functionalized spiro[indoline-3,4'-naphtho[1,2-b]furan] derivatives in good yields, which were successfully converted to spiro[indoline-3,2'-naphthalen]-4'-yl acetate derivatives by acylation with acetyl chloride in methylene dichloride and alkoxy-substituted spiro[benzo[h]chromene-5,3'-indolines] by acid-catalyzed etherification reaction in alcohol. The reaction mechanism involved the sequential cycloaddition of the in situ-generated pyridinium ylide to dipolarophilic enone, ring-opening of 1,3-indanedione, and selective annulation.

The acid-promoted three-component reaction of o-aminophenol or 2-aminoethanol with dialkyl acetylenedicarboxylate and 3-phenacylideneoxindolines in refluxing acetonitrile afforded functionalized oxindolinyl-substituted benzo[b]pyrrolo[1,2-d][1,4]oxazine or pyrrolo-[2,1-c][1,4]oxazine derivatives in good yields. However, using o-phenylenediamine only resulted in oxindolinyl-substituted 3,4-dihydroquinoxaline derivatives.

The multicomponent reaction of l-proline, isatins, and excess of methyl propiolates in methanol unexpectedly afforded 2-(oxoindolin-3-ylidene)propylidene)pyrrolidin-1-yl)acrylates in good yields, and the products subsequently converted to unique nine-membered pyrrolo[1',2':1,9]azonino[6,5,4- cd]indoles in the presence of p-TsOH. Furthermore, the multicomponent reaction of l-proline, N-benzylisatins, and excess alkyl propiolates in refluxing chloroform unprecedentedly resulted in eight-membered azocino[1,2- a]benzo[ c][1,5]diazocines as the main product. The molecular structures of the polyheterocyclic compounds were confirmed by determination of 19 single crystal structures. The reaction mechanism was believed to contain the sequential 1,3-dipolar cycloaddition, addition of cyclic tertiary amine to excess of propiolate, and fascinating ring opening as well as rearrangement process. The N-substituent on isatins played a critical role in the different reaction patterns.