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An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-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(1H)-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.

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.

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.

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.

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.

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.

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.

A new DBU-catalyzed formal [4 ​+ ​2] cycloaddition between ortho-hydroxyphenyl-substituted para-quinone methides and electron-deficient dienophiles including 3-methyleneoxindoles and 2-aryldeneindene-1,3-diones was established. A wide range of functionalized spiro[chromane-3,3′-indolines] and spiro[chromane-3,2′-indenes] were successfully synthesized in good yields and with high diastereoselectivity. The features of the reaction included readily available substrates, mild reaction conditions, convenient methodology and good functional group tolerance.

An uncommon aza-Diels-Alder reaction of electron-deficient azoalkenes and electron-deficient 3-phenacylideneoxindoles was successfully developed for convenient construction of the heterocyclic spirooxindoles. The aza-Diels-Alder reaction of azoalkenes, which were in situ generated from base dehydrohalogenation of α-halogeno N-acylhydrazones, with 3-methyleneoxindoles afforded functionalized spiro[indoline-3,3′-pyridazin]-2-ones in good yields and with high diastereoselectivity. Under same reaction conditions, the base promoted reaction of α-halogeno N-acylhydrazones and 3-aryliminoindolin-2-ones in DCM at room temperature resulted in functionalized spiro[indoline-3,3'-[1,2,4]triazin]-2-ones 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.

An efficient method for the synthesis of deuterated homologation of boronate esters was developed. This discovery uses robust deuterated agent 5-(methyl-d3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT) as d2-methylene source. Mechanistically, base promoted deprotonation of DMTT to generate d2-sulfur-methylene ylide intermediate, which attack the boron atom of boronic ester and followed by 1,2-migration to afford the deuterated boronic homologues. The developed protocol provides a unique approach to achieve one-carbon growth under the practical mild conditions.

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 Zn2+, 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.

The pillar[5]arene mono- and di(oxyalkoxy)benzoic acids were successfully prepared in high yields by sequential alkylation of ω-bromoalkoxy-substituted pillar[5]arenes with methyl or ethyl p-hydroxybenzoate followed by a hydrolytic reaction under basic conditions. Under catalysis of HOBt/EDCl, the amidation reaction of pillar[5]arene mono(oxybutoxy)benzoic acid with monoamido-functionalized pillar[5]arenes afforded diamido-bridged bis-pillar[5]arenes. 1H NMR and 2D NOESY spectra clearly indicated that [1]rotaxanes were formed by insertion of longer diaminoalkylene unit into the cavity of one pillar[5]arene with another pillar[5]arene acting as a stopper. The similar catalysed amidation reaction of pillar[5]arene di(oxybutoxy)benzoic acid with monoamido-functionalized pillar[5]arenes resulted in the diamido-bridged tris-pillar[5]arenes, which successfully form the unique bis-[1]rotaxanes bearing longer than diaminopropylene diamido bridges.

The one-pot four-component reaction of benzohydrazide (2-picolinohydrazide), acetylenedicarboxylate, isatins and malononitrile (ethyl cyanoacetate) with triethylamine as base catalyst afforded functionalized 1-benzamidospiro[indoline-3,4'-pyridines] in good yields. 1H NMR spectra indicated that an equilibrium of cis/trans-conformations exist in the obtained products.

The four-component reaction of 2-aminobenzothiazole, aromatic aldehydes, acetylenedicarboxylate and piperidine or pyrrolidine in ethanol afforded the functionalized 2-pyrrolidinones containing both benzothiazolyl and piperidinyl (or pyrrolidinyl) units in good yields. On the other hand, the similar four-component reactions resulted in the functionalized morpholinium or piperidinium 2-pyrrolidinon-3-olates in the presence of p-toluenesulfonic acid.

In the presence of triethylamine as catalyst, the one-pot four-component reactions of arylamines, methyl propiolate, isatin and malononitrile afforded the functionalized spiro[indoline-3,4’-pyridine] derivatives in good yields. Similar reactions with ethyl cyanoacetate successfully afforded the functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] as the main products according to the structures of the arylamines and other primary amines.

A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N-alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles.

A fast and convenient protocol for the synthesis of novel spiro[dihydropyridine-oxindole] derivatives in satisfactory yields was developed by the three-component reactions of arylamine, isatin and cyclopentane-1,3-dione in acetic acid at room temperature. On the other hand the condensation of isatin with two equivalents of cyclopentane-1,3-dione gave 3,3-bis(2-hydroxy-5-oxo-cyclopent-1-enyl)oxindole in high yields. The reaction mechanism and substrate scope of this novel reaction is briefly discussed.

In the presence of p-toluenesulfonic acid as catalyst the domino reaction of arylamines, methyl propiolates and aromatic aldehydes in ethanol proceeded smoothly to give polysubstituted 1,2,3,4-tetrahydroquinolines in moderate yields. The reaction is believed to involve the Povarov reaction of in situ generated β-enamino ester with the in situ formed aromatic imine.