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A base-promoted formal (2+1) cycloaddition of benzofuran-derived oxadienes with bromomalonates was established that afforded benzofuranone-based spirocyclopropanes in generally good yields (up to 98%) and high diastereoselectivities (up to 91:9 dr). This reaction is the first highly diastereoselective formal (2+1) cycloaddition of benzofuran-derived oxadienes, and will contribute to the chemistry of these compounds. In addition, this approach provides an atom-economic and useful protocol for constructing benzofuranone-based spiro skeletons.

Enantioenriched indole derivatives are widely found in natural products, pharmaceuticals and bioactive compounds. Therefore, developing efficient methods for the synthesis of enantioenriched indole derivatives has become an important goal in the community of organic chemistry. To this end, chemists have designed and developed a variety of indole-containing platform molecules and their related catalytic asymmetric reactions. Among these approaches, vinylindoles have proved to be versatile platform molecules for accessing enantioenriched indole derivatives via catalytic asymmetric reactions, especially organocatalytic asymmetric reactions. Based on this approach, a plethora of chiral indole derivatives have been synthesized with optical purity and structural complexity. This review summarizes advances in vinylindole-based organocatalytic asymmetric reactions since 2008 and includes the applications of some methodologies in the total synthesis of natural products. In addition, this review points out the remaining challenges in this research area to be confronted by organic chemists, which will shed light on the future development of this area.

Catalytic asymmetric [2 + 4] cycloadditions of 3-vinylindoles with ortho-quinone methides and their precursors were carried out in the presence of chiral phosphoric acid to afford a series of indole-containing chroman derivatives with structural diversity in overall high yields (up to 98%), good diastereoselectivities (up to 93:7 dr) and moderate to excellent enantioselectivities (up to 98% ee). This approach not only enriches the chemistry of catalytic asymmetric cycloadditions involving 3-vinylindoles but is also useful for synthesizing chiral chroman derivatives.

A catalytic asymmetric (4 + 2) cyclization of ortho-hydroxyphenyl-substituted para-quinone methide derivatives with 3-vinylindoles has been established in the presence of chiral phosphoric acid, which provides a series of chiral chroman derivatives bearing an indole moiety in generally high yields (up to 97%), and with good enantioselectivities (up to 90% ee) and moderate to good diastereoselectivities (up to 95 : 5 dr). This reaction has not only fulfilled the need of developing catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with electron-rich alkenes, but also provided a useful method for constructing chiral chroman scaffolds.

A diastereo- and enantioselective construction of biologically important chiral 1,3-dioxolochroman frameworks has been established via chiral phosphoric acid (CPA)-catalyzed asymmetric [4+2] cycloaddition of ortho-quinone methides with 3-methyl-2-vinylindoles. By using this approach, a series of indole-based chiral 1,3-dioxolochromans were synthesized with structural diversity in generally good yields, excellent diastereoselectivities and high enantioselectivities (up to 98% yields, >95:5 dr, 97% ee). The evaluation on the cytotoxic activity of some selected products indicated that this class of chiral 1,3-dioxolochroman derivatives had some extent of anti-cancer activity. This reaction not only provides an efficient synthetic method for accessing chiral 1,3-dioxolochroman derivatives with structural diversity and optical purity but also will enrich the research contents of catalytic asymmetric [4+2] cycloadditions involving ortho-quinone methides. In addition, the bioassay of these compounds will cast a light on discovering useful bioactivities of chiral 1,3-dioxolochroman derivatives, which will be helpful for finding lead compounds.

An efficient approach for the synthesis of chromene derivatives from vinyl o-quinone methides was established via a Brønsted acid catalyzed electrocyclization. By using this methodology, a series of structurally diversified chromenes was synthesized in a highly atom-economic and environmentally benign manner with generally good to excellent yields (up to 98% yield). This reaction will not only provide an efficient method for the construction of chromene scaffolds, but also enrich the research area of o-quinone methides.

o-Quinone methides generated at high temperature under organocatalysis from commonly used o-hydroxystyrenes undergo enantioselective cyclization with dimedone-derived enaminones, to form biologically important tetrahydroxanthenes in high yields and good enantioselectivities (up to 88% yield, 95:5 er). The reaction proceeds in chlorobenzene in the presence of a chiral phosphoric acid (CPA) at 110 °C. The reaction scope with regard to various ring-substituted o-hydro­xy­styrenes and various N-aryl-substituted enaminones was investigated. In addition, this reaction also provided an efficient method for constructing chiral tetrahydroxanthene scaffolds.

A series of pyrano-fused pyrazolo[3,4-b]pyridine derivatives with an aryl group presenting the 2-position of the pyridine nucleus have been synthesized by microwave-assisted three-component reactions of aldehydes, tetrahydropyran-4-one, and 3-methyl-1-phenyl-1H-pyrazol-5-amine in HOAc. This method is very efficient because of short reaction times and easy work-up, and it provides an efficient and promising synthetic strategy for the construction of the tricyclic pyrano-fused pyrazolo[3,4-b]pyridine skeleton.

A new domino strategy for efficient synthesis of highly functionalized quinoxaline derivatives via [4 + 2] heterocyclization involving ring-opening of oxirane process has been developed. The reaction promoted by Cs2CO3 was easy to perform in a simple operation from common and inexpensive starting materials. The bisfunctionalization of quinoxaline framework including C2 benzylation and C3 arylation was readily achieved in domino fashion that involved the cleavage of three C–O bonds of 1,3-diaryl-2,3-epoxypropan-1-one.

The scalable title reaction between 2-arylidene-2-aryloxazol-5(4H)-ones and cyclohexane-1,3-diones to biologically important hexahydrocoumarins is described.

Concise and efficient domino [3+2+1] heterocyclization of isothiocyanates with aryl amidines has been established for the synthesis of 1,3,5-triazine derivatives. The multicomponent domino reaction (MDR, AB 2 type) is easy to perform simply by mixing inexpensive isothiocyanates and aryl amidines in the presence of NaOH under microwave heating. The present synthesis shows attractive properties such as concise one-pot conditions, short reaction periods (15–24 min), and easy purifications. The resulting 1,3,5-triazine derivatives are important structural motifs in organic and medicinal research.

A series of new poly-functionalized indole derivatives were synthesized via domino reactions of alloxan monohydrate and N-aryl substituted enaminones in HOAc at room temperature. The direct C3-bisfunctionalization of indole ring was achieved in a one-pot operation. The reaction is easy to perform simply by mixing common reactants in acetic acid. The reaction proceeds at fast rates and can be finished within 24 min, which makes workup convenient to give good to excellent chemical yields.

A series of new poly-functionalized dihydroquinoline derivatives (26 examples) were synthesized via three-component reactions of aldehydes (1 equiv) and 1-arylethylidenemalononitriles (2 equiv) in ethylene glycol using NaOH as a base promoter under microwave irradiation. During these reaction processes, the domino construction of dihydroquinoline skeleton with concomitant formation of two new cycles was readily achieved in a one-pot operation and in an intermolecular manner.

The first catalytic asymmetric construction of the biologically important hexahydrocoumarin scaffold has been established, which takes advantage of chiral thiourea-tertiary amine-catalyzed enantioselective transformations. Besides, this reaction also realized the first catalytic asymmetric [3 + 3] cyclization of 4-arylidene-2-aryloxazol-5(4H)-ones with cyclohexane-1,3-diones, which afforded structurally diverse 3-aminohexahydrocoumarin derivatives in excellent diastereoselectivities and high enantioselectivities (all95:5 dr, up to 96:4 er). The investigation on the activation mode suggested that the chiral thiourea-tertiary amine catalyst simultaneously activated the two substrates via hydrogen-bonding interaction. Moreover, this reaction could be applied to a large scale synthesis of enantioenriched hexahydrocoumarin. This approach will not only provide an efficient method for the construction of the chiral hexahydrocoumarin scaffold but also enrich the research areas of asymmetric organocatalysis and catalytic enantioselective [3 + 3] cyclizations.

Bronsted acid-promoted divergent approaches for the synthesis of multi-functionalized fused pyrroles with different substituted patterns (44 examples) have been established. The divergent pathways were controlled by varying the charging sequence to give a series of new fused pyrroles selectively. The direct C(sp3)S bond formation was achieved for the two-step, one-pot reaction.

New three-component domino reaction providing divergent approaches to multifunctionalized fused pyrroles with different substituted patterns have been established (40 examples). The direct C(sp(3))-N bond formation was achieved through intermolecular allylic amination in a one-pot operation, and N-arylation of amines was realized by varying N-amino acid enaminones. The reaction is easy to perform simply by mixing three common reactants in acetic acid under microwave heating. The reaction proceeds at fast rates and can be finished within 30 min, which makes workup convenient to give good chemical yields.

An efficient dimedone-catalyzed synthesis of highly functionalized thiazol-2-yl substituted E-acrylonitrile derivatives has been established through two-step reaction of α-thiocyanate ketones with malononitrile and amines. The α-thiocyanate ketones were subjected with malononitrile to provide thiazol-2-ylidenemalononitrile derivatives, followed with various amines in the present of dimedone to yield the final thiazol-2-yl substituted acrylonitrile derivatives.

A series of new functionalized thiopyrano-, pyrano[4,3-d]pyrimidine derivatives with benzyl group residing in 8-position of fused pyrimidine nucleus were synthesized through multicomponent reactions of aromatic aldehydes, tetrahydrothiopyran-4-one(tetrahydropyran-4-one), and aryl amidines using t-BuOK as a base under microwave heating. The procedure is facile, avoiding time-consuming and costly syntheses, tedious work-up, and purifications of precursors as well as protection/deprotection of functional groups. This method is very efficient due to short reaction times and easy work up and provides a four-component strategy for the construction of the thiopyrano-, and pyrano[4,3-d] pyrimidine skeletons.

A tandem one-pot synthesis of polysubstituted 1,3-thiazines has been developed by reacting with cyanoacetamide and isothiocyanate derivatives to give rise to 2-cyano-3-mercaptoacrylamides, which are trapped in situ by various aldehydes or diversely substituted ketones through intermolecular cyclization, providing polysubstituted 1,3-thiazine derivatives in short reaction times with good to excellent yields. The salient features of this novel protocol are operational simplicity, accessing the desired products from the readily available starting materials and easy of product isolation and may find wide spread applications in medicinal chemistry.

A new domino strategy for an efficient synthesis of highly functionalized quinoxaline derivatives (III) is developed using a [4 + 2] heterocyclization procedure involving a ring-opening of oxirane.

A series of pyrano-fused pyrazolo[3,4-b]pyridine derivatives with an aryl group presenting the 2-position of the pyridine nucleus have been synthesized by microwave-assisted three-component reactions of aldehydes, tetrahydropyran-4-one, and 3-methyl-1-phenyl-1H-pyrazol-5-amine in HOAc. This method is very efficient because of short reaction times and easy work-up, and it provides an efficient and promising synthetic strategy for the construction of the tricyclic pyrano-fused pyrazolo[3,4-b]pyridine skeleton.

The chiral phosphoric acid catalyzed asymmetric Diels–Alder reactions of 2-vinylindoles with methyleneindolinones have been established, which efficiently construct the spiro[tetrahydrocarbazole-3,3′-oxindole] architecture with one quaternary and three contiguous stereogenic centers in high yields (up to 99%) and excellent stereoselectivities (up to >95:5 dr, 97% ee). This reaction not only provides an efficient strategy to access enantioenriched spiro[tetrahydrocarbazole-3,3′-oxindoles] based on hydrogen-bonding activation mode but also supplies successful examples of catalytic asymmetric Diels–Alder reactions for constructing complex spiro-frameworks with optical purity.

A new iodonium ylide-based three-component reaction for the synthesis of highly functionalized 2-spirosubstituted dihydrofurans starting from readily available common reactants has been developed under microwave irradiation. The procedure is facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors as well as protection/deprotection of functional groups. This method is very efficient because of short reaction times and easy work-up and provides an efficient strategy for the construction of the polysubstituted spiro dihydrofuran skeleton.

Highly selective four-component domino multicyclizations for the synthesis of new fused acridines and azaheterocyclic skeletons have been established by mixing common reactants in isobutyric acid under microwave irradiation. The reactions proceeded at fast rates and were conducted to completion within 20–30 min. Up to seven new chemical bonds, four rings, and four stereocenters were assembled in a convenient one-pot operation. The resulting hexacyclic and pentacyclic fused acridines and their stereochemistry have been fully characterized and determined by X-ray structural analysis.

A convenient one-pot procedure renders possible the preparation of triazine derivatives (24 examples) in a short time.

Highly selective four-component domino multicyclizations for the synthesis of new fused acridines and azaheterocyclic skeletons have been established by mixing common reactants in isobutyric acid under microwave irradiation. The reactions proceeded at fast rates and were conducted to completion within 20–30 min. Up to seven new chemical bonds, four rings, and four stereocenters were assembled in a convenient one-pot operation. The resulting hexacyclic and pentacyclic fused acridines and their stereochemistry have been fully characterized and determined by X-ray structural analysis.

The construction of C3-difunctionalized indoles (III) is readily achieved through metal-free ring opening of alloxan monohydrate (II) with enaminones (I).

Acetic acid is used as a solvent and a Broensted acid to promote the reaction of arylglyoxals, enaminones and mercaptans.

A mild, fast, excellent atom-economical, and convenient one-pot method for the synthesis of the title compound is described.

The domino construction of the desired heterocyclic scaffold (26 examples) proceeds with concomitant formation of 2 new cycles in a one-pot operation.

AcOH-mediated treatment of the enaminones (I) and (V) with arylglyoxal monohydrate and aromatic amines allows a new and efficient access to 7-aminated dihydroindolones of type (IV) and (VI).

The dimedone-mediated addition of amines to a cyano group of (I) proceeds with high chemoselectivity and a broad scope of substrates can be employed.

The reaction of equimolar amounts of aldehydes bearing electron-donating aryl groups, hydrazines and esters (II) results in formation of pyrazolones.

A novel pseudo four-component reaction of 4-pyranones or thiones with aromatic aldehydes and arylamidines is established to provide the anellated pyrimidines regioselectively.

A series of new poly-functionalized fused naphthyridine derivatives were synthesized via a three-component reaction of aldehyde, 2-aminoprop-1-ene-1,1,3-tricarbonitrile and enaminone in EtOH using EtONa as a base. During these reaction processes, the domino construction of fused naphthyridine skeleton with concomitant formation of two new pyridine rings was readily achieved via base promoted three-component reactions in a one-pot operation. The procedures are facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors.

A tandem one-pot synthesis of polysubstituted 1,3-thiazines has been developed by reacting with cyanoacetamide and isothiocyanate derivatives to give rise to 2-cyano-3-mercaptoacrylamides, which are trapped in situ by various aldehydes or diversely substituted ketones through intermolecular cyclization, providing polysubstituted 1,3-thiazine derivatives in short reaction times with good to excellent yields. The salient features of this novel protocol are operational simplicity, accessing the desired products from the readily available starting materials and easy of product isolation and may find wide spread applications in medicinal chemistry.

A new [5 + 1] rearrangement–annulation for the regioselective formation of polyfunctionalized [1,6]naphthyridines is described. The new construction of a pyridin-2(1H)-one skeleton and its alkylation on the pyridin-2(1H)-one unit were readily achieved through a novel sequential [4 + 2] cyclization–ring opening–intramolecular cyclization–re-cyclization–elimination of urea process.