Six multicomponent reactions were developed by using aldo-X reagents and α-oxoketene dithioacetals with indoles or amines as substrates, which can be used to prepare many heterocycles, such as dihydrocoumarins, quinolines, furans and pyrroles, in a straightforward way. A combination of two bifunctional aldo-X reagents and α-oxoketene dithioacetals is the key to make the discovery of these multicomponent reactions possible because these reagents have a minimum of two reactive sites, which enable different substrates to be assembled together in various manners.

We show that the coating of choline chloride on silica-supported AlCl₃ allows the dehydration of carbohydrates to successfully proceed in low boiling point organic solvents. The concept is based on the in situ formation of a deep eutectic liquid phase on the catalyst surface, thus facilitating the interaction between the solid catalyst and insoluble carbohydrate.

Lignosulfonate (LS) is an organic waste generated as a byproduct of the cooking process in sulfite pulping in the manufacture of paper. In this paper, LS was used as an anionic supporting material for immobilizing cationic species, which can then be used as heterogeneous catalysts in some organic transformations. With this strategy, three lignin-supported catalysts were prepared including 1) lignin-SO₃Sc(OTf)₂, 2) lignin-SO₃Cu(OTf), and 3) lignin-IL@NH₂ (IL=ionic liquid). These solid materials were then examined in many organic transformations. It was finally found that, compared with its homogeneous counterpart as well as some other solid catalysts that are prepared by using different supports with the same metal or catalytically active species, the lignin-supported catalysts showed better performance in these reactions not only in terms of activity but also with regard to recyclability.

A sulfonyl-containing ammonium-based Brønsted acid ionic liquid was prepared and used as a liquid heterogeneous catalyst for organic reactions. The unique macroscopic phase heterogeneity of the IL in the reaction system not only ensures an excellent catalytic activity of the IL catalyst but also avoids the use of organic reaction solvents. The catalyst system is applicable for a wide range of reactions.

Acid-catalyzed Friedel–Crafts alkylation of 1,3-dicarbonyl compounds with electrophilic alcohols, is known to be an effective CC bond forming reaction. However, until now, this reaction has not been amenable for α-alkylation of aryl methyl ketones because of the notoriously low nucleophilicities of these compounds. Therefore, α-alkylation of aryl methyl ketone relies on precious metal catalysts and also, the use of primary alcohols is mandatory. In this study, we found that a system composed of a Fe(OTf)₃ catalyst and chlorobenzene solvent is sufficient to promote the title Friedel–Crafts reaction by using benzhydrols as electrophiles. 3,4-Dihydro-9-(2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-xanthen-1(2 H)-one was also applicable as an electrophile in this type of benzylation reaction. On the basis of this result, a three-component reaction of salicylaldehyde, dimedone, and aryl methyl ketone was also developed, and this provided an efficient way for the synthesis of densely substituted 4H-chromene derivatives.

A mixture of two bio-based chemicals, meglumine and gluconic acid aqueous solution (GAAS, 50 wt%), was demonstrated to be a task-specific bio-based solvent for performing the hydroxymethylation of β-ketosulfones with formaldehyde. The formed hydroxymethylation product could further react with a nucleophile, which allowed us to develop some one-pot, stepwise, three-component reactions of β-ketosulfones and formaldehyde in this binary mixture. Particularly, a one-pot, two-step, sequential four-component reaction of α-bromo ketone, sodium benzenesulfinate, thiophenol and formaldehyde was also developed. These results not only demonstrate that it is possible to develop a new bio-based system by mixing two or more bio-based chemicals together, but also confer us a convenient means for controlling the selectivity of some multicomponent reactions of formaldehyde. Because GAAS and meglumine are both highly hydrophilic, the mixed solvent system could thus be recovered after extraction of organic products. In a three-component reaction of β-ketosulfone, paraformaldehyde and α-methylstyrene, the GAAS/meglumine system could be reused at least four times without significant loss of activity.

The selectivity of a three-component electrophilic reaction of an aldehyde with dimedone and another carbon-based nucleophile could be improved by a reversible alkylation procedure, which involves formation, breaking and regeneration of CC bonds. In the presence of iron(III) chloride and triphenylphosphine, an analogous CC bond breaking can be observed in the reaction of 2,3,4,9-tetrahydro-9-(2-hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-3,3-dimethyl-1H-xanthen-1-one, in which the fragment of dimedone was replaced by a carbon-based nucleophile. Inspired by this observation, some three-component reactions of salicyldehyde and dimedone were successfully developed by using iron(III) chloride and triphenylphosphine (PPh₃) as catalyst. PPh₃ plays the role of hydrogen bond acceptor, which confers a good flexibility of the substrate by weakening the intramolecular hydrogen bond, allowing thus an easy interaction of the substrate with iron(III) chloride catalyst.

Catalysis by manganese chloride tetrahydrate was found to be effective for the selective transformation of indoles, with which the desired acid-catalyzed reaction could be promoted and, at the same time, a side reaction that also needs assistance of acid, the electrophilic reaction of indole with the co-existing keto carbonyl group, does not occur. Some acid-catalyzed reactions, such as the ring-opening reaction of 2-alkoxy-3,4-dihydropyran with indole, and transesterification of β-keto ester with an alcohol that contains a C-3 unsubstituted indole fragment, could be performed smoothly by using manganese chloride as catalyst. A new multicomponent reaction of indole, 3,4-dihydropyran and β-keto ester was also developed with catalysis by manganese chloride.

Nitromethane, a volatile and toxic organic compound, is commonly used as solvent for organic and catalytic reactions. In order to find an alternative for this specific nitro-containing organic solvent, the performance of some nitro-functionalized imidazolium salts such as 1-methyl-3-(4-nitrobenzyl)imidazolium hexafluorophosphate, 1-methyl-3-(4-nitrobenzyl)imidazolium tetrafluoroborate, 1-methyl-3-(4-nitrobenzyl)imidazolium bis(trifluoromethanesulfonyl)amide and 1,2-dimethyl-3-(4- nitrobenzyl)imidazolium hexafluorophosphate, was examined in some reactions including trimethylsilylation of alcohols with hexamethyldisilazane, ring-opening reactions of 2-aryl-3,4-dihydropyrans with thiophenols or thiols, and a copper- mediated oxidative coupling of alkynes. As expected, these imidazolium salts can indeed replace nitromethane in these reactions. Particularly, the imidazolium salt along with the metal catalyst, if involved, can be easily recovered and reused without significant loss of activity. The use of these nitro-functionalized imidazolium salts as alternative solvents for nitromethane not only confers a green aspect to the reaction system, but also facilitates a rational design of a catalytic system with the concept of green chemistry.

Glycerol has proved to be an effective promoting medium for many multicomponent reactions of 1,3-cyclohexanediones and formaldehyde. Styrenes, amines, 2-naphthol, 4-hydroxy-6-methyl-2-pyrone and 4-hydroxy-1-methyl-2-quinolone could easily react with 1,3-cyclohexanediones and paraformaldehyde in glycerol under catalyst-free conditions to afford a variety of complex skeletons in fair to excellent yields. In these reactions, glycerol not only showed a significant promoting effect on the reaction yields but also endowed the reaction system with many typical properties of green chemistry, such as cheap, renewable, recyclable and biodegradable solvent, good safety and easy separation of product. The promoting effect of glycerol for the three-component reaction of styrene, dimedone and paraformaldehyde could be attributed to a restricted formation of the methylene intermediate in glycerol. During the reaction, a physical shell, which is mainly composed of a by-product generated in the beginning of the reaction, might be formed in the surface of paraformaldehyde and plays a key role in controlling the formation of the intermediate by means of restricting the decomposition of paraformaldehyde.

In this paper, a basic method to access new multicomponent reactions (MCRs) is reported. The mechanism of these MCRs is based on the trapping of methylene intermediates, formed in situ by reaction of formaldehyde with electron-rich carbons, with alkene, thiol or indole derivatives. According to our strategy, a wide range of valuable skeletons has been obtained in a one-pot reaction, thus allowing a minimization of waste, cost and labor. The presented methodology exhibits a broad substrate scope and electron-rich carbons in the α-position of a hydroxy or carbonyl group were found to be particularly efficient. More generally, this work offers new tools for creating molecular complexity and diversity from one of the simplest organic building blocks, formaldehyde.