Yanlong Gu

Multicomponent reactions in unconventional solvents: state of the art

Simple and green synthetic procedures constitute an important goal in organic synthesis. The combination of multicomponent reactions (MCRs) and unconventional solvents has become a new research direction, which enables simultaneous growth of both MCRs and green solvents toward ideal organic synthesis. This review summarizes recent results of MCRs obtained in unconventional media including water, ionic liquids, polyethylene glycol and bio-based solvents.

Glycerol as a sustainable solvent for green chemistry

Glycerol, an organic waste generated by the biodiesel industry, has been recently proposed as a valuable green solvent. This review summarizes the advantages, disadvantages and potential uses of glycerol as a green solvent for catalysis, organic synthesis, separations and materials chemistry. In particular, through selected examples we show here that glycerol may combine the advantages of water (low toxicity, low price, large availability, renewability) and ionic liquids (high boiling point, low vapour pressure, low solubility in scCO2). More generally, all these reported works contribute to increase the portfolio of available green solvents and afford innovative solutions to the substitution of the conventionally used volatile organic solvents.

Bio-based solvents: an emerging generation of fluids for the design of eco-efficient processes in catalysis and organic chemistry.

Biomass and waste exhibit great potential for replacing fossil resources in the production of chemicals. The search for alternative reaction media to replace petroleum-based solvents commonly used in chemical processes is an important objective of significant environmental consequence. Recently, bio-based derivatives have been either used entirely as green solvents or utilized as pivotal ingredients for the production of innovative solvents potentially less toxic and more bio-compatible. This review presents the background and classification of these new media and highlights recent advances in their use in various areas including organic synthesis, catalysis, biotransformation and separation. The greenness, advantages and limitations of these solvents are also discussed.

Glycerol as a promoting medium for electrophilic activation of aldehydes: catalyst-free synthesis of di(indolyl)methanes, xanthene-1,8(2H)-diones and 1-oxo-hexahydroxanthenes

Glycerol was used, for the first time, as a green and effective promoting medium for electrophilic activation of aldehydes, and with which, a catalyst-free system for some reactions that conventionally carried out using acid catalysts, such as synthesis of di(indolyl)methanes, 3,4,5,6,7,9-hexahydro-9-aryl-1H-xanthene-1,8(2H)-dione and 1-oxo-hexahydroxanthenes, was developed.

Brønsted acid ionic liquid-catalyzed reductive Friedel–Crafts alkylation of indoles and cyclic ketones without using an external reductant

In the absence of an external reductant, C3-cycloalkylated indole could be synthesized through reductive alkylation of indole with cyclic ketone using a sulfonyl-functionalized Bronsted acid ionic liquid as a catalyst. Water generated in the initial stage of the reaction played a key role in rendering the reductive coupling possible. The reaction proceeds most likely in a radical way.

Facile construction of densely functionalized 4H-chromenes via three-component reactions catalyzed by L-proline

Three-component reactions of salicylaldehydes, 1,3-cyclohexanediones and a sulfur, carbon, or nitrogen-based nucleophile were developed, for the first time, by using L-proline as a catalyst, which generated various substituted 4H-chromene derivatives in good to excellent yields. The reactions were performed in ethanol under mild and metal-free conditions. In these reactions, the use of L-proline as a catalyst was proven to be key for rendering the reactions possible because replacing L-proline with other acids or bases resulted in the generation of many side products. Many nucleophiles, such as thiophenols, mercaptans, indoles, sulfinic acid, benzotriazole, 2-naphthol, 5-methyl-2-phenyl-1,2-dihydropyrazol-3-one, 6-aminouracil, 6-amino-1,3-dimethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione and some commonly used C–H acids including 4-hydroxycoumarin, 2-hydroxy-1,4-naphthoquinone and barbituric acid could be successively used to assemble with dimedone and salicylaldehyde. Particularly, the product generated from the reaction of benzotriazole, 3-methoxysalicylaldehyde and dimedone can also be used as a starting material, in which the fragment of benzotriazole acts as a leaving group, for the synthesis of some important compounds by reacting with many carbon-based nucleophiles, such as dibenzoylmethane, ethyl benzoylacetate, 1,3-cyclohexanedione, N,N-dimethylaniline, 2-methylfuran and sesamol in acidic conditions. This offers a complementary route to access some 4H-chromenes that cannot be attained with the above-mentioned three-component reactions.

Catalyst-free aqueous multicomponent domino reactions from formaldehyde and 1,3-dicarbonyl derivatives

Here we report a catalyst-free aqueous multicomponent domino reaction (MCR) capable of affording a wide range of valuable dihydropyran derivatives from simple, cheap and readily available reactants such as formaldehyde, 1,3-dicarbonyl derivatives, styrene, indole and aniline derivatives. Within the framework of green chemistry, these MCRs gather many advantages such as (i) utilization of water as a solvent, (ii) creation of up to six bonds in one sequence, (iii) 100% of carbon economy and (iv) water as a sole waste. These MCRs exhibit a broad substrate scope and open access to valuable chemicals traditionally produced through multistep processes involving catalysts or organic solvents. More generally, this work opens a new way for creating molecular complexity with maximum simplicity.

PdCl2(py)2 encaged in monodispersed zeolitic hollow spheres: a highly efficient and reusable catalyst for Suzuki–Miyaura cross-coupling reaction in aqueous media

By encaging the PdCl2(py)2 complex (py = pyridine) in the interior space of silicalite-1 hollow spheres (SHS), a novel solid palladium catalyst, PdCl2(py)2@SHS, was successfully prepared. The structure and composition of the solid catalyst was characterized by SEM, TEM, XRD, N2 sorption, FT-IR and XPS. This catalyst afforded fast conversions for the Suzuki–Miyaura cross-coupling reactions of various aryl halides and arylboronic acids even at Pd loadings of 0.0188 mol% in aqueous media. The turnover frequency (TOF) could be up to 63 210 h−1 under mild conditions in air. In particular, because of the antileaching effect of the surrounding zeolitic shell toward the entrapped Pd species, PdCl2(py)2@SHS showed outstanding stability and reusability, which could be reused at least 10 times without appreciable loss of its activity. The developed solid catalyst combined with the mild conditions represented one of the most efficient heterogeneous systems for the Suzuki–Miyaura cross-coupling reactions of aryl halides.

Water mediated trapping of active methylene intermediates generated by IBX-induced oxidation of Baylis–Hillman adducts with nucleophiles

Water proved to be an efficient solvent for oxidation of a Baylis–Hillman adduct with IBX. The generated product, a methylene intermediate, could be trapped in situ by many nucleophiles in water, such as styrenes, β-dicarbonyl compounds, benzamide and less reactive indoles. This strategy offers an alternative way to methylenylation of β-dicarbonyl compounds with formaldehyde for the formation of a methylene intermediate, thus allows the use of some nucleophiles that are chemically unstable to formaldehyde. The use of water as solvent, good recycling ability of IBX oxidant and wide substrate scopes make these reactions very attractive from the viewpoint of green chemistry.

Gluconic acid aqueous solution as a sustainable and recyclable promoting medium for organic reactions

For the first time, gluconic acid aqueous solution (GAAS), a biobased weakly acidic liquid, was used as an effective promoting medium for organic reactions, such as the Michael addition of indoles to α,β-unsaturated ketones, the electrophilic ring-opening reaction of 3,4-dihydropyran with indoles and Friedel–Crafts alkylation of electron-rich aromatics with benzyl alcohols. The concept of using GAAS as a solvent for organic reactions not only offers a sustainable candidate for progress in solvent innovation, but also opens up a new avenue for the utilization of this biobased polyhydroxylated acid. Among the features that render GAAS as a solvent so interesting is the ability to act as both the reaction medium and catalyst. Moreover, this methodology offers significant improvements with regard to the yield of products, simplicity in operation, cost efficiency and green aspects, in terms of avoiding toxic catalysts and minimizing the generation of waste.