Multicomponent reactions have gained significant importance as a tool for the synthesis of a wide variety of useful compounds, including pharmaceuticals. In this context, the multiple component approach is especially appealing in view of the fact that products are formed in a single step, and the diversity can be readily achieved simply by varying the reacting components. The eco-friendly, solvent-free multicomponent approach opens up numerous possibilities for conducting rapid organic synthesis and functional group transformations more efficiently. Additionally, there are distinct advantages of these solvent-free protocols since they provide reduction or elimination of solvents thereby preventing pollution in organic synthesis “at source”. The chemo-, regio- or stereoselective synthesis of high-value chemical entities and parallel synthesis to generate a library of small molecules will add to the growth of multicomponent solvent-free reactions in the near future. In this review we summarized the results reported mainly within the last 10 years. It is quite clear from the growing number of emerging publications in this field that the possibility to utilize multicomponent technology allows reaction conditions to be accessed that are very valuable for organic synthesis. Therefore, diversity oriented synthesis (DOS) is rapidly becoming one of the paradigms in the process of modern drug discovery. This has spurred research in those fields of chemical investigation that lead to the rapid assembly of not only molecular diversity, but also molecular complexity. As a consequence multi-component as well as domino or related reactions are witnessing a new spring.

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Recent developments in solvent-free multicomponent reactions: a perfect synergy for eco-compatible organic synthesis

An efficient one-pot synthesis of spirooxindole derivatives by three-component reaction of isatins, malononitrile (cyanoacetic ester) and 1,3-dicarbonyl compounds in water in the presence of l-proline is reported This new protocol has the advantages of environmental friendliness, higher yields, shorter reaction times, low cost, and convenient operation

Efficient one-pot synthesis of spirooxindole derivatives catalyzed by L-proline in aqueous medium.

Solvent-free multicomponent synthesis of pyranopyrazoles: per-6-amino-β-cyclodextrin as a remarkable catalyst and host

Eco-friendly synthesis and biological evaluation of substituted pyrano[2,3-c]pyrazoles

A novel and efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-b]quinoline]dione, spiro[furo[3,4-e]pyrazolo[3,4-b]pyridine-4,3′-indoline]dione, and spiro[indeno[2,1-e]pyrazolo[3,4-b]pyridine-4,3′-indoline]dione derivatives via three-component reaction of isatin, 5-amino-3-methylpyrazole, and 1,3-dicarbonyl compounds in aqueous medium is described. The advantages of this method include high efficiency, mild reaction conditions, convenient operation, and environmentally benign conditions.

Efficient One-Pot Synthesis of Novel Spirooxindole Derivatives via Three-Component Reaction in Aqueous Medium

Three‐Component One‐Pot Synthesis of 1,4‐Dihydropyrano[2,3‐c]pyrazole Derivatives in Aqueous Media

An efficient synthesis of pyrimido[4,5‐b]quinoline derivatives via three‐component reaction in aqueous media

The reaction of substituted cinnamonitriles and 4-amino-2,6-dihydroxypyrimidineor2,4-diamino-6-hydroxypyrimidine in water in the presence of triethylbenzylammonium chloride (TEBA) as catalyst affords a clean synthesis of pyrido[2,3-d]pyrimidine derivatives.

Clean synthesis of pyrido[2,3-d]pyrimidines in aqueous media

The reaction of 4-hydroxy-6-methylpyran-2-one with substituted cinnamonitriles in water in the presence of triethylbenzylammonium chloride (TEBA) provide an efficient route to 2-amino-4-aryl-4H,5H-pyrano[3,2-c]pyran-5-onederivatives. The products were characterised by IR, 1 H NMR, elemental analysis and were further confirmed by the X-ray crystal structure analysis.

Lihui Niu

Papers

Three‐Component One‐Pot Synthesis of 1,4‐Dihydropyrano[2,3‐c]pyrazole Derivatives in Aqueous Media

An efficient synthesis of pyrimido[4,5‐b]quinoline derivatives via three‐component reaction in aqueous media

Clean synthesis of pyrido[2,3-d]pyrimidines in aqueous media

Synthesis of 4H,5H-pyrano[3,2-c]pyrano-5-ones in aqueous media

One-Pot Synthesis of Pyrido[2,3-d]pyrimidines via Efficient Three-Component Reaction in Aqueous Media.