Utilisation of 1,3‐Dicarbonyl Derivatives in Multicomponent Reactions

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.

/pdf/recent-developments-in-solvent-free-multicomponent-reactions-4ugdax2te0.pdf

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.

A novel microwave-mediated one-pot synthesis of indolizines via a three-component reaction.

Sodium bromide catalysed one-pot synthesis of tetrahydrobenzo[b]pyrans via a three-component cyclocondensation under microwave irradiation and solvent free conditions

One-step synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')- 2H,4H-dihydropyrazolo[3,4-b]pyrans.

Cross-condensation of derivatives of cyanoacetic acid and carbonyl compounds. Part 1: Single-stage synthesis of 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazole-5-carbonitriles

To develop a method of synthesis of the potentially physiologically active compounds, 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazoles, we studied the three-component condensation of substituted piperidin-4-ones, malononitrile and pyrazolin-5-ones. It was found that the electrochemical method of synthesis is more regioselective, the products of the reaction are analytically pure and do not require further recrystallization.

Cross‐Condensation of Derivatives of Cyanoacetic Acid and Carbonyl Compounds. Part 1. Single‐Stage Synthesis of 1′‐Substituted 6‐Amino‐spiro‐4‐(piperidine‐4′)‐2H,4H‐pyrano [2,3‐c]pyrazole‐5‐carbonitriles.

Three-component condensation of 4-piperidinones (7), 5-pyrazolones (8), and malononitrile (4) proceeds chemically and electrochemically and is a convenient one-step means of synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')-2H,4H-dihydropyrazolo[3,4-b]pyrans (12). The electrochemical reactions proceed under milder conditions and with yields 12-15% greater than those of the reactions catalyzed by chemical bases.

Yuliya M. Emeliyanova

Papers

One-step synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')- 2H,4H-dihydropyrazolo[3,4-b]pyrans.

Cross-condensation of derivatives of cyanoacetic acid and carbonyl compounds. Part 1: Single-stage synthesis of 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazole-5-carbonitriles

Cross‐Condensation of Derivatives of Cyanoacetic Acid and Carbonyl Compounds. Part 1. Single‐Stage Synthesis of 1′‐Substituted 6‐Amino‐spiro‐4‐(piperidine‐4′)‐2H,4H‐pyrano [2,3‐c]pyrazole‐5‐carbonitriles.

One-Step Synthesis of Substituted 6-Amino-5-cyanospiro-4-(piperidine-4′)-2H,4H-dihydropyrazolo [3,4-b]pyrans.