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

A novel and regioselective umpolung synthesis of spirooxindoles has been developed by cooperative NHC–Lewis acid-mediated formal [3 + 2] annulations of alkynyl aldehydes with isatins. In most cases, the reactions proceeded via a3–d3 umpolung of alkynyl aldehydes resulting in spirooxindole butenolides. In a few cases, spirooxindole furan-3(2H)-ones were formed as the major products via an a1–d1 umpolung process by controlling the reaction temperature. These newly formed spirooxindoles could provide promising candidates for chemical biology and drug lead discovery.

Cooperative N-heterocyclic carbene (NHC)–Lewis acid-mediated regioselective umpolung formal [3 + 2] annulations of alkynyl aldehydes with isatins

Synthetic methodology for the synthesis of heterocycles is of continuous and high interest with applications in materials, catalysis, and medicines. Multicomponent reactions are suitable tools to efficiently generate chemically diverse sets of heterocycles with sufficient structural complexity. Especially isocyanides have proven to be particularly versatile building blocks in these one-pot processes. Due to their electronic structure, isocyanides are able to act sequentially or simultaneously as a nucleophile and an electrophile. Traditionally, isocyanides are therefore frequently used in multicomponent chemistry. In the recent literature, numerous reactions have been reported that involve formal cycloadditions of isocyanides with conjugated heterodienes. This Focus Review aims at mapping this reactivity and at providing insight into the relationship between the various reported reaction partners and the observed reactivity modes.

Synthesis of Heterocycles by Formal Cycloadditions of Isocyanides

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/hc.21362

ZnO‐NR as the efficient catalyst for the synthesis of new thiazole and cyclopentadienone phosphonate derivatives in water

Visible-Light-Induced Photocatalytic Synthesis of β-Keto Dithiocarbamates via Difunctionalization of Styrenes.

A novel isocyanide-based three-component reaction: a facile synthesis of substituted 2H-pyran-3,4-dicarboxylates

Efficient synthesis of functionalized butenolides mediated by vinyltriphenylphosphonium salts in aqueous media

An efficient method for synthesis of 2H-pyran-3,4-dicarboxylates using the three-component reaction of dithiocarbamates, dialkyl acetylenedicarboxylates, and isocyanides in solvent-free conditions is described. In these reactions, synthesis of dithiocarbamates is possibly based on the one-pot reaction of secondary amines, CS2, and alkyl halides in solvent-free conditions without using a catalyst. The mild reaction conditions and high yields of the reaction exhibit the good synthetic advantage of these methods.

A Novel Isocyanide‐Based Three‐Component Reaction: A Facile Synthesis of Substituted 2H‐Pyran‐3,4‐dicarboxylates.

The reaction of esters (II) with triphenylphosphine results in formation vinyltriphenylphosphonium salts which react with carbonyl compounds (I) or (IV) to produce highly functionalized butenolides.

Adel Hasannia

Papers

A novel isocyanide-based three-component reaction: a facile synthesis of substituted 2H-pyran-3,4-dicarboxylates

Efficient synthesis of functionalized butenolides mediated by vinyltriphenylphosphonium salts in aqueous media

A Novel Isocyanide‐Based Three‐Component Reaction: A Facile Synthesis of Substituted 2H‐Pyran‐3,4‐dicarboxylates.

Efficient Synthesis of Functionalized Butenolides Mediated by Vinyltriphenylphosphonium Salts in Aqueous Media.