Multicomponent reactions with Meldrum's acid and isocyanides as a valuable synthetic approach: An update

Multicomponent reactions (MCRs) are one-pot processes in which at least three reactants are combined to assemble a novel target product by intrinsic molecular diversity, optimal atom economy, and high efficiency. The development and design of new MCRs that yield valuable chemical products represent a major focus in organic chemistry. Meldrum's acid is a distinctive β-keto ester that is crucial in organic synthesis, especially in MCRs. The C5 position of this molecule demonstrates significant reactivity towards electrophilic substitution, whereas the carbonyl centers at C4 and C6 are notably vulnerable to nucleophilic attack. Its dual characteristics as both a nucleophile and electrophile, along with its tendency for enolization and decarboxylation, render it an essential synthon for the effective assembly of various heterocyclic scaffolds and acyclic organic compounds. In parallel, isocyanides have attracted significant attention as a versatile building block in MCRs because of their unique ambident reactivity. The combination of Meldrum's acid with isocyanide has opened a powerful avenue in diversity-oriented synthesis, leading to the discovery of unexpected products such as succinimide, carboxamide, imino-furopyranones, cyclopenta[b] pyridines, benzodiazepines, benzooxazepines, amidodiesters, functionalized triamides, and enamides. In continuation of our earlier review on Meldrum's acid and isocyanide-based MCRs, this minireview covers an in-depth discussion of this field, especially focusing on the most recent results from 2015 to 2025.