Mechanistic advances in multicomponent reactions: a focus on solvent and component effects

Multicomponent reactions (MCRs) are powerful tools in organic synthesis, enabling the rapid assembly of structurally complex molecules from simple building blocks. Despite their synthetic efficiency and broad applicability, the mechanistic pathways underlying these transformations often remain insufficiently understood due to the complex interplay between solvents, reagents, additives, catalysts, and multiple reactive intermediates, which can enable competing reaction pathways. In recent years, advances in computational chemistry and high-resolution mass spectrometry have provided valuable insights into these processes, revealing non -classical features such as the catalytic role of reagents, solvent participation as pseudo -reactants, and the viability of intermediates previously considered unstable. This manuscript highlights representative studies on classical MCRs, including the Biginelli, Passerini, Ugi, and Groebke–Blackburn–Bienaymé reactions, as well as ketene-based variants, emphasizing how mechanistic investigations have reshaped current understanding of these transformations. Particular attention is given to the role of solvents and individual reaction components in modulating reaction pathways and influencing mechanistic outcomes. These studies contribute to a more detailed understanding of multicomponent processes, providing a basis for the rational development and modification of these transformations.