Finding Reaction Pathways for Multicomponent Reactions: The Passerini Reaction is a Four-Component Reaction

摘要

Multicomponent reactions (MCRs), in which three or more molecules react in one pot and generate products containing almost all atoms of the reactant molecules, have been developed extensively as tools to achieve highly atom-, step-, and energy-economic organic syntheses.The Passerini reaction, which is formally a three-component reaction involving a carboxylic acid, an aldehyde (or ketone), and an isocyanide to generate an α-acyloxycarboxamide, is the most fundamental MCR involving isocyanides. A conventional mechanism of this reaction is shown in Scheme 1, where the reaction takes place efficiently at or below room temperature, in apolar solvent, and with high concentration of reactants. Here we present a quantum chemical study of all possible pathways among three reactant molecules of the Passerini reaction using a new theoretical approach for finding transition states (TSs) and propose the most probable pathway without prejudice for presumed pathways or mechanisms.