Switchable Four- and Five-Component Reactions with Perfect Regioselectivity Promoted by Photoredox/Sulfide...

Multicomponent reactions, which involve the reaction of three or more components in a single step to efficiently produce a new molecular structure, have received growing attention in a range of research areas. In this study, four- and five-component reactions incorporating alkenes, carboxylic acids, alkyl radicals, and nitriles are developed for the imidoalkylation of alkenes with perfect regioselectivity. More specifically, this approach involves a photoredox reaction based on a catalytic indirect reductive quenching system. Various drug molecules and amino acids were demonstrated to be compatible substrates for this reaction, thereby enabling the synthesis of multifunctionalized derivatives. Notably, five individual components were assembled with perfect regioselectivity via the reaction of a radical species in the presence of a polarity-matched alkene. Mechanistic studies and density functional theory calculations suggested that this multicomponent reaction involves a cascade of Ritter-type substitutions and Mumm rearrangements. This method exhibits immense potential for use in the creation of structurally diverse and biologically relevant molecules with defined connectivities, thereby holding promise for applications in drug discovery and materials science.