Regioselective Multicomponent Approach Promoted by <i>p‐</i> TSA: A Facile Synthetic Access to 3,5‐disubstituted 4‐pyridinone Frameworks

Abstract A facile multicomponent strategy for the regioselective synthesis of 3,5‐disubstituted 4‐pyridinone frameworks has been developed using Brønsted acid ( p‐TSA ) as promoter. The reaction proceeds via a cascade manner by involving C─O bond cleavage with concomitant C─C and C─N bond formation from readily available 3‐formyl chromones, N, N ‐disubstituted enaminones, and substituted amines yielding 3,5‐disubstituted 4‐pyridinone frameworks. This approach is cost‐effective, atom economy, wide substrate scope, and delivers the considerable yields including a gram‐scale synthesis. The plausible reaction mechanism was also investigated by trapping some of the transient intermediates involved in the process using ESI‐MS. The methodology is amicable in the generation of a library of pyridinone based heterocyclic scaffolds and can be further utilized in the drug discovery process.