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

An efficient multicomponent cascade synthesis of 3,5-disubstituted 4-pyridinones involving C─O cleavage with concomitant C─C/C─N bond formation is reported.

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.

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