Ring-Rearrangement-Driven Formal (3+2) Cycloaddition of Enaminone-Based Thioalkynes with Nitriles to Form Thiazole-Containing Bis-heterocycles

Abstract

Herein, we report a one-pot synthesis of 3,4-dihydropyridin-2(H)-one containing thiazole derivatives by Bronsted acid-mediated ring-rearrangement and formal (3+2) cycloaddition reaction of enaminone-based thioalkyne with alkyl/aryl nitrile. The developed protocol demonstrates a wide substrate scope for both the reacting partners with high atom-economy furnishing very high to excellent yields of pharmaceutically relevant bis-heterocyclic derivatives. Based on outcome of the product and control experiments, a plausible reaction mechanism has also been proposed. The gram-scale synthesis and further synthetic transformation demonstrate the synthetic efficacy and utility of the developed protocol.