Synthesis of 3,4-Dihydropyridin-2-ones via Domino Reaction under Phase Transfer Catalysis Conditions

Abstract

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu4N+HSO4– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials.

Keywords

• tandem reaction
• S-2,2,2-trifluoroethyl 1,3-dithiane-2-carbothioate
• 3,4-dihydropyridin-2-ones
• Michael addition
• acyl anion equivalent
• phase transfer catalysis