Acid-Mediated [3 + 3] or [3 + 2 + 1] Cyclization between Enaminones and 6-Aminouracils to Access 2-Substituted Pyridine Derivatives or 3-Acyl-Substituted Pyrido[2,3-d]pyrimidine-2,4-diones

Abstract

The acid-mediated cyclization reactions of enaminones with6-aminouracils are developed. At room temperature, 2-substituted pyridinederivatives are obtained in 59–75% yields via [3 + 3] cyclization mediated bythe mixed acids FeCl3 and H2C2O4 in equimolar amounts. In addition, thereaction takes place by using FeCl3 and TBHP via a [3 + 2 + 1] cyclization tosynthesize 3-acyl-substituted pyrido[2,3-d]pyrimidine-2,4-diones. Thisprotocol showcases the unique dual reactivity of enaminones, which act notonly as reaction partners but also as one-carbon (C1) building blocks via C–C bond cleavage and C═C bond cleavage. Thismethod features easily accessible starting materials, mild divergent reaction conditions, and high synthetic efficiency. Based oncontrol experiments and previous reports, we have also proposed a plausible mechanism for this reaction.