Metal-Free Synthesis of Pyrimidine and Naphthoquinone-Fused Pyrroles from Arylglyoxal-Based Domino Reactions

Herein we report acid mediated two and three-component domino reactions of cyclic enamines such as 2-amino-1,4-naphthoquinone, and 6-amino-1,3-dimethyluracil with arylglyoxals for the synthesis of diverse fused pyrroles. The two-component reaction of arylglyoxal and 2-amino-1,4-naphthoquinone in the acetic acid medium provided substituted naphthoquinone-fused pyrroles tethered with hydroxyl and aryl substituents. On the other hand, under similar reaction conditions, the reaction of phenylglyoxal with 6-amino-1,3-dimethyluracil provided an unusual bipyrrolopyrimidine with a quaternary carbon center following a domino reaction involving the formation of five new sigma bonds in one-pot. Interestingly, the reaction of arylglyoxals with 6-amino-1,3-dimethyluracil in ethanol medium in the presence of 10-mol% PTSA provided a three-component product having pyrimidine fused pyrrole linked with 6-aminouracil moiety. We have also developed a three-component reaction of 2-amino-1,4-naphthoquinone, arylglyoxals, and 4-hydroxy-1-methylquinolin-2(1H)-one for the synthesis of naphthoquinone-fused pyrroles linked with hydroxyquinoline derivatives.