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.

Automated summary

In this study, acid-mediated two and three-component domino reactions of cyclic enamines with arylglyoxals were reported for the synthesis of diverse fused pyrroles. Different reaction conditions led to the formation of various fused pyrrole structures with different substituents. These reactions provide a convenient and efficient strategy for the synthesis of complex pyrrole-containing compounds.