Regioselective Synthesis of Functionalized Pyrrolo[1,2-a]pyrazine-3,6(2H,4H)-diones via Tandem Post-Ugi Cyclization and Gold(I)-Catalyzed Annulation

Abstract

A convenient synthesis of less explored pyrrolo[1,2-a]pyrazine-3,6(2H,4H)-diones is described in two steps from Ugi adducts. The method involves acid-mediated cyclization of Ugi adducts to form dihydropyrazinones followed by gold(I)-catalyzed regioselective annulation. The generality of the transformation was established by reacting a variety of substituted dihydropyrazinones under the optimized reaction conditions to form densely functionalized pyrrolo[1,2-a]pyrazine-3,6(2H,4H)-diones in good-to-excellent yields. It was also observed some of the acetone-derived Ugi adducts furnish 7-acyl-pyrroloimidazolones as a byproduct during TFA-mediated cyclization via alkyne-carbonyl metathesis and condensation.