Carboxylate migration from ethyl cyanoformate to methylene: rapid access toward pyrrolo[1,2-a]pyrazines

Abstract

In this paper, a novel method is developed to prepare a series of multi-functionalised pyrrolo[1,2-a]pyrazines using a substituted N-alkylated pyrrole intermediate, ethyl cyanoformate, and ammonium acetate. Ethyl cyanoformate is identified as a distinctive source of the ethyl carboxylate group, enabling for the first time, the formation of a new C–C bond with an active methylene group under basic conditions. This transformation affords a 1,5-dicarbonyl precursor, which subsequently undergoes cyclization with the nitrogen source to yield multi-functionalised pyrrolo[1,2-a]pyrazines. The method demonstrates a broad substrate scope and exhibits excellent tolerance towards diverse functional groups.