Novel multi-component synthesis of 4-ethynyl substituted pyrrolo[1,2-a]quinoxalines through palladium-catalyzed coupling-coupling reactions

Quinoxaline and its derivatives are an important class of benzoheterocycles displaying a broad spectrum of biological activities which have made them privileged structures in pharmacologically active compounds [1]. Pyrrolo[1,2-a]quinoxalines and their analogues have outstanding roles in natural products [2], displaying broad pharmacological activities such as anti-tumor, adenosine A3 receptor modulator, antiparasitic, and anti-HIV. Moreover, they are significant intermediates for the construction of 5-HT3 receptor agonists. Consequently, the progression of novel and highly efficient methods for the synthesis of pyrrolo[1,2-a]quinoxaline derivatives is highly favorable for drug discovery [3]. In this work, 4-ethynyl-1,3-disubstituted pyrrolo[1,2-a]quinoxalines were synthesized by a multi-component reaction of 1,2-dichloroquinoxaline, terminal alkynes, propargyl alcohol and secondary amines in the presence of a palladium-copper catalytic system. This one-pot process provides a novel synthetic approach for the preparationof 1,3,4-trisubstituted pyrrolo[1,2-a]quinoxalines by the formation of two C-C bonds through palladium-catalyzed two coupling reactions in a single reaction procedure. Allthe new synthesized compounds were characterized by the analytical spectral data.