A Facile Synthesis of 4,6,7,8,8a,9-Hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines by a Three-Component Coupling Reaction Followed by Intramolecular 1,3-Dipolar Cycloaddition

A practical and efficient two-step protocol for the synthesis of several new 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines is described. The first step involves the AuBr3-catalyzed three-component coupling reaction of terminal alkynes, aldehydes, and amines under solvent-free conditions to provide the requisite propargylamines. The reaction tolerates a high structural diversity, requires only short reaction times, gives high diastereoselectivities, and is environmentally benign. Furthermore, the propargylamine products undergo catalyst-free intramolecular azide-alkyne [3 + 2] dipolar cycloaddition reactions to give the 4,6,7,8,8a,9-hexahydropyrrolo[1,2-a][1,2,3]triazolo[1,5-d]pyrazines in excellent yields and with excellent diastereoselectivities.