Acetic anhydride to the rescue: Facile access to privileged 1,2,3,4-tetrahydropyrazino[1,2-a]indole core via the Castagnoli-Cushman reaction.

Graphical abstract Highlights • 1,2,3,4-Tetrahydropyrazino[1,2- a ]indole core is featured in many bioactive compounds. • A novel approach to this privileged core is described. • An unsuccessful Castagnoli-Cushman reaction toward this core was rendered workable. • It involves the use of indole-based dicarboxylic acid and acetic anhydride. • It dehydrates the diacid into its cyclic anhydride which enters the reaction. Abstract Indole-fused cyclic anhydrides earlier deemed unreactive in the Castagnoli-Cushman reaction with imines have been rendered valid participant in this process. The new reaction format involves the use of respective indole-based dicarboxylic acids and in situ cyclodehydration of the latter by acetic anhydride. This finding validates a fundamentally new approach to synthesizing compounds based on the privileged 1,2,3,4-tetrahydropyrazino[1,2- a ]indole core characterized by hitherto undescribed substitution pattern. [ABSTRACT FROM AUTHOR]