A Mechanochemical Approach for the Friedel–Crafts Cyclization Reaction of in-situ Formed α-Imino Ketones

Abstract We report an efficient [5+1] annulation of 1-(2-aminophenyl)pyrroles with α-keto aldehydes for the synthesis of pyrrolo[1,2-a]quinoxaline derivatives utilizing a mechanochemical approach. This cascade transformation proceeds through the in-situ formation of an α-imino ketone intermediate, followed by an intramolecular Friedel–Crafts cyclization and subsequent aerial oxidation to establish the quinoxaline core. The versatility of this methodology is further demonstrated by its successful extension to the synthesis of indolo-quinoxalines, showcasing broad substrate compatibility. This sustainable, metal-free protocol is highly practical, featuring high functional group tolerance, efficient scalability to the gram scale, and straightforward postsynthetic modification of the resulting scaffolds.