Synthesis of 4-Indolylquinoline Bis-Heterocycles from the Reactions of Enone-Tethered Imines with Indoles: Michael/Mannich/Aromatization Sequence

A transition metal-free method to readily assemble 4-indolylquinoline bis-heterocycles has been established using 2-methyleneaminochalcones and indoles in the presence of BF3·OEt2 and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The Lewis acid-promoted Michael addition of indoles to enone-tethered imines followed by an intramolecular Mannich-type reaction provides tetrahydroquinolines. The in situ formed intermediates undergo aromatization that leads to the formation of bis-heterocycles. A variety of bis-heteroarenes has been prepared using this method and tested with a scale-up reaction to showcase the compatibility of this methodology.