Nitrogen-containing heterocycles are pervasive structural motifs in bioactive molecules and functional materials, motivating continued efforts toward the development of selective and efficient synthetic strategies. Pyrrolo[2,1-a]isoquinoline derivatives, in particular, have emerged as privileged frameworks of significant current interest. Aminonitriles constitute a unique class of multifunctional synthons, in which the intimate interplay between the amino and cyano groups enables unconventional reactivity patterns, allowing them to function as nucleophiles, iminium precursors, and acyl anion equivalents. Herein, we disclose a mechanistically distinct tandem cyclization strategy that exploits aminomalononitrile as a key reactive intermediate, enabling selective and efficient assembly of pyrrolo[2,1-a]isoquinoline architectures. A highly effective cyclization strategy has been developed under the cooperative action of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and Zn(OTf)₂, wherein tetrahydroisoquinoline-derived aminomalononitriles undergo in situ generation of 1,3-dipoles that subsequently couple with pyridinium 1,4-zwitterionic thiolates to furnish a wide range of pyrrolo[2,1-a]isoquinoline derivatives with moderate to good yields. This protocol is operated under mild conditions and accommodates a broad scope of substrates, providing a concise and versatile approach to cyano-functionalized pyrrolo[2,1-a]isoquinoline scaffolds. Experiment studies suggest that the synergistic interplay between the oxidant and the Lewis acid catalyst plays a pivotal role in enabling this transformation. The experimental procedure is as follows. Under an argon atmosphere, aminomalononitriles 1 (0.3 mmol) was dissolved in dry acetonitrile (2 mL), followed by the addition of DDQ (0.36 mmol). The mixture was stirred at room temperature for 1 h. Upon completion of this step, pyridinium 1,4-zwitterionic thiolate 2 (0.2 mmol) and Zn(OTf)₂ (0.2 equiv.) were added directly to the reaction mixture. The reaction was then heated in an oil bath at 60 ℃ for 36 h. After cooling to room temperature, the mixture was filtered through a Celite pad and washed with dichloromethane (5 mL). The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate, V∶V=10∶1) to afford the desired cyclization product 3.

Key words: cyclization reaction, N-fused heterocyclic framework, aminomalononitrile, 1,3-dipole, pyridinium 1,4-zwitteri- onic thiolate