Cascade [3 +\n2]/[4 + 2] Cycloaddition of Enaminones\nwith Vinylene Carbonate for the Synthesis of Functionalized Pyrrolo[2,1‑<i>a</i>]isoquinoline Derivatives

We developed a protocol for the synthesis of functionalized\npyrrolo[2,1-<i>a</i>]isoquinoline derivatives (PIQDs) <b>3</b> from enaminones <b>1</b> using vinylene carbonate <b>2</b>. This strategy involved\n[3 + 2] and [4 + 2] cycloadditions via heating a mixture of substrates <b>1</b> with vinylene carbonate <b>2</b> and DCE at 60 °C,\ncatalyzed by [Cp*RhCl<sub>2</sub>]<sub>2</sub> and oxidized with Cu(OAc)<sub>2</sub> and AgSbF<sub>6</sub> promoted by NaOAc. As we increased\nthe reaction temperature to 110 °C under the same conditions,\nwe synthesized PIQDs <b>4</b> through sequential C–H\nactivation, alkene insertion, migratory insertion, C–N reductive\nelimination, β-O elimination, and finally dehydration. As a\nresult, a series of PIQDs <b>3</b>–<b>4</b> were\ngenerated by forming four bonds (2 C–C and 2 C–N bonds)\nin a single step. This strategy realizes the synthesis of linear molecules\nwith potential biological activity, specifically natural-like heterocycles\n(<b>3</b>–<b>4</b>). It expands the application\nof vinylene carbonate as a C2 synthon in the construction of pyrrole\nand isoquinoline skeletons for the synthesis of functionalized PIQDs\nin combinatorial and parallel syntheses via one-pot reactions.