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

We developed a protocol for the synthesis of functionalized pyrrolo[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 [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, catalyzed by [Cp*RhCl₂]₂ and oxidized with Cu(OAc)₂ and AgSbF₆ promoted by NaOAc. As we increased the reaction temperature to 110 °C under the same conditions, we synthesized PIQDs <b>4</b> through sequential C-H activation, alkene insertion, migratory insertion, C-N reductive elimination, β-O elimination, and finally dehydration. As a result, a series of PIQDs <b>3</b>-<b>4</b> were generated by forming four bonds (2 C-C and 2 C-N bonds) in a single step. This strategy realizes the synthesis of linear molecules with potential biological activity, specifically natural-like heterocycles (<b>3</b>-<b>4</b>). It expands the application of vinylene carbonate as a C2 synthon in the construction of pyrrole and isoquinoline skeletons for the synthesis of functionalized PIQDs in combinatorial and parallel syntheses via one-pot reactions.