Cascade [3 + 2]/[4 + 2] Cycloaddition of Enaminones with Vinylene Carbonate for the Synthesis of Functionalized Pyrrolo[2,1-<i>a</i>]isoquinoline Derivatives
Jianbo Ma, Qing-Sheng Zhao, Yi-Mai Yin, Shu Yang, Jiaqi Shao, Sheng‐Jiao Yan
Abstract
We developed a protocol for the synthesis of functionalized pyrrolo[2,1- a ]isoquinoline derivatives (PIQDs) 3 from enaminones 1 using vinylene carbonate 2 . This strategy involved [3 + 2] and [4 + 2] cycloadditions via heating a mixture of substrates 1 with vinylene carbonate 2 and DCE at 60 °C, catalyzed by [Cp*RhCl 2 ] 2 and oxidized with Cu(OAc) 2 and AgSbF 6 promoted by NaOAc. As we increased the reaction temperature to 110 °C under the same conditions, we synthesized PIQDs 4 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 3 – 4 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 ( 3 – 4 ). 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.