Synthesis of Oxindole Spiropyrrolidines Based on [1 + 1 + 1 + 2] Spiroannulation Featuring Release and Reuse of Me₂NH

Presented herein is a synthesis of oxindole spiropyrrolidines via the cascade reaction of <i>N</i>,<i>N</i>-dimethyl enaminone (<b>1</b>) with diazo oxindole (<b>2</b>). The formation of the product involves a Ru-carbene formation-initiated intriguing [1 + 1 + 1 + 2] spiroannulation featuring the release and reuse of dimethylamine. In constructing the pyrrolidine scaffold, <b>1</b> acts as a C1 synthon, <b>2</b> acts as two C1 synthons, and the <i>in situ</i>-released dimethylamine acts as a C1N1 synthon. To our knowledge, this is the first synthesis of oxindole spiropyrrolidine via the simultaneous construction of the pyrrolidine skeleton and the introduction of two oxindole scaffolds via sequential carbene insertion and concurrent C-N/C-H bond activation. In addition, the usefulness of this method is showcased by its suitability for large-scale synthetic scenarios, diverse structural derivation, and potent anticancer activity of the products thus obtained.