Stereoselective synthesis of 3,3′-spirooxindoles with higher order heterocycles

Despite the current advancement accomplished in the asymmetric construction of spirocyclic oxindoles fused with three- to six-membered heterocycles, accessing enantioenriched spirooxindoles fused with larger heterocycles has been far less successful. Inspired by the substantial medicinal and biological activities of spirooxindoles, characterized by their unique structural features, the construction of these compounds, especially those incorporating larger heterocycles, is extremely desired. However, this endeavor remains a challenging task due to the complexity of their structures and the need for precise stereoselectivity in synthesis. In this review article, we aim to provide a concise overview of the stereoselective strategies developed for the construction of spirooxindoles featuring larger heterocycles over the past few years. While summarizing the progress achieved so far, we have also explored the reaction mechanisms and examined the challenges encountered during reaction discovery, in order to advance this field further.