Strain-release driven spirocyclization of bicyclo[1.1.0]butanes: access to 6,7-diazaspiro[3.4]octanes

Abstract

The use of ring strain in bicyclo[1.1.0]butanes (BCBs) to facilitate organic transformations is a powerful strategy in organic synthesis. However, their application to the synthesis of spirocyclic scaffolds has remained challenging. Spirocyclobutanes have attracted considerable interest in medicinal chemistry due to their diverse biological activities and potential clinical applications. In this work, we present a method for scandium-catalyzed spirocyclization of simple BCBs with azomethine imines, creating a new platform for the synthesis of previously inaccessible 6,7-diazaspiro[3.4]octanes. We demonstrate the utility of this approach by performing scaled-up reactions and transforming the products, highlighting its synthetic potential.