Electrochemically Driven Strain-Release Dearomative (3+2) Cyclization for the Synthesis of Bicyclo[2.1.1]hexane-Fused Polycyclic Spiroindolines

Abstract

Spiroindolines are ubiquitous structural motifs in natural products and biologically active compounds, making the development of reliable synthetic methods for their construction highly important to the synthetic chemistry community. Moreover, the synthesis of polycyclic compounds featuring C(sp3)-rich and complex three-dimensional (3D) architectures and multiple contiguous quaternary carbon centers in a single step remains a formidable challenge. Herein, we report an efficient and environmentally friendly electrochemical strategy for a dearomative (3+2) cyclization reaction of C3-bicyclo[1.1.0]butane (BCB)-substituted indoles. This method enables the efficient assembly of structurally complex and novel bicyclo[2.1.1]hexane (BCH)-fused polycyclic spiroindolines in high yields, featuring four contiguous stereogenic centers, two of which are spirocyclic all-carbon quaternary carbon centers. This new methodology provides a series of valuable spiroindolines under mild reaction conditions in a practical and atom-economic manner without the need for external oxidants, and the products can be further transformed into more complex spiroindolines. Notably, these C(sp³)-rich products exhibit significant potential in the field of medicinal chemistry.