Aryne Relay-Triggered Three-Component Cascade via In Situ o -QDM Generation: Synthesis of N,O -Spiroheterocycles and Benzo f isoindole-1,3(2 H )-diones

The synthesis of spiroheterocycles via the controllable in situ generation of o-quinodimethanes (o-QDMs) bearing a tetrasubstituted exocyclic C═C bond remains a long-standing synthetic challenge. Herein, we report an aryne relay-triggered three-component (four-molecule) cascade reaction that enables the transition-metal-free assembly of N,O-spiroheterocycles (32 examples, up to 94% yield, mostly d.r. > 20:1) and benzofisoindole-1,3(2H)-diones (27 examples, up to 84% yield). This transformation uses readily available 2-benzyl oxazolines, aryne precursors, and electron-deficient alkenes as starting materials, proceeding through the in situ generation and selective trapping of the aforementioned o-QDM intermediates. The protocol exhibits a broad substrate scope, and its synthetic utility is further validated by gram-scale synthesis and versatile product derivatization.