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 benzo[ f ]isoindole-1,3(2 H )-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.