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Aryne Relay-Triggered Three-Component Cascade via In Situ o-QDM Generation: Synthesis of N,O-Spiroheterocycles and
Wenbo Cai1, Boyang Dong1, Beiling Gao1
1College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
Abstract:
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(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.
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