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This work demonstrates a novel IED-HDA reaction enabling efficient synthesis of spirocyclic compounds, suggesting its utility in drug development.
The spirocyclic 2,2-dimethylchromane skeleton holds significant potential for applications in drug discovery; however, its synthesis remains underdeveloped and challenging. Herein, we report an FeCl₃-promoted aerobic IED-HDA reaction of in situ-generated oxindole-embedded o-QMs, in which tert-butanol serves as an ideal equivalent of gaseous isobutene. This method enables efficient access to a diverse array of structurally novel 2,2-dimethylchromane spirooxindoles in generally good yields. Notable advantages include operational simplicity, high atom economy, excellent functional group compatibility, and facile derivatization of products, thereby meeting the demands of synthetic approaches for lead discovery.
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Ge et al. (2026) studied this question.
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