Synthesis of Benzannulated [5,6] Oxa-Fused/Spiro-Lactones via [4 + 2] Cycloaddition with Quinone Methides: New Insights into Deconjugated Butenolide Reactivity

In this study, we unfold a Lewis-acid-catalyzed inverse electron demand hetero Diels-Alder (IEDHDA) [4 + 2] reaction, leveraging the unique β-selective nucleophilicity of deconjugate lactone in conjunction with quinone methides for the synthesis of polycyclic fused and spiro acetals in a one-pot process. This cascade annulation reaction efficiently generates 3/4 chiral centers with high diastereoselectivity. The developed methodology proceeds under mild reaction conditions and exhibits a broad substrate scope for fused and spiro acetal formation.