Gold and Palladium Relay Catalytic [4 + 4] Cycloadditions of Enynamides and γ‑Methylene-δ-valerolactones: Diastereoselective Construction of Furan-Fused Azacyclooctanes

We report a highly efficient and diastereoselective gold and palladium sequential relay catalysis system for the synthesis of furan-fused eight-membered heterocycles. Employing a one-pot procedure, easily accessible enynamides undergo cyclization to generate azadienes in situ, which subsequently participate in diastereoselective formal [4 + 4] cycloadditions with γ-methylene-δ-valerolactones. This strategy enables the rapid and efficient construction of a series of furan-fused azacyclooctanes with diverse substituents in good yields (63–97%) and a high level of diastereoselectivity (7:1 → 20:1 dr).