Gold and Palladium Relay Catalytic [4+4] Cycloadditions of Enynamides and & gamma;-Methylene-& delta;-valerolactones: Diastereoselective Construction of Furan-Fused Azacyclooctanes

We report a highly efficient and diastereoselective goldand palladiumsequential relay catalysis system for the synthesis of furan-fusedeight-membered heterocycles. Employing a one-pot procedure, easilyaccessible enynamides undergo cyclization to generate azadienes insitu, which subsequently participate in diastereoselective formal[4 + 4] cycloadditions with & gamma;-methylene-& delta;-valerolactones.This strategy enables the rapid and efficient construction of a seriesof furan-fused azacyclooctanes with diverse substituents in good yields(63-97%) and a high level of diastereoselectivity (7:1 & RARR;20:1 dr).

Automated summary

We present a highly efficient and diastereoselective gold and palladium sequential relay catalysis system for the synthesis of furan-fused eight-membered heterocycles. By utilizing a one-pot procedure, readily available enynamides undergo cyclization to generate azadienes in situ, which then engage in diastereoselective formal[4 + 4] cycloadditions with gamma-methylene-delta-valerolactones. This method enables the rapid and efficient construction of a range of furan-fused azacyclooctanes with diverse substituents in good yields (63-97%) and a high level of diastereoselectivity (7:1 → 20:1 dr).