Enantioselective Construction of Eight-Membered N-Heterocycles from Simple 1,3-Dienes via Pd(0) Lewis Base Catalysis.

We report herein an unprecedented enantioselective (4+4) cycloaddition of simple 1,3-dienes with azadienes for the construction of fused eight-membered N-heterocycles. In this transformation, the π-Lewis basic Pd(0) catalyst achieves activation of 1,3-dienes to induce nucleophilic addition to azadienes followed by ring cyclization via a selective terminal allylic substitution. Furthermore, highly efficient and diastereoselective derivatizations of the eight-membered rings provide a facile access to diverse enantiopure fused tetra- to hexacyclic compounds with potential application in medicinal chemistry.