Construction of Fused Polyheterocycles through Sequential [4 + 2] and [3 + 2] Cycloadditions

A method for Pd-catalyzed aerobic oxidative reaction of quinazolinones and alkynes has been developed for sequential [4 + 2] and [3 + 2] cycloadditions to assemble a novel fused-polycyclic system containing tetrahydropyridine and dihydrofuran rings. The reaction process involves C-H and N-H bond functionalization for the formation of tetrahydropyridine and an oxygen radical cyclization for the dihydrofuran ring. This atom- and step-economical synthesis is highly efficient and has good substrate tolerance, which provides a new approach for the construction of polycyclic molecules with potential pharmaceutical interest.