Copper-Catalyzed\nNucleophilic Cycloisomerization Cascade\nConstructing Azepinoindolizine

Numerous effective bioisosteric replacements have been\nidentified\nthrough substituting scaffolds and functional groups in lead molecules\nwith alternative ones that preserve or enhance the desired biological\nactivity of the original compound. Here, a copper-catalyzed nucleophilic\ncycloisomerization was developed to access potential bioisosteric\nreplacements of azepinoindole. In this process, “tetra-alkene”\ncharacteristic of indolizine undergoes a 12π electrocyclization,\noffering a complementary method to obtain azepinoindolizine derivatives\nthat are otherwise challenging to prepare through conventional means.