Ortho N–H-Directed Divergent Post-Ugi Cascade Cyclization: Additive-Controlled Selective Access to Fused Indazoles and 2,5-Dihydrofurans

Abstract A facile one-pot sequential Ugi/tunable cascade cyclization of indazole-3-carboxylic acid, amines, enynals, and isocyanides has been developed for the divergent construction of two distinct pharmaceutically relevant heterocyclic frameworks: fused polycyclic indazoles and 2,5-dihydrofurans. The ortho N–H moiety of indazole serves as an indispensable neighboring group switch, regulating two independent cyclization pathways. Under metal-free DBU-mediated conditions, intramolecular Michael addition followed by 5-exo-dig cyclization occurs, leading to the formation of dual C–N bonds and the generation of fused indazole polycycles. In contrast, cooperative AgNO3/K2CO3 catalysis triggers a silver-activated alkyne cyclization/ring-opening cascade, selectively forming C–O bonds to afford 2,5-dihydrofuran derivatives. This transformation is characterized by simple additive-switchable selectivity, broad functional group compatibility, gram-scale synthetic practicability, and the simultaneous access to two classes of pharmaceutically relevant heterocycles from identical four-component starting materials.