Temperature-Controlled Divergent Asymmetric Synthesis of Indole- Based Medium-Sized Heterocycles through Palladium Catalysis

The divergent construction of chiral medium-sized rings is an essential but challenging task in organic synthesis. Herein, we report a temperature-controlled catalytic system for the divergent, enantioselec-tive synthesis of different types of medium-sized rings starting from the same substrate set. Enabled by a planar chiral bisphosphine ligand, the palladium-catalyzed (5 + 4) and formal (5 + 2) annulations of cyclic aza-dienes and vinylethylene carbonates proceeded smoothly to afford a broad spectrum of indole-based medium-sized heterocycles in excellent yields with outstanding enantioselectivities. Those products could be further diversified through various functional group transformations. Moreover, mechanistic studies, including control experiments and DFT calculations, shed light on understanding the observed regio-and enantioselectivities of palladium-catalyzed (5 + n) cyclization.