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, enantioselective 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.