Asymmetric Allylic Dearomatization of Quinolines via Dynamic Ligand Exchange

ABSTRACT The strong coordination of quinolines to transition metals typically interferes with chiral catalysts, restricting their use in asymmetric synthesis. Here, we harness this challenging property as a stereocontrol element through the integration of dynamic ligand exchange with designed hydrogen‐bonding interactions between a chiral phosphine ligand and the quinoline substrate. This creates a confined microenvironment that stabilizes the chiral palladium complex and directs a highly enantioselective allylic amination/alkynylation cascade. This approach enables the first asymmetric allylic dearomatization of quinolines with terminal alkynes, affording a broad range of N‐heterocycles bearing two stereocenters in good yields (up to 85%) with excellent enantioselectivities (up to 99% e.e.) and diastereoselectivities (>20:1 d.r.). Mechanistic studies, including in situ 31 P NMR and DFT calculations, reveal that the hydrogen‐bond interactions are essential for dynamic ligand exchange, and their disruption leads to loss of enantiocontrol. This work demonstrates that dynamic regulation of the ligand‐exchange equilibrium can be an effective strategy for harnessing strong substrate coordination in asymmetric catalysis.