Imine-Oxazoline (ImOx): A C1-Symmetric N,N-Bidentate Ligand for Asymmetric Catalysis

Asymmetric catalysis relies on the design of chiral ligands, but the variety of nitrogen-based ligands remains limited To address this gap, we have developed a class of C1-symmetric N,N-bidentate ligand, imine-oxazoline (ImOx), derived from amino acids through a four-step synthesis. ImOx features an imine moiety conjugated with a chiral oxazoline ring, as a hybrid of α-diimine (ADI) and pyridine oxazoline (PyOx) ligands. Its low symmetry allows for independent optimization at both coordination sites. ImOx improves the enantioselectivity of palladium-catalyzed conjugate addition reactions, demonstrating a strong correlation between ee and the steric effects on both the imine and oxazoline sites. Studies on well-defined organopalladium intermediates reveal that the steric bulk of ImOx necessitates a cationic pathway to promote alkene insertion. Structural characterization if ImOx suggests a stronger trans-influence compared to PyOx. Moreover, ImOx demonstrates excellent redox activity, promoting the reduction of nickel complexes and stabilizing nickel radical complexes. We anticipate that ImOx will expand the toolkit of chiral N-ligands for asymmetric catalysis.