Design and Synthesis of Chiral Bidentate Phosphine-Free 2‑Hydroxypyridine-Oxazoline Ligands for Manganese-Catalyzed Hydrogenation

Significant progress has been made in the development of tridentate phosphine ligands for manganese-catalyzed asymmetric direct hydrogenation (ADH). However, their high cost and susceptibility to oxidation limit their further application. In contrast, bidentate phosphine-free ligands, such as bidentate nitrogen-based ligands, remain underexplored in the context of manganese-catalyzed asymmetric hydrogenation. Herein, we have developed a series of chiral 2-hydroxypyridine-oxazoline ligands with tunable steric and electronic properties. These ligands are characterized by exhibiting tautomerism between 2-hydroxypyridine and pyridone, which enhances hydrogen activation, hydride transfer, and nucleophilicity of the hydride species. They were applied in manganese-catalyzed asymmetric hydrogenation of heteroaromatics, simple ketones, and ketimines with high yields and enantioselectivities. Preliminary mechanistic studies and DFT calculations revealed the critical role of the ligand in facilitating manganese-catalyzed asymmetric hydrogenation, shedding light on the possible catalytic pathways. These findings demonstrate the promising potential of chiral 2-hydroxypyridine-oxazoline ligands as an efficient N,N-ligand scaffold for asymmetric catalysis.