Design and Synthesis of Chiral Bidentate Phosphine-Free 2-Hydroxypyridine-Oxazoline Ligands for Manganese-Catalyzed Hydrogenation
Gao‐Wei Wang, Mu‐Wang Chen, Yaqi Wu, Qing‐Xian Xie, Zheng Liu, Rong‐Zhen Liao, Yong‐Gui Zhou
Abstract
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.