Ni/Cu Cocatalyzed Asymmetric Hydrogenation of Amino Ketones with Water as a Hydrogen Source
Qiongtong Yang, Yao Deng, Hekun Yang, Hongyan Zhao, Pengjie Yao, Jingchao Chen, Zhifeng Ma, Baomin Fan
Abstract
While the asymmetric hydrogenation of protected amino ketones provides straightforward access to chiral amino alcohols, a significant gap exists in developing asymmetric transfer hydrogenation with cost-effective, nonprecious metal catalysts that ensure safety and sustainability. Herein, we present a Ni/Cu cocatalyzed asymmetric reduction of amino ketones employing water as the hydrogen source. This cocatalytic system efficiently converts a broad range of α- and β-amino ketones into their corresponding chiral amino alcohols with high yields and enantioselectivities. The method’s scalability was demonstrated by a successful gram-scale reaction alongside versatile derivatizations leading to eight pharmaceuticals, underscoring the method’s synthetic utility. This approach offers a safe, cost-effective, and easy-handling route to enantioenriched chiral amino alcohols, providing a valuable platform for synthesizing chiral pharmaceuticals and ligands. Additionally, mechanistic insights provided by an in-depth DFT study revealed that the high enantioselectivity and catalytic activity are primarily driven by steric effects within the Ni/Cu catalytic system.