Mechanism Studies of Ir-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids

• Published in: Journal of the American Chemical Society Vol. 139; no. 1; pp. 541 - 547
• Main Authors: Li, Mao-Lin, Yang, Shuang, Su, Xun-Cheng, Wu, Hui-Ling, Yang, Liang-Liang, Zhu, Shou-Fei, Zhou, Qi-Lin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11.01.2017
• Subjects: alkenes; carboxylic acids; catalysts; enantiomers; hydrogen; hydrogenation; iridium; ligands; nuclear magnetic resonance spectroscopy; value added
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.6b11655

The Ir-catalyzed asymmetric hydrogenation of olefins is widely used for production of value-added bulk and fine chemicals. The iridium catalysts with chiral spiro phosphine-oxazoline ligands developed in our group show high activity and high enantioselectivity in the hydrogenation of olefins bearing a coordinative carboxyl group, such as α,β-unsaturated carboxylic acids, β,γ-unsaturated carboxylic acids, and γ,δ-unsaturated carboxylic acids. Here we conducted detailed mechanistic studies on these Ir-catalyzed asymmetric hydrogenation reactions by using (E)-2-methyl-3-phenylacrylic acid as a model substrate. We isolated and characterized several key intermediates having Ir–H bonds under the real hydrogenation conditions. Particularly, an Ir­(III) migratory insertion intermediate was first isolated in an asymmetric hydrogenation reaction promoted by chiral Ir catalysts. That this intermediate cannot undergo reductive elimination in the absence of hydrogen strongly supports the involvement of an Ir­(III)/Ir­(V) cycle in the hydrogenation. On the basis of the structure of the Ir­(III) intermediate, variable-temperature NMR spectroscopy, and density functional theory calculations, we elucidated the mechanistic details of the Ir-catalyzed hydrogenation of unsaturated carboxylic acids and explained the enantioselectivity of the reactions. These findings experimentally and computationally elucidate the mechanism of Ir-catalyzed asymmetric hydrogenation of olefins with a strong coordinative carboxyl group and will likely inspire further catalyst design.