Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids

• DOI: 10.1038/s41467-024-49801-0
• Publication Date: 2024-07-07T19:01:18Z
• Authors: Bowen Li; Zhiling Wang; Yicong Luo; Hanlin Wei; Jianzhong Chen; Delong Liu; Wanbin Zhang
• Keywords: Science; Q; Article; 0104 chemical sciences

Abstract Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for preparation chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, still insufficient in both academic and industrial contexts. Herein, we report an nickel-catalyzed acrylic acids affording corresponding with up to 99.4% ee (enantiomeric excess) 10,000 S/C (substrate/catalyst). In particular, method can be used obtain ( R )-dihydroartemisinic acid 99.8:0.2 dr (diastereomeric ratio) 5000 S/C, which essential intermediate antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments DFT (Density Functional Theory) calculations, indicate that protonolysis C-Ni bond key intramolecular proton transfer from carboxylic group substrate, rate-determining step.