Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids.
Bowen LiZhiling WangYicong LuoHanlin WeiJianzhong ChenDelong LiuWanbin ZhangPublished in: Nature communications (2024)
Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for the preparation of chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, is still insufficient in both academic and industrial contexts. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of α-substituted acrylic acids affording the corresponding chiral α-substituted propionic acids with up to 99.4% ee (enantiomeric excess) and 10,000 S/C (substrate/catalyst). In particular, this method can be used to obtain (R)-dihydroartemisinic acid with 99.8:0.2 dr (diastereomeric ratio) and 5000 S/C, which is an essential intermediate for the preparation of the antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments and DFT (Density Functional Theory) calculations, which indicate that the protonolysis of the C-Ni bond of the key intermediate via an intramolecular proton transfer from the carboxylic acid group of the substrate, is the rate-determining step.
Keyphrases
- density functional theory
- transition metal
- molecular docking
- room temperature
- molecular dynamics
- metal organic framework
- ionic liquid
- reduced graphene oxide
- molecularly imprinted
- molecular dynamics simulations
- capillary electrophoresis
- highly efficient
- electron transfer
- heavy metals
- solid state
- plasmodium falciparum
- emergency department
- risk assessment
- medical students
- adverse drug
- energy transfer