Determining the enantioselectivity of asymmetric hydrogenation through parahydrogen-induced hyperpolarization

Asymmetric hydrogenation plays an essential role for both academic research and industry to produce enantiomeric pure chiral molecules. Although nuclear magnetic resonance (NMR) is powerful in determining the yields of hydrogenation, it is still challenging to use NMR for chirality-related analysis. Herein, we applied parahydrogen-induced hyperpolarization (PHIP) NMR to determine the enantioselectivity of asymmetric hydrogenation and the absolute chirality of products. We hyperpolarized two types of unsaturated amino acid precursors, i.e., methyl-alpha-acetoamido cinnamate and (E)-ethyl 3-acetamidobut-2-enoate. Hydrogenation of prochiral substrates with parahydrogen gave temporary hyperpolarized diastereoisomers, which exhibit different PHIP patterns distinguishable in H-1 NMR. After assigning the NMR peaks by density functional theory calculations, we simulated the PHIP patterns of all the possible temporary hyperpolarized diastereoisomers and unambiguously assigned the chirality of the products and the enantioselectivity of asymmetric hydrogenation. Our work demonstrates the application and potential of PHIP in revealing the mechanism of asymmetric hydrogenation.

Automated summary

The use of PHIP NMR in determining the enantioselectivity of asymmetric hydrogenation and the absolute chirality of products has been demonstrated in this study. Through simulating the PHIP patterns of all possible temporary hyperpolarized diastereoisomers and assigning NMR peaks using density functional theory calculations, the chirality of products and the enantioselectivity of asymmetric hydrogenation were unambiguously determined. This work showcases the potential of PHIP in revealing the mechanism of asymmetric hydrogenation.