Chiral α-amino acids have applications, e.g., in pharmaceutical chemistry. Chiral α-aryl glycines, for example, are found in both bioactive natural products and synthetic drugs. They can be prepared, e.g., via a transition-metal-catalyzed asymmetric hydrogenation of α-aryl imino esters. However, existing methods for this type of reaction have drawbacks such as a limited substrate scope. Substrates with an easy-to-remove N–p-methoxyphenyl (PMP) protection group can help to overcome this limitation.

Wanbin Zhang, Shanghai Jiao Tong University, China, and colleagues have developed an efficient asymmetric hydrogenation of N-PMP imino esters for the synthesis of useful chiral α-aryl glycines (pictured), catalyzed by earth-abundant nickel. The team used Ni(OAc)₂·4H₂O as a catalyst, together with chiral ligands of the type (R,R)-BenzP* (BenzP* = 1,2-bis(t-butylmethylphosphino)benzene), to convert a variety of N-aryl imino esters into the corresponding chiral α-aryl glycines under 30 bar of H₂. Using amides instead of esters as substrates was also possible.

The desired products were obtained in high yields and with excellent enantioselectivities, and the reaction could be used on a gram scale. The chiral products can be easily deprotected and used for further transformations.

• Ni-catalyzed asymmetric hydrogenation of N-aryl imino esters for the efficient synthesis of chiral α-aryl glycines,
  Dan Liu, Bowen Li, Jianzhong Chen, Ilya D. Gridnev, Deyue Yan, Wanbin Zhang,
  Nat. Commun. 2020.
  https://doi.org/10.1038/s41467-020-19807-5