Ni-catalyzed asymmetric hydrogenation of N-aryl imino esters for the efficient synthesis of chiral α-aryl glycines

Abstract

Chiral α-aryl glycines play a key role in the preparation of some bioactive products, however, their catalytic asymmetric synthesis is far from being satisfactory. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of N-aryl imino esters, affording chiral α-aryl glycines in high yields and enantioselectivities (up to 98% ee). The hydrogenation can be conducted on a gram scale with a substrate/catalyst ratio of up to 2000. The obtained chiral N-p-methoxyphenyl α-aryl glycine derivatives are not only directly useful chiral secondary amino acid esters but can also be easily deprotected by treatment with cerium ammonium nitrate for further transformations to several widely used molecules including drug intermediates and chiral ligands. Formation of a chiral Ni-H species in hydrogenation is detected by ¹H NMR. Computational results indicate that the stereo selection is determined during the approach of the substrate to the catalyst.

Chiral α-amino acids find application in the fields of pharmaceutical, biological and synthetic chemistry. Here, the authors report a nickel-catalyzed asymmetric hydrogenation of N-aryl imino esters affording chiral α-aryl glycines in high yields and enantioselectivities.