Enantioselective Synthesis of Chiral β2-Amino Phosphorus Derivatives via Nickel-Catalyzed Asymmetric Hydrogenation

J Am Chem Soc. 2024 Dec 27. doi: 10.1021/jacs.4c10623. Online ahead of print.

Abstract

Compared with chiral β3-amino phosphorus compounds, which can be easily derived from natural optically pure α-amino acids, obtaining chiral β2-amino phosphorus derivatives remains a challenge. These derivatives, which cannot be derived from chiral natural amino acids, possess unique biological activities or potential catalytic activities. Herein, highly enantioselective hydrogenation for the preparation of chiral β2-amino phosphorus derivatives from E-β-enamido phosphorus compounds is reported by using a green and low-cost earth-abundant metal nickel catalyst (13 examples of 99% ee). In particular, this catalytic system provides the same enantiomer product from the E- and Z-alkene substrates, and the E/Z-substrate mixtures provide good results (up to 96% ee). The products can be diversely derivatized, and the derivatives exhibit good catalytic activities as novel chiral β2-aminophosphine ligands. Density functional theory calculations reveal that the weak attractive interactions between the nickel catalyst and the substrate are crucial for achieving perfect enantioselectivities. In addition, the different coordination modes between the E- or Z-substrates and the catalyst may result in the formation of the same enantiomer product.