Nickel‐Catalyzed Asymmetric Hydrogenation of 2‐Amidoacrylates

Abstract

Earth‐abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2‐amidoacrylates, affording the chiral α‐amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α‐amino acids, β‐amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium‐labeling experiments and computational calculations.

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

“…Thus, the active chiral nickel hydride species has remained undetected, albeit several chiral diphosphine ligand nickel complexes have been well studies. In this study, at first, based on our previous studies of Ni catalysts 39,42 , the coordination behaviors of Ni salt and the ligand BenzP* were studied. Unlike previous investigations 39,42 (Fig.…”

“…To the best of our knowledge, there is still no Ni-catalyzed asymmetric hydrogenation of unactivated N-aryl imines. Continuing our pursuit of earth-abundant metal-catalyzed asymmetric hydrogenation 38,39,42 , herein we disclose an efficient Ni-catalyzed asymmetric hydrogenation of N-PMP imino esters for the synthesis of useful chiral α-aryl glycines (Fig. 1d).…”

“…1b) [28][29][30] . In view of current interest in the development of earthabundant metal catalysts in asymmetric hydrogenation [31][32][33][34][35][36][37][38][39][40][41] , which are inexpensive and environmentally friendly, the use of nickel has drawn increasing attention 24,[31][32][33][34][35][36][37][38][39][40][41] . Although Nicatalyzed asymmetric reduction has seen rapid development, the asymmetric hydrogenation of imines is still in its infancy 24,[42][43][44] .…”

Recent Developments in Transition-Metal-Catalyzed Asymmetric Hydrogenation of Enamides

“…This catalyst was found to be efficient for the asymmetric hydrogenation of 2-amidoacrylates, affording the corresponding chiral amino acid esters in yields of 90-93% and enantioselectivities of up to 96% (Scheme 39). 42 The reaction tolerated substrates with both electron-donating and electron-withdrawing substituents at the 2-, 3-and 4-positions of the aryl group as well as disubstituted, naphthyl and thienyl substrates. In addition, when the aryl group was changed to a cyclohexyl group, the hydrogenation proceeded smoothly to give the corresponding product with 93% ee, although the reacam scale.…”

“…Furthermore, the authors investigated the mechanism of the Ni-catalyzed reduction through deuterium-labeling experiments and computational calculations. 42 In 2018, Lv, Zhang and co-workers showed that the Ni(OAc) 2 /(S)-Binapine (L22) complex was an efficient catalyst for the asymmetric hydrogenation of -acetylamino vinylsulfones. The corresponding -amido sulfones were obtained with yields ranging from 75-95% and enantioselectivities of >99% using 5 mol% of the catalyst under 50 bar of…”