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.

Nickel-Catalyzed Enantioselective α-Alkenylation of N-Sulfonyl Amines: Modular Access to Chiral α-Branched Amines

“…First, in the presence of a stoichiometric amount of nickel catalyst, 1a was converted to imine 10a (45% combined yield with corresponding aldehyde 10b ) along with unreacted 1a . We also observed a Ni-hydride species by 1 H NMR spectroscopy . Moreover, in the presence of alkyne 2b , besides imine (aldehyde), alkene 11a/b formed.…”

“…We also observed a Ni-hydride species by 1 H NMR spectroscopy. 68 Moreover, in the presence of alkyne 2b, besides imine (aldehyde), alkene 11a/b formed. Given that the oxidative addition of Ni(0) into a N−H bond has been reported, 69 the above-described results suggest that the amine is converted to an imine by an oxidative addition/β-H elimination process.…”

Mechanism of Potassiumtert-Butoxide-Catalyzed Ketones Hydrogenation in the Solution Phase

“…Besides the interest in mechanistic aspects such as new modes of hydrogen activation, the following practical aspects and expectations are most often mentioned for the motivation to develop transition non-noble metal catalysis: decreased cost and increased abundance of a metal, reduced metal toxicity, and possible different reactivity of non-noble metals . Although most of the developed transition non-noble homogeneous catalysts are not (yet) competitive for synthetic, and much less for industrial, applications, the field is undergoing active development. − …”

Reduction of Amides to Amines with Pinacolborane Catalyzed by Heterogeneous Lanthanum Catalyst La(CH2C6H4NMe2-o)3@SBA-15

“…Amine functional groups are versatile and important structural motifs that are widely found in fine and bulk chemicals, pharmaceuticals, and agrochemicals. − Amines are usually obtained through synthetic methodologies such as reductive amination, − alcohol amination, − hydroamination, − and transamination. − In comparison, deoxygenative reduction of amides is believed to be a more favorable synthetic strategy due to the prevalence of amides in nature and availability by synthetic approaches . However, the reduction of amides to amines is a great challenging task due to the high thermodynamic stability and the low electrophilicity of the resonance-stabilized carboxamide moieties .…”