An efficient nickel‐catalyzed asymmetric hydrogenation of N‐tBu‐sulfonyl imines was developed with excellent yields and enantioselectivities using (R,R)‐QuinoxP* as a chiral ligand. The use of a much ...lower catalyst loading (0.0095 mol %, S/C=10500) represents the highest catalytic activity for the Ni‐catalyzed asymmetric hydrogenations reported so far. Mechanistic studies suggest that a coordination equilibrium exists between the nickel salt and its complex, and that excess nickel salt promotes the formation of the active Ni‐complex, and therefore improved the efficiency of the hydrogenation. The catalytic cycle was also investigated by calculations to determine the origin of the enantioselectivity. An extensive network of numerous weak attractive interactions was found to exist between the catalyst and substrate in the transition state and may also contribute to the high catalytic activity.
The first Ni‐catalyzed asymmetric hydrogenation of N‐sulfonyl imines using H2 gas as a hydrogen source has been realized with excellent enantioselectivity. The presence of an excess of the nickel salt, with respect to the ligand, promotes the formation of the active Ni catalyst. The reaction features a wide substrate scope, low catalyst loading, and convenient removal of the protecting group.
The mechanism of the recently reported catalyzed asymmetric hydrogenation of enyne
catalyzed by the Co-(
,
)-QuinoxP* complex was studied by DFT. Conceivable pathways for the Co(I)-Co(III) mechanism ...were computed together with a Co(0)-Co(II) catalytic cycle. It is commonly assumed that the exact nature of the chemical transformations taking place along the actually operating catalytic pathway determine the sense and level of enantioselection of the catalytic reaction. In this work, two chemically different mechanisms reproduced the experimentally observed perfect stereoselection of the same handedness. Moreover, the relative stabilities of the transition states of the stereo induction stages were controlled via exactly the same weak disperse interactions between the catalyst and the substrate.
Chiral hydroxylamines are vital substances in bioscience and versatile subunits in the preparation of a variety of functional molecules. However, asymmetric and non-asymmetric synthetic approaches to ...these compounds are far from satisfactory. Although atom-economic metal-catalysed asymmetric hydrogenations have been studied for over 50 years, the asymmetric hydrogenation of oximes to the corresponding chiral hydroxylamines remains challenging because of the labile N-O bond and inert C=N bond. Here we report an environmentally friendly, earth-abundant, transition-metal nickel-catalysed asymmetric hydrogenation of oximes, affording the corresponding chiral hydroxylamines with up to 99% yield, 99% e.e. and with a substrate/catalyst ratio of 1,000. Computational results indicate that the weak interactions between the catalyst and substrate play crucial roles not only in the transition states, but also during the approach of the substrate to the catalyst, by selectively reducing the reaction barriers and thus improving the reaction efficiency and securing the generation of chirality.
An efficient cobalt‐catalyzed asymmetric hydrogenation of C=N bonds has been realized. Chiral hydrazines were obtained in high yields and with excellent enantioselectivities (95–98 % ee). The ...hydrogenation went smoothly at up to 2000 substrate/catalyst and on a gram scale. The success of this reaction relies on the presence of an NHBz group in the substrates, with the reactivity and enantioselectivity improved by an assisted coordination to the cobalt atom and a nonbonding interaction with the ligand. Furthermore, this reaction has practical applications for the synthesis of several useful chiral nitrogen‐containing compounds.
Interaction skills: Chiral nitrogen‐containing compounds have been synthesized with excellent enantioselectivity (95–98 % ee) and high productivity (up to 2000 TON) by the Co‐catalyzed asymmetric hydrogenation of C=N bonds. The reaction is facilitated by coordination of an NHBz group in the substrates to the cobalt atom and a nonbonding interaction with the ligand.
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.
An asymmetric hydrogenation of 2‐amidoacrylates using a catalyst based on earth‐abundant nickel has been developed. The hydrogenated products are obtained with excellent enantioselectivity (up to 96 % ee) and high catalytic efficiency (S/C up to 2000) and can be simply converted into chiral α‐amino acids and β‐amino alcohols.
The mechanism of the asymmetric hydrogenation of exocyclic α,β‐unsaturated carbonyl compounds with the (aS)‐Ir/iPr‐BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. ...Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values.
H in a fix: The title studies show an equilibrium of dinuclear iridium hydrides at low temperature after hydrogenation of the precatalyst. Computations of the conceivable R and S pathways allowed elucidation of the mechanism for enantioselection, thus affording computed optical yields which are consistent with the experimental values. The structure S1 features hydrogen bonding between the catalyst and the carbonyl group of the substrate.
Global reaction route mapping (GRRM) analysis for compounds with the formula C4H5NO allowed for the detection of the corresponding “Guinness molecules” 000 and 001, as well as around 150 other stable ...minima of the same composition. The results suggest that compounds of similar functionality form a kind of “Stability Island” with their free energies of formation falling within s relatively limited range.
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
H NMR. Computational results indicate that the stereo selection is determined during the approach of the substrate to the catalyst.
Allylic alcohols were directly used in Pd‐catalyzed allylic alkylations of simple ketones under mild reaction conditions. The reaction proceeded smoothly at 20 °C by the concerted action of a Pd ...catalyst, a pyrrolidine co‐catalyst, and a hydrogen‐bonding solvent, and does not require any additional reagents. A computational study suggested that methanol plays a crucial role in the formation of the π‐allylpalladium complex by lowering the activation barrier.
Concerted action: Allylic alcohols were directly used in the title reaction under mild conditions. The reaction smoothly proceeds by the concerted action of a Pd catalyst, a pyrrolidine co‐catalyst, and a hydrogen‐bonding solvent, and does not require any additional reagents. A computational study suggested that methanol plays a crucial role in the formation of the π‐allylpalladium complex by lowering the activation barrier.
An efficient copper-catalyzed reductive defluorination of β-trifluoromethylated enones via an oxidative homocoupling of Grignard reagents is reported. The reaction proceeded smoothly with a wide ...range of substrates, including the ones bearing aromatic heterocycles, such as furyl and thienyl ring systems in high yields (80–92%, except one example) under mild conditions. This provides a practical method for synthesis of gem-difluoroolefin ketones. It is also worth noting that this homocoupling process of Grignard reagents using β-trifluoromethylated enones as “oxidizing reagents” is effective for both the Csp2–Csp2 and Csp3–Csp3 bond formations, including for substrates whose β-hydride elimination of the corresponding transition metal alkyl complex is particularly facile, affording coupling products with high yields (83–95%), simultaneously.
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