Sly as Nicox: A palladium‐catalyzed addition of arylboronic acids to ketimines has been developed to efficiently provide products in up to 99 % yield and 96 % ee. The reactions could be run under ...aerobic conditions and with unpurified trifluoroethanol (TFE). A pyrrolidine compound bearing a chiral α‐tertiary amine was synthesized in several steps without loss of enantioselectivity. TFA=trifluoroacetate.
Asymmetric hydrogenation is one of the most powerful methods for the preparation of single enantiomer compounds. However, the chemo‐ and enantioselective hydrogenation of the relatively inert ...unsaturated group in substrates possessing multiple unsaturated bonds remains a challenge. We herein report a protocol for the highly chemo‐ and enantioselective hydrogenation of conjugated enynes while keeping the alkynyl bond intact. Mechanism studies indicate that the accompanying Zn2+ generated from zinc reduction of the CoII complex plays a critical role to initiate a plausible CoI/CoIII catalytic cycle. This approach allows for the highly efficient generation of chiral propargylamines (up to 99.9 % ee and 2000 S/C) and further useful chemical transformations.
The Co‐catalyzed chemo‐ and enantioselective hydrogenation of conjugated enynes has been realized for the synthesis of chiral propargylamines with high efficiency (up to 99.9 % ee and TON=2000). Mechanism studies indicate that the accompanying Zn2+ generated from zinc reduction of the CoII complex exhibits an activating effect for the initiation of the plausible CoI/CoIII catalytic cycle.
We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were ...easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.
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.
It's all in the solvent: An enantioselective variant of an aza‐Wacker‐type cyclization that gives isoindolinones containing tetrasubstituted carbon centers α to the nitrogen atom has been developed ...(see scheme; tfa=trifluoroacetate). The use of a highly coordinating solvent is crucial for the activity of the catalyst and the stereoselectivity the reaction (up to 99 % ee).
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.
A CoII/Box‐catalyzed Box=bis(oxazoline) enantioselective addition of potassium allyltrifluoroborate to cyclic ketimines was developed, providing the corresponding chiral α‐tertiary amines in high ...yields and with good enantioselectivity values. Alkoxycarbonyl‐ and alkyl‐substituted saccharin‐derived ketimines are suitable substrates for this allylation reaction. The product can be converted to complex molecules over several simple steps, including a precursor of MK‐0371, which is a kinesin spindle protein inhibitor. In addition, this catalytic system showed a strong positive nonlinear effect.
Co2+operation: A CoII/bis(oxazoline) (Box)‐catalyzed asymmetric allylation of cyclic ketimines was developed by using potassium allyltrifluoroborate. The desired homoallylic amines were obtained in excellent yields and enantioselectivity values (see scheme).
A switchable regioselective intramolecular aerobic aza-Wacker cyclization catalyzed by palladium is presented. Isoindolinones or isoquinolin-1(2H)-ones could be prepared selectively from the same ...substrates using different catalysts. The type and steric hindrance of the ligands may be the variables most significant for regiocontrol.
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.
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