Design and numerical simulation of an new asymmetric variable-clearance scroll hydrogen circulation pump profile

We report a practical one-pot protocol for accessing chiral dihydroisobenzofurans via tandem asymmetric hydrogenation and selective 5-exo-dig oxo-cyclization. This method displays high activity (up to 99% yield and S/C = 2000:1) and excellent selectivity (up to 99% ee and exclusive Z selectivity) across a broad substrate scope. Scale-up reactions and further transformations afforded challenging derivatives bearing cis-1,3-stereogenic centers. The operational simplicity and high efficiency arise from the synergistic dual roles of the metal and base.

Chiral γ-lactams represent an important class of five-membered nitrogen-containing heterocyclic scaffolds, widely found in natural products and bioactive drug molecules. Although multiple strategies exist for constructing this scaffold, asymmetric catalytic hydrogenation is regarded as the most direct and efficient approach owing to its atom economy and step simplicity. Here, we report a Rh/bisphosphine-thiourea catalytic system successfully applied to the asymmetric hydrogenation of various N-substituted α,β-unsaturated γ-lactams, including chiral amino acid derivatives. Excellent enantioselectivity (up to 99% ee and 99:1 dr) and exceptionally high turnover numbers (TON up to 3000) were achieved. The method has been successfully applied to the gram-scale synthesis of key intermediates for pharmaceutically relevant compounds, including brivaracetam, (R)-pregabalin, and (R)-baclofen, demonstrating its potential for application in pharmaceutical manufacture.

Magnetic field enhancement represents an effective strategy to promote electrocatalytic water splitting, yet the mechanistic origin of asymmetric hydrogen evolution reaction (HER)/oxygen evolution reaction (OER) promotion remains poorly understood. Here, we investigate a bifunctional Fe0.5Rh0.5 (FeRh) single-crystal thin-film catalyst and demonstrate distinct asymmetric activity improvement under a 13 kOe magnetic field, ∼40% enhancement for HER and ∼32% for OER. Density functional theory and spin-resolved electronic structure analysis reveal that the field raises spin polarization by 1.2%, enhances density of states near the Fermi level, and accelerates interfacial charge transfer. The asymmetric enhancement stems from a more significant Gibbs free energy reduction for H adsorption than for OH**. Moreover, FeRh follows the oxide pathway mechanism to avoid excessive surface oxyhydroxide passivation, ensuring a stable magneto-responsive catalysis. This work clarifies the fundamental mechanism of asymmetric magnetic field promotion and provides a rational design for magnetically enhanced bifunctional electrocatalysts.

A high sensitivity strategy to screen NAD(P)H-dependent reductase activity by coupled enzyme cascade.

Metabolic engineering of Saccharomyces cerevisiae for efficient production of dihydroartemisinic acid.

Carbocation rearrangement is a powerful tool for converting a simple precursor into a complex molecular scaffold. However, controlling the stereoselectivity of a reaction that involves carbocation rearrangement is challenging and remains elusive. In this study, we demonstrate a novel iridium-catalyzed Wagner-Meerwein rearrangement and asymmetric hydrogenation of carbocation precursors (1-(aryl)-1-(1-methylcyclobutyl/cyclopentyl) ethan-1-ol) for the synthesis of various optically active gem-dimethyl cycloalkanes. Hence, enantiopure gem-dimethyl-containing compounds are important motifs found in many natural products, and some are FDA-approved drugs. Our methodology starts with an iridium-catalyzed formal deoxygenation of tertiary alcohols to generate a tertiary carbocation that triggers the Wagner-Meerwein rearrangement via the ring expansion and alkyl migration cascade to furnish a stable tertiary-benzyl carbocation. Sequential olefination and in situ asymmetric hydrogenation provide access to various gem-dimethyl chiral cycloalkanes in excellent yield (> 99%) and enantioselectivity (ee up to > 99%). Otherwise, establishing a high yield and enantioselectivity in a saturated cyclic hydrocarbon next to a sterically hindered gem-dimethyl group would not be possible by conventional methods.

An optimized approach to the multigram synthesis of [(1R,2R,3S)-(+)-1,2-dimethyl-2,3-bis(diphenylphosphinomethyl)cyclopentyl]methanol (ROCKYPhos, CatASium I®), a camphor-derived chiral diphosphine ligand, has been developed. The key improvement in the synthetic scheme involved the oxidative cleavage of 3,9-dibromocamphor with V2O5 – HNO3 or NH4VO3 – Cu(NO3)2 – HNO3 system, which gave the corresponding dicarboxylic acid in the yield of 28% and significantly reduced the reaction sequence. The NMR study of a diselenide derivative of ROCKYPhos showed that one of the PPh2 groups had strong donor properties comparable to those of trialkylphosphines. The asymmetric hydrogenation of N-acetyl-1,2-dihydroisoquinoline-4-carboxylates in the presence of ROCKYPhos provided target tetrahydroisoquinolines with up to 52% ee – an outstanding result for this substrate class.

In this paper, we report a macrocyclic alkene-derived borane catalyst for the asymmetric hydrogenation of imines. A wide range of imines was successfully converted to chiral amines in 80-97% yields and 40-97% ee. The macrocyclic framework is indispensable for excellent catalytic activity and enantioselectivity. A gram-scale reaction with 0.2 mol % catalyst loading achieved a turnover number of 485, the highest reported to date for frustrated Lewis pair-catalyzed asymmetric imine hydrogenation.

ABSTRACT The iridium complexes of PNO‐type ligands containing phenolic hydroxyl groups have been successfully applied to the asymmetric hydrogenation of various amino ketones bearing strong coordinating N atoms. A series of chiral β ‐ or γ ‐amino alcohols were obtained with up to > 99% yields and > 99% ee. The gram‐scale experiments have been conducted with S/C = 10,000, and the resulting products (93%–96% yields and 97%–98% ee) could be further applied in the treatment of hypotension caused by shock or anesthesia ( R )‐Phenylephrine, antidepressant drugs, or potential analgesic agents ( S )‐duloxetine, ( R )‐fluoxetine, and ( R )‐atomoxetine. Additionally, based on the previous reports, control experiments, and DFT calculations, we proposed a possible transition state model for enantioselective hydrogenation involving alkali metal cations. The alkali cation (Li + , Na + , and K + ) can polarize the carbonyl of the ketone, which promotes the carbonyl carbon hydrogenation. This catalytic system exhibits high catalytic efficiency and excellent tolerance of substrates (up to 58 examples). Moreover, the solvent EtOH and the base NaOH used are both inexpensive and suitable for industrial applications. This protocol verified the practicality of the Ir‐f‐Amphbinol in the asymmetric hydrogenation of various α ‐ or β ‐amino ketones. The mechanism research provides certain theoretical guidance for the design and synthesis of novel and highly efficient catalysts for asymmetric hydrogenation.

Achieving stereocontrol over two remote, flexible P- and C-stereocenters with a single catalyst remains a formidable challenge in the construction of chiral phosphines. We herein report a manganese-catalyzed enantioconvergent hydrophosphination of racemic allylic alcohols via a borrowing hydrogen (BH) strategy. This approach utilizes a single tailored Mn catalyst to orchestrate a cascade of dehydrogenation, enantioconvergent P-H addition, and asymmetric hydrogenation. This method provides direct access to P,C-stereogenic γ-hydroxy phosphines with excellent enantio- and diastereoselectivity, offering an atom-economical and sustainable route to diverse, high-value chiral phosphine libraries.

An efficient and enantioselective Ir/Huaphos-catalyzed asymmetric hydrogenation system has been developed for the dynamic kinetic resolution (DKR) of aryl α-chloro-β-keto esters, furnishing anti-α-chloro-β-hydroxy esters in >99% ee and 98:2 dr at an exceptional substrate-to-catalyst ratio (S/C = 20,000). The same system also enables asymmetric hydrogenation of aryl alkyl ketones, delivering chiral 1-aryl aliphatic alcohols in up to 99% yield and >99% ee. Gram-scale syntheses of key intermediates to diltiazem and aprepitant further demonstrate the utility of this method for the highly stereoselective preparation of valuable chiral building blocks.

Herein, we report a simple, one-pot, scalable process for the preparation of a series of enamides, which were subsequently hydrogenated with high efficiency and excellent enantioselectivity to the corresponding chiral amides using the Rh-ZhangPhos catalyst. This methodology is practical and facilitates easy postreaction handling, with the hydrogenation providing nearly perfect stereoselectivity. DFT studies uncovered distinct rate-determining steps for competing enantiomeric pathways: migrational insertion for the major product and reductive elimination for the minor product, challenging conventional assumptions of a unified mechanistic origin. Noncovalent interaction analysis, particularly steric repulsion in the reductive elimination step, offers a theoretical rationale for long-standing empirical strategies in bisphosphine ligand design, bridging experiment, and computation in asymmetric hydrogenation.

A cobalt pincer complex has been designed, synthesized, and successfully applied to catalytic asymmetric hydrogenation of quinolines under mild conditions. Containing a PNN ligand that features both a P and a C-stereogenic center, the cobalt catalyst allows for the hydrogenation of a variety of quinolines to afford chiral 1,2,3,4-tetrahydroquinolines with high yields and excellent enantioselectivities in general (51 examples, up to 99.9% ee). Probe reactions and DFT calculations suggest that the hydrogenation proceeds via a stepwise 1,2-1,2-hydride transfer pathway. The results obtained could provide a valuable hint for the development of more efficient 3d transition metal catalysts for asymmetric catalysis.

An improved synthesis of manganese(I) tricarbonyl complexes of the Phosphino‐Ferrocenyl‐Amino‐Methyl‐Pyridine (PFAMPy) ligand family is reported. A comparison of both the neutral form [Mn(PFAMPy)(CO) 2 Br] and the cationic form [Mn(PFAMPy)(CO) 3 ]Br was made for an enantioselective ketone hydrogenation, with both catalysts giving high yields and enantiomer ratios over 98:2. The [Mn(PFAMPy)(CO) 3 ]Br catalyst was then applied in tandem conjugate reduction‐ester hydrogenation to convert cinnamate esters into aryl propanols. This could be achieved for disubstituted cinnamates with the problematic inseparable allyl alcohol side products almost eliminated below 0.5%. A strategy to prevent CO bond reduction preceding CC reduction, and hence allylic alcohol side products, is to use a tert ‐butyl ester and mild conditions for the first few hours of reaction, prior to increasing temperature to promote ester hydrogenation. This approach is needed for trisubstituted cinnamate esters, which otherwise give mixtures. It is possible to carry out just conjugate reductions to saturated esters at lower temperatures without significant ester hydrogenation. Examples of manganese‐catalyzed asymmetric hydrogenation of alkenes are presented in the form of an enantioselective and chemoselective conjugate reduction of trisubstituted cinnamate esters.

New chiral bidentate phosphine-aminophosphine ligands based on a pentane-2,4-diyl backbone, with the general formula Ph2PCH(CH3)CH2CH(CH3)N(R1)PR22 (R1 = Me, Et, nPr, nBu, iPr; R2 = Ph, Cy), have been developed and applied in the copper-catalyzed asymmetric hydrogenation of simple ketones. The addition of achiral monodentate phosphines as co-ligands significantly enhanced both catalytic turnover and enantioselectivity. It was observed that the steric properties of the ligands predominantly influence catalytic activity and enantioinduction, whereas their electronic characteristics play a secondary role. Comprehensive screening of reaction conditions, including variation of the metal source and careful selection of both chiral and achiral ligands with appropriately tuned stereochemistry, enabled the hydrogenation to proceed with low catalyst loadings (0.5 mol%) while maintaining high yields and enantioselectivities (up to 92% ee) across a broad substrate scope. Based on experimental findings and relevant literature precedents, a mechanistic proposal is presented to explain the observed reactivity trends.

Earth-abundant manganese-catalyzed asymmetric hydrogenation has emerged as a sustainable alternative to noble metal systems, achieving remarkable success in the reduction of polar C═O, C═N, and heteroaromatic substrates. However, because the polar and nucleophilic Mn-H species are inherently mismatched with nonpolar C═C bonds, asymmetric hydrogenation of C═C bonds with manganese catalysts remains a challenging and unexplored area. Herein, we disclose the first manganese-catalyzed asymmetric hydrogenation of electron-deficient polarized olefins enabled by an efficient metal-ligand cooperation process utilizing 2-hydroxypyridine-oxazoline ligands. This strategy delivers a broad range of substrates with up to 99% yield with 98% enantiomeric excess. Moreover, this catalytic system enables the hydrogenation kinetic resolution of racemic 4-aryl-quinolin-2-ones, affording axial-chiral recovered substrates with selectivity factor up to 178. These results pave up a new platform for manganese-catalyzed asymmetric hydrogenation, expanding the scope of earth-abundant metal catalysis in enantioselective synthesis.

Ruthenium(II)-catalyzed asymmetric transfer hydrogenation for enantioselective synthesis of (S)-/(R)-4-ethyl-N-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]benzamide exhibiting differing antinociceptive effects.

Efficient asymmetric hydrogenation of 2-pyridyl cyclic imines enabled by a novel hybrid diphosphine ligand

Synthesis of chiral P,S ferrocenyl ligands for catalyst heterogenization and testing in the homogeneous asymmetric hydrogenation of acetophenone