Asymmetric arene hydrogenation: towards sustainability and application

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(15), P. 4996 - 5012

Published: Jan. 1, 2023

This review summarises the state-of-the-art in transition-metal catalysed asymmetric hydrogenation of (hetero)arenes and highlights recent advances with a special focus on sustainability while also addressing its shortcomings.

Language: Английский

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Enantioselective Synthesis of Chiral 1,4-Dihydroquinolines via Iridium-Catalyzed Asymmetric Partial Hydrogenation of Quinolines

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Chiral 1,4-dihydroquinolines are frequently found in natural products and pharmaceuticals, yet a generally useful route for their synthesis remains elusive. Here, we present an asymmetric partial hydrogenation strategy to access enantioenriched from quinolines. Our involves incorporating ester group at position 3 of the quinoline ring, thereby enhancing electronic deficiency polarity C3–C4 double bond. Employing chiral Ir-SpiroPAP catalyst facilitated wide variety 4-substituted 3-ethoxycarbonylquinolines, yielding high yields (up 95%) with exceptional enantioselectivity efficiency 99% ee 1840 TONs). Noteworthy its scalability practicality, method provides robust avenue valuable compounds such as 9-aryl aza-podophyllotoxins melatonin MT2 receptor modulators. Density functional theory calculations were performed gain insights into reaction mechanism origins enantioselectivity.

Language: Английский

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Dynamic Kinetic Resolution-Based Asymmetric Transfer Hydrogenation of Racemic 2-Substituted Quinolines

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic centers, the selective construction both endo- and exo-cyclic centers remains a challenge that requires further development. This study introduces dynamic kinetic resolution (DKR)-based transfer hydrogenation racemic 2-substituted quinolines, which yields structurally novel consecutive excellent stereoselectivities (59 examples, generally >20:1 dr >90% ee, up three stereocenters). Our approach offers mechanistically method for asymmetric transformation electron-deficient aromatic N-heterocycles presents an innovative way expand N-heterocycle chemical space chemistry.

Language: Английский

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Cobalt-Catalyzed Asymmetric Dearomative [3 + 2] Annulation of Quinolines, Isoquinolines, and Pyridines

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(17), P. 11528 - 11540

Published: Aug. 16, 2023

A highly enantioselective dearomative [3 + 2] annulation of quinolines, isoquinolines, and pyridines with donor–acceptor aminocyclopropanes was achieved. With C1-symmetric imidazoline-pyrroloimidazolone pyridine as the tridentate ligand Co(OTf)2 Lewis acid, diverse chiral indolizidine benzo-fused derivatives were obtained in good yields (up to 98% yield), excellent diastereoselectivities (>20:1 dr), enantioselectivities ee). Mechanistic experiments density functional theory (DFT) calculations revealed that nitrogen acted a bifunctional ligand. The not only coordinated Co(II) salt activate aminocyclopropane via bidentate coordination, but also formed H-bond oxygen atom succinimide moiety fix orientation aminocyclopropane, thus facilitating nucleophilic attack N-heteroaromatics. Additionally, high enantioselectivity reaction governed by steric factors.

Language: Английский

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Enantiodivergent Hydrogenation of Exocyclic α,β‐Unsaturated Lactams Enabled by Switching the N‐Chirality of Iridium Catalyst

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(11)

Published: Jan. 11, 2023

Central chirality is an important chiral element used in the design of ligands and catalysts. Mostly, attention organic chemists focused on developing with stable stereogenic centers. However, N-chirality ligand has been rarely explored due to its flexibility. Here we demonstrate design, synthesis, application a class simple P,N-ligands flexible their derived iridium complexes fixed N-chiral stereocenters. Both configurations N-stereocenter could be selectively formed from same ligand. This pair diastereoisomeric showed good performance enantiodivergent asymmetric hydrogenation exocyclic α,β-unsaturated lactams. The N-H group plays impressive role catalytic activity. Computational studies emphasized importance group.

Language: Английский

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Rhodium‐Catalyzed Asymmetric Hydrogenation of 3‐Benzoylaminocoumarins for the Synthesis of Chiral 3‐Amino Dihydrocoumarins

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(44), P. 23602 - 23607

Published: Oct. 1, 2021

An asymmetric hydrogenation of 3-benzoylaminocoumarins was achieved for the first time using our BridgePhos-Rh catalytic system, providing chiral 3-amino dihydrocoumarins in high yields (up to 98 %) and with excellent enantioselectivities 99.7 % ee). The relationship between hydrogenations dihedral angles resulting π-π stacking effects complexes, which were determined by X-ray diffraction analysis, are discussed. corresponding hydrogenated products allow many transformations, several skeletons important physiological pharmacological activities.

Language: Английский

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Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinonesviaRh–thiourea catalyzed asymmetric hydrogenation

Chemical Science, Journal Year: 2023, Volume and Issue: 14(34), P. 9024 - 9032

Published: Jan. 1, 2023

Chiral tetrahydroquinoxalines and dihydroquinoxalinones represent the core structure of many bioactive molecules. Herein, a simple efficient Rh-thiourea-catalyzed asymmetric hydrogenation for enantiopure was developed under 1 MPa H2 pressure at room temperature. The reaction magnified to gram scale furnishing desired products with undamaged yield enantioselectivity. Application this methodology also conducted successfully continuous flow conditions. In addition, 1H NMR experiments revealed that introduction strong Brønsted acid, HCl, not only activated substrate but established anion binding between ligand. More importantly, chloride ion facilitated heterolytic cleavage dihydrogen regenerate active dihydride species which computed be rate-determining step. Further deuterium labeling density functional theory (DFT) calculations demonstrated underwent plausible outer-sphere mechanism in new catalytic transformation.

Language: Английский

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Earth-Abundant Heterogeneous Cobalt Catalyst for Selective Ring Hydrogenation of (Hetero)arenes and Gram-Scale Synthesis of Pharmaceutical Intermediates

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(14), P. 9724 - 9744

Published: July 10, 2023

It is highly desired but scientifically as well technologically challenging to develop non-noble metal-based hydrogenation catalysts that can substitute noble ones. Herein, we present a facile and environmentally friendly approach for synthesizing pine needle biomass-derived nitrogen-doped carbon-supported Co3O4 nanoparticles (Co3O4/PNC). The whole process involves the impregnation of needles with cobalt nitrate salt subsequent pyrolysis at 500 °C under nitrogen atmosphere. Applying this Co3O4/PNC nanocatalyst, broad range substituted phenols functional organic chemicals, including N- O-heteroarenes, could be efficiently transformed into their corresponding ring-hydrogenated products in good-to-excellent yields (>55 examples). In addition, catalytic has proved useful preparation seven key drug intermediates on gram scale, which are commonly used manufacturing active pharmaceutical ingredients bulk quantities. Advantageously, cyclohexanecarboxylic acid, building block praziquantel, was synthesized from polystyrene two-step process. pivotal physicochemical properties fresh spent nanocatalysts were thoroughly investigated by high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, diffraction, N2 adsorption–desorption, Raman analysis, H2-temperature programmed reduction, CO2-temperature-programmed desorption analysis. content nanocatalyst estimated inductively coupled plasma atomic emission spectroscopy Besides, stable, easily recovered, reused effectively four cycles no loss activity or selectivity. Furthermore, density theory calculations performed get more insights reaction mechanism.

Language: Английский

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A review on solvent-controlled stereodivergent catalysis

Tetrahedron, Journal Year: 2023, Volume and Issue: 150, P. 133754 - 133754

Published: Nov. 25, 2023

Language: Английский

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Design Approaches That Utilize Ionic Interactions to Control Selectivity in Transition Metal Catalysis

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

The attractive force between two oppositely charged ions can constitute a powerful design tool in selective catalysis. Enzymes make extensive use of ionic interactions alongside variety other noncovalent interactions; recent years have seen synthetic chemists begin to seriously explore these catalyst designs that also incorporate reactive transition metal. In isolation, single interaction exhibits low directionality, but many successful systems they exist additional which provide high degree organization at the selectivity-determining state. Even situations with key interaction, directionality is not always detrimental, and even be advantageous, conferring generality catalyst. This Review explores approaches utilize control selectivity metal It divided into halves: first, occurs outer sphere complex, using ligand or bound an anion; second, bears formal charge, associated counterion.

Language: Английский

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