Chemoselective Heterogeneous Hydrogenation of Sulfur Containing Quinolines under Mild Conditions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(9), P. 5864 - 5871

Published: Feb. 20, 2024

Sulfur, alongside oxygen and nitrogen, holds a prominent position as one of the key heteroatoms in nature medicinal chemistry. Its significance stems from its ability to adopt different oxidation states, rendering it valuable both polarity handle hydrogen bond donor/acceptor. Nevertheless, poisonous free electron pairs makes sulfur containing substrates inaccessible for many catalytic protocols. Strong (at low temperatures) irreversible chemisorption catalyst's surface is particular detrimental heterogeneous catalysts, possessing only few catalytically active sites. Herein, we present novel Ru-S catalyst that tolerates multiple functionalities, including thioethers, thiophenes, sulfoxides, sulfones, sulfonamides, sulfoximines, hydrogenation quinolines. The utility products was further demonstrated by subsequent diversifications functionalities.

Language: Английский

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Late-Stage Saturation of Drug Molecules

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(17), P. 11866 - 11875

Published: April 15, 2024

The available methods of chemical synthesis have arguably contributed to the prevalence aromatic rings, such as benzene, toluene, xylene, or pyridine, in modern pharmaceuticals. Many sp

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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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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Oxidative Dearomatization of Pyridines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2358 - 2363

Published: Jan. 17, 2024

Dearomatization of pyridines is a well-established synthetic approach to access piperidines. Although remarkably powerful, existing dearomatization processes have been limited the hydrogenation or addition carbon-based nucleophiles activated pyridiniums. Here, we show that arenophile-mediated dearomatizations can be applied directly introduce heteroatom functionalities without prior substrate activation. The arenophile platform in combination with olefin oxidation chemistry provides dihydropyridine cis-diols and epoxides. These previously elusive compounds are now readily accessible used for downstream preparation diversely functionalized

Language: Английский

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Recent Advances in Dearomative Partial Reduction of Benzenoid Arenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 14, 2024

Abstract Dearomative partial reduction is an extraordinary approach for transforming benzenoid arenes and has been well‐known many decades, as exemplified by the dehydrogenation of Birch hydroarylation Crich addition. Despite its remarkable importance in synthesis, this field experienced slow progress over last half‐century. However, a revival observed with recent introduction electrochemical photochemical methods. In Minireview, we summarize advancements dearomative arenes, including dihydrogenation, hydroalkylation, arylation, alkenylation, amination, borylation others. Further, intriguing utilization synthesis natural products also emphasized. It anticipated that Minireview will stimulate further arene transformations.

Language: Английский

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Photochemical dearomative skeletal modifications of heteroaromatics

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(12), P. 6600 - 6624

Published: Jan. 1, 2024

Dearomatization has emerged as a powerful tool for rapid construction of 3D molecular architectures from simple, abundant, and planar (hetero)arenes. The field evolved beyond simple dearomatization driven by new synthetic technology development. With the renaissance photocatalysis expansion activation mode, last few years have witnessed impressive developments in innovative photochemical methodologies, enabling skeletal modifications dearomatized structures. They offer truly efficient useful tools facile highly complex structures, which are viable natural product synthesis drug discovery. In this review, we aim to provide mechanistically insightful overview on these innovations based degree alteration, categorized into dearomative functionalization editing, highlight their utilities.

Language: Английский

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Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: March 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Language: Английский

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Transfer Hydrogenation of N- and O-Containing Heterocycles Including Pyridines with H₃N–BH₃ Under the Catalysis of the Homogeneous Ruthenium Precatalyst

Organic Letters, Journal Year: 2024, Volume and Issue: 26(4), P. 866 - 871

Published: Jan. 25, 2024

In this study, we report a transfer hydrogenation protocol that utilizes borane–ammonia (H3N–BH3) as the hydrogen source and commercially available RuCl3·xH2O precatalyst for selective aromatic reduction of quinolines, quinoxalines, pyridines, pyrazines, indoles, benzofurans, furan derivatives to form corresponding alicyclic heterocycles in good excellent isolated yields. Applications straightforward include efficient preparation useful key pharmaceutical intermediates, such donepezil flumequine, including biologically active compound.

Language: Английский

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Asymmetric Hydrogenation of Racemic 2-Substituted Indoles via Dynamic Kinetic Resolution: An Easy Access to Chiral Indolines Bearing Vicinal Stereogenic Centers

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5081 - 5087

Published: Feb. 15, 2024

The asymmetric hydrogenation (AH) of N-unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This has for years been limited 2/3-monosubstituted or 2,3-disubstituted indoles, which produce indolines bearing endocyclic centers. Herein, we have reported an innovative Pd-catalyzed AH racemic α-alkyl aryl-substituted indole-2-acetates using acid-assisted dynamic kinetic resolution (DKR) process, affording range structurally fascinating that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities. Mechanistic studies support the DKR process relies on rapid interconversion each enantiomer substrates, leveraged by acid-promoted isomerization between aromatic indole nonaromatic enamine intermediate. reaction can be performed gram scale, products derivatized into non-natural β-amino acids via facile debenzylation amino alcohol upon reduction.

Language: Английский

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