The Implications of the Brønsted Acidic Properties of Crabtree-Type Catalysts in the Asymmetric Hydrogenation of Olefins

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(36), P. 16252 - 16261

Published: Aug. 31, 2022

Chiral iridium complexes derived from Crabtree's catalyst are highly useful in modern hydrogenations of olefins attributed to high reactivity, stereoselectivity, and stability. Despite that these precatalysts pH neutral, the reaction mixtures turn acidic under hydrogenation conditions. This Perspective is devoted implications intrinsic Brønsted acidity catalytic intermediates asymmetric olefins. has often been used only as a rationale for side-product formation, more recent methodologies have started use this property advantageously. We hope serves stimulant development such compelling new hydrogenations. The inherent scientific opportunities utilizing or annihilating generated acid enormous, potential innovations outlined toward end.

Language: Английский

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Homogeneous Catalytic Hydrogenation of C=C and C≡C

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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One‐Pot Synthesis of Chiral Succinate Dehydrogenase Inhibitors and Antifungal Activity Studies

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract In this work, a series of novel chiral succinate dehydrogenase inhibitors (SDHIs) are synthesized through one‐pot Rh‐catalyzed asymmetric hydrogenation‐condensation strategy. This method exhibits high efficiency (up to 1000 Ton, 94% yield over two steps), stereoselectivity 99% ee), and broad substrate scope (68 examples in total), providing superior pathway for the synthesis such fungicides. Mechanistic studies indicate that amino group at 2‐position phenyl ring acts as an activating group, enhancing reactivity control reaction. Furthermore, these molecules exhibit broad‐spectrum highly effective antifungal biological activity. Notably, enantiomers show significant differences both vitro vivo fungi‐inhibiting experiments. Especially, ( S )‐ 5f showcases activity against Botrytis cinerea (EC 50 = 0.48 µ m ) is much higher than its R enantiomer 36.7 ). Molecular docking calculations, molecular dynamic simulation, enzyme assays, ligand‐target interaction experiments demonstrate (ΔG MM‐PBSA −18.86 kcal mol −1 , K D 6.04 inhibits more effectively −13.01 8.5 Moreover, have significantly different effects on spore germination destruction fungal phenotype.

Language: Английский

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Thermodynamic Network Cards of Hantzsch Ester, Benzothiazoline, and Dihydrophenanthridine Releasing Two Hydrogen Atoms or Ions on 20 Elementary Steps

The Journal of Organic Chemistry, Journal Year: 2020, Volume and Issue: 85(19), P. 12535 - 12543

Published: Sept. 3, 2020

In this work, thermodynamic driving forces on 20 possible elementary steps of Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydrophenanthridine (PDH2) releasing two hydrogen atoms or ions were measured derived from the related data using Hess' law in acetonitrile. Furthermore, network cards HEH2, BTH2, PDH2 first established. Based cards, hydride-donating, hydrogen-atom-donating, electron-donating abilities XH2 XH-, hydrogen-atom(ion)-donating are discussed detail. Obviously, not only offer rational guidance for organic synthetic chemists to properly choose an appropriate reducer among three reducing agents hydrogenate various unsaturated compounds but also strongly promote elucidatation detailed hydrogenation mechanisms.

Language: Английский

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Azole‐Directed Cobalt‐Catalyzed Asymmetric Hydrogenation of Alkenes

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(44)

Published: May 27, 2022

The azole-directed cobalt-catalyzed asymmetric hydrogenation of alkenes has been developed with high efficiency. With this approach, chiral pyrazole compounds were obtained in quantitative yields and excellent enantioselectivities (up to 99 % ee) under mild conditions, the was conducted on a gram scale up 2000 TON. Several useful applications demonstrated including convenient introduction β-chirality drug intermediate containing an azole ring.

Language: Английский

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Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2-Substituted Cyclopentyl Aryl Ketones

Precision Chemistry, Journal Year: 2023, Volume and Issue: 1(3), P. 146 - 152

Published: Feb. 10, 2023

Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic. Herein, we report efficient iridium-catalyzed asymmetric α,β-unsaturated ketones for the synthesis chiral 2-substituted cyclopentyl aryl ketones, structural motif preparation pharmaceuticals and bioactive molecules. The reaction proceeded very well with good functional group compatibility delivered hydrogenated products in high yields stereoselectivities (up to 99% yield, >20:1 dr ee). In addition, could be carried out on a gram-scale, all four stereoisomers bearing two contiguous stereocenters were obtained. Furthermore, product can transformed into ERβ agonist Erteberel, pathway was also studied via deuterium-labelling experiments.

Language: Английский

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Enantioselective Carboetherification/Hydrogenation for the Synthesis of Amino Alcohols via a Catalytically Formed Chiral Auxiliary

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(41), P. 17334 - 17339

Published: Oct. 2, 2020

Chiral auxiliaries and asymmetric catalysis are the workhorses of enantioselective transformations, but they still remain limited in terms either efficiency or generality. Herein, we present an alternative strategy for controlling stereoselectivity chemical reactions. Asymmetric is used to install a transient chiral auxiliary starting from achiral precursors, which then directs diastereoselective We apply this palladium-catalyzed carboetherification/hydrogenation sequence on propargylic amines, providing fast access enantioenriched amino alcohols, important building blocks medicinal chemistry drug discovery. All stereoisomers product could be accessed by choice ligand substituent amine, leading stereodivergent process.

Language: Английский

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Design of oxa-spirocyclic PHOX ligands for the asymmetric synthesis of lorcaserin via iridium-catalyzed asymmetric hydrogenation

Chemical Communications, Journal Year: 2020, Volume and Issue: 57(2), P. 195 - 198

Published: Nov. 14, 2020

A series of highly rigid oxa-spiro phosphine–oxazoline ligands (O-SIPHOX) were synthesized efficiently, their iridium complexes showed high reactivity and enantioselectivity in the synthesis key intermediate anti-obesity drug lorcaserin.

Language: Английский

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Rhodium-Catalyzed Highly Enantioselective Hydroboration of Acyclic Tetrasubstituted Alkenes Directed by an Amide

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(23), P. 16194 - 16202

Published: June 4, 2024

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, tetrasubstituted with high diastereo- enantioselectivities continues as an unmet challenge since 1950s due to its extremely low reactivity difficulties simultaneously control regio- stereoselectivity a alkene. Here, we report highly regio-, diastereo-, catalytic diverse acyclic alkenes. The delicate interplay electron-rich rhodium complex coordination-assistance forms adaptive catalyst that effectively overcomes controls stereoselectivity. generality system is exemplified by efficacy across various steric electronic properties.

Language: Английский

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Asymmetric Synthesis of the cis-1,2-Diaryltetralin Vepdegestrant Core via an Enantioselective Intramolecular Corey-Chaykovsky Epoxidation

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

An asymmetric synthesis of cis-1,2-diaryltetralin (2), a key chiral intermediate in the Vepdegestrant (1), an orally available PROTAC being evaluated for treatment ER+/HER2- breast cancer, is reported. Chirality initially introduced via catalytic enantioselective intramolecular Corey-Chaykovsky epoxidation utilizing isothiocineole, sulfide. Although several intermolecular epoxidations using sulfides have been reported, our approach represents unique variant. The subsequent introduction cis-1,2-diaryl motif achieved diastereoselective hydrogenation.

Language: Английский

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