Asymmetric Transfer Hydrogenation of Cyclobutenediones

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(7), С. 4942 - 4957

Опубликована: Фев. 7, 2024

Four-membered carbocycles are fundamental substructures in bioactive molecules and approved drugs serve as irreplaceable building blocks organic synthesis. However, developing efficient protocols furnishing diversified four-membered ring compounds a highly regio-, diastereo-, enantioselective fashion remains challenging but very desirable. Here, we report the unprecedented asymmetric transfer hydrogenation of cyclobutenediones. The reaction can selectively afford three types products high yields with stereoselectivities, functionalized enable series further transformations to form more compounds. Asymmetric synthesis di-, tri-, tetrasubstituted has also been achieved. Systematic mechanistic studies theoretical calculations have revealed origin regioselectivity, key transition state models, sequence double triple processes. work provides new choice for catalytic cyclobutanes related structures demonstrates robustness accurate selectivity control substrates.

Язык: Английский

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Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(29), С. 20357 - 20369

Опубликована: Июнь 13, 2024

Developing a general, highly efficient, and enantioselective catalytic method for the synthesis of chiral alcohols is still formidable challenge. We report in this article asymmetric transfer hydrogenation (ATH) N-methyliminodiacetyl (MIDA) acylboronates as general substrate-independent entry to enantioenriched secondary alcohols. ATH acyl-MIDA-boronates with (het)aryl, alkyl, alkynyl, alkenyl, carbonyl substituents delivers variety α-boryl The latter are used range stereospecific transformations based on boron moiety, enabling carbinols two closely related α-substituents, which cannot be obtained high enantioselectivities using direct methods, such (R)-cloperastine intermediate. Computational studies illustrate that BMIDA group privileged enantioselectivity-directing Noyori–Ikariya compared conventionally aryl alkynyl groups due favorable CH–O attractive electrostatic interaction between η6-arene-CH catalyst σ-bonded oxygen atoms BMIDA. work expands domain conventional shows its huge potential addressing challenges symmetric synthesis.

Язык: Английский

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Regio- and Stereoselective Transfer Hydrogenation of Aryloxy Group-Substituted Unsymmetrical 1,2-Diketones: Synthetic Applications and Mechanistic Studies

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(29), С. 20092 - 20106

Опубликована: Июль 15, 2024

Developing a general method that leads to the formation of different classes chiral bioactive compounds and their stereoisomers is an attractive but challenging research topic in organic synthesis. Furthermore, despite great value asymmetric transfer hydrogenation (ATH) both synthesis pharmaceutical industry, monohydrogenation unsymmetrical 1,2-diketones remains underdeveloped. Here, we report aryloxy group-assisted highly regio-, diastereo-, enantioselective ATH racemic 1,2-diketones. The work produces myriad enantioenriched dihydroxy ketones, further transformations furnish all eight diaryl triols, polyphenol, emblirol, glycerol-type natural products. Mechanistic studies calculations reveal two working modes group switching regioselectivity from more reactive carbonyl less one, potential on solving synthetic issues has been clearly demonstrated.

Язык: Английский

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Catalytic Asymmetric Transfer Hydrogenation of β,γ-Unsaturated α-Diketones

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and widely applied in the industrial production of drug molecules. However, despite great success ATH ketones, efficient, regio- stereoselective on enones remains underdeveloped. Moreover, optically pure acyloins 1,2-diols are both extremely useful building blocks organic synthesis, medicinal chemistry, materials science, but concise asymmetric approaches allowing different types have scarcely discovered. We report this paper first efficient readily accessible β,γ-unsaturated α-diketones. The protocol affords four fashion. synthetic value work showcased by divergent synthesis related natural products. systematic mechanistic studies density functional theory (DFT) calculations illustrated origin reactivity divergence, revealed roles aromatic aliphatic substituents substrates, provided range unique rationales not disclosed ATH-related studies.

Язык: Английский

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Fluorohydrins and where to find them: recent asymmetric syntheses of β-fluoro alcohols and their derivatives

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The present work provides an overview of synthetic approaches to fluorohydrins and their fluorinated group derivatives that have been explored in the past decade, as well selected examples these syntheses applied medicinal chemistry.

Язык: Английский

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Consecutive Asymmetric Transfer Hydrogenation of C2-Acylated Quinolines and Quinoxalines: A Diastereodivergent Synthesis of Enantioenriched Tetrahydroquinolines and Tetrahydroquinoxalines Bearing Endo- and Exocyclic Chirality

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Consecutive asymmetric hydrogenation offers a direct and convenient approach to synthesizing complex C(sp3)-enriched products with multiple chirality. Herein, we report an synthesis of chiral 1,2,3,4-tetrahydroquinolines (THQs) tetrahydroquinoxalines bearing both endo- exocyclic vicinal chirality through the consecutive transfer easily accessible C2-acylated quinolines quinoxalines. The method features mild conditions, easy operation, broad substrate scope (42 examples), excellent control (generally >90% ee 20/1 dr). key success is use water-soluble aminobenzimidazole Ir catalyst. Mechanistic experiments support that reaction involves sequential reduction carbonyl group then quinoline core, each step dominated by Remarkably, diastereodivergent all four stereoisomers THQ has been successfully implemented.

Язык: Английский

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Enantioselective Transfer Hydrogenation of α-Methoxyimino-β-keto Esters

The Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

α-Methoxyimino-β-keto esters are reported to undergo highly enantioselective catalytic transfer hydrogenation using the Noyori-Ikariya complex RuCl(

Язык: Английский

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Reversible Redox Ligand-Centered Reactivity in 2,6-Bisiminopyridine Aluminum Systems

Inorganic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 3, 2024

We report the synthesis of cationic 2,6-bisiminopyridine organoaluminum complexes, [(BIP)AlR

Язык: Английский

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Synthesis and applications of optically pure trans-2-(3,5-dimethylphenoxy)cyclohexan-1-ol as chiral auxiliary for preparation of α-substituted carboxylic acid derivatives

Tetrahedron, Год журнала: 2024, Номер unknown, С. 134326 - 134326

Опубликована: Окт. 1, 2024

Язык: Английский

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Iridium‐Catalyzed Asymmetric Transfer Hydrogenation for Facile Access to Optically Active Dihydrodibenzo‐Fused Azepines

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Abstract The asymmetric transfer hydrogenation of various dibenzo‐fused azepines including 5 H ‐dibenzo[ b , e ][1,4]diazepines, dibenzo[ f ][1,4]thiazepines and 11 ]azepines using chiral iridium diamine catalysts HCO 2 H/NEt 3 as the hydrogen source has been accomplished. A range 10,11‐dihydro‐ 5H 10,11‐dihydrodibenzo[ ][1,4]thiazepine 6,11‐dihydro‐5 have prepared in 82–94% yields with 82–99% ee. Diversely substituted substrates are suitable for this transformation, a number functional groups tolerated. Enantiocontrol is achieved via judicious choice catalyst, additive source. synthetic potential reaction explored through gram‐scale reactions without loss reactivity optical purity further transformations on products.

Язык: Английский

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