Late-Stage C–H Functionalization of Azines

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7655 - 7691

Опубликована: Май 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

Язык: Английский

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Dienes as Versatile Substrates for Transition Metal‐Catalyzed Reactions

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(20)

Опубликована: Март 4, 2024

Abstract Dienes have been of great interest to synthetic chemists as valuable substrates due their abundance and ease synthesis. Their unique stereoelectronic properties enable broad reactivity with a wide range transition metals construct molecular complexity facilitating synthesis biologically active compounds. In addition, structural diene variation can result in substrate‐controlled reactions, providing mechanistic insights into selectivity patterns. The last decade has seen wealth new methodologies involving through the power metal catalysis. This review summarizes recent advances remaining opportunities for metal‐catalyzed transformations dienes.

Язык: Английский

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Asymmetric C3-Allylation of Pyridines

Journal of the American Chemical Society, Год журнала: 2023, Номер unknown

Опубликована: Май 17, 2023

Asymmetric intermolecular C–H functionalization of pyridines at C3 is unprecedented. Herein, we report the first examples such transformations: specifically, C3-allylation via tandem borane and iridium catalysis. First, borane-catalyzed pyridine hydroboration generates nucleophilic dihydropyridines; then, dihydropyridine undergoes enantioselective iridium-catalyzed allylation; finally, oxidative aromatization with air as oxidant gives C3-allylated pyridine. This protocol provides direct access to excellent enantioselectivity (up >99% ee) suitable for late-stage pyridine-containing drugs.

Язык: Английский

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Ni-Catalyzed Enantioselective Hydrofunctionalizations of 1,3-Dienes

ACS Catalysis, Год журнала: 2022, Номер 12(24), С. 15638 - 15647

Опубликована: Дек. 6, 2022

Ni-catalyzed enantioselective hydrofunctionalizations of conjugated dienes are particularly demanding reactions to devise because they require not only addressing the inherent challenges associated with development an transformation but also overcoming all other aspects selective catalysis (chemoselectivity, regioselectivity, diastereoselectivity, etc.). However, value-added nature chiral allylic and homoallylic derivatives obtained by these methods, lack efficient alternatives, use earth-abundant first-row transition metal have led renewed interest over past decade. In this Perspective, we give overview developments in field, from original findings (often dating back last century) most recent contributions. Emphasis is placed on hydrofunctionalization agent (C(sp), C(sp2), C(sp3), N, P, or O).

Язык: Английский

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Enantioselective Hydroalkoxylation of 1,3-Dienes via Ni-Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 3909 - 3914

Опубликована: Фев. 10, 2023

As an advance in hydrofunctionalization, we herein report that alcohols add to 1,3-dienes with high regio- and enantioselectivity. Using Ni-DuPhos, access enantioenriched allylic ethers. Through the choice of solvent-free conditions, control reversibility C–O bond formation. This work showcases a rare example methanol as reagent asymmetric synthesis.

Язык: Английский

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C–H functionalization of pyridines

Organic & Biomolecular Chemistry, Год журнала: 2023, Номер 21(28), С. 5671 - 5690

Опубликована: Янв. 1, 2023

This review discusses known approaches for selective pyridine C–H editing, focusing on recent discoveries uniquely suited to pyridines.

Язык: Английский

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Enantioselective C3‐Allylation of Pyridines via Tandem Borane and Palladium Catalysis

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(34)

Опубликована: Июль 3, 2023

Abstract Herein, we report a one‐pot method for enantioselective C−H allylation of pyridines at C3 via tandem borane and palladium catalysis. This involves borane‐catalyzed pyridine hydroboration to generate dihydropyridines, then palladium‐catalyzed the dihydropyridines with allylic esters, finally air oxidation allylated afford products. enables introduction an group excellent regio‐ enantioselectivities.

Язык: Английский

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Aluminum-Containing Heterobimetallic Complexes as Versatile Platforms for Homogeneous Catalysis

ACS Catalysis, Год журнала: 2023, Номер 13(19), С. 12519 - 12542

Опубликована: Сен. 11, 2023

Within the broader area of heterobimetallic catalysis, Al/M compounds (M = any metal) are promising for design and execution catalytic manifolds. This Perspective reviews recent advances in focusing on their applications. Topics include polymerization, epoxide activation carbonylation, C–H functionalization, other important transformations mediated by catalysts. In each case, mechanistic role aluminum site is highlighted. A broad range Al-containing metalloligands combinations included to construct this comprehensive perspective.

Язык: Английский

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Nickel-Catalyzed Atroposelective C–H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9172 - 9180

Опубликована: Март 21, 2024

The catalytic asymmetric construction of axially chiral C–N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C–H alkylation for compounds with aid heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni–Al bimetallic catalyst. A wide range alkenes, including terminal internal were well compatible reaction, providing variety benzimidazole derivatives in high yields enantioselectivities (up 97:3 e.r.). key success was identification novel HASPOs as highly effective preligands. Mechanistic studies revealed catalyst mode action, in-depth data science analysis elucidated features responsible preligands controlling enantioselectivity.

Язык: Английский

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Dearomative Addition-Hydrogen Autotransfer for Branch-Selective N-Heteroaryl C–H Functionalization via Ruthenium-Catalyzed C–C Couplings of Diene Pronucleophiles

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

Опубликована: Янв. 6, 2025

A novel mechanism for N-heteroaryl C–H functionalization via dearomative addition-hydrogen autotransfer is described. Upon exposure to the catalyst derived from RuHCl(CO)(PPh3)3 and Xantphos, dienes 1a–1g suffer hydroruthenation form allylruthenium nucleophiles that engage in addition-β-hydride elimination furnish branched products of C–C coupling 3a–3s 4a–4f. Oxidative cleavage isoprene adducts 3j, 3k, 3l, 3n followed by ruthenium-catalyzed dynamic kinetic asymmetric ketone reduction provides enantiomerically enriched N-heteroarylethyl alcohols 6a–6d and, therefrom, amines 7a–7d. Density functional theory calculations correlate experimentally observed regioselectivities with magnitude LUMO coefficients corroborate rate-determining addition. In presence 2-propanol trifluoroethanol, dearomatized pyrimidine 2a quinazoline 2n were isolated characterized.

Язык: Английский

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