Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 15, 2024

Abstract Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C−H-difluoromethylation of represents a highly efficient economic way to access these azines. However, the meta-difluoromethylation has remained elusive methods for site-switchable regioselective meta- para-difluoromethylation are unknown. Here, we demonstrate meta-C−H-difluoromethylation through radical process by using oxazino pyridine intermediates, which easily accessed from pyridines. selectivity can be readily switched para situ transformation pyridinium salts upon acid treatment. preparation various para-difluoromethylated this approach is presented. mild conditions used also allow late-stage or containing drugs. Sequential double functionalization presented, further underlines value work.

Язык: Английский

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Electrochemical meta-C–H sulfonylation of pyridines with nucleophilic sulfinates

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 28, 2024

Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well materials science, a direct meta-selective C-H functionalization is paramount importance, but such reactions remain limited highly challenging. In general, established methods for meta rely on utilization tailored electrophilic reagents to realize intrinsic polarity match. Herein, we report complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation through redox-neutral dearomatization-rearomatization strategy by tandem dearomative cycloaddition/hydrogen-evolution electrooxidative sulfonation resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, facile late-stage modification, have been demonstrated, which further contributes practicality adaptability this approach.

Язык: Английский

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meta-Nitration of Pyridines and Quinolines through Oxazino Azines

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7485 - 7495

Опубликована: Фев. 24, 2025

meta-Nitration of azines (pyridines and quinolines) serves as a powerful method for the prompt construction derivatization several pharmaceuticals, agrochemicals, materials. However, due to inherent electronic properties pyridines, achieving direct selective meta-C-H nitration under mild conditions has been long-standing challenge in synthetic chemistry. Currently, there is no adequate strategy late-stage pyridine-containing drugs drug precursors. To address this void, we introduce practical protocol highly regioselective meta-nitration pyridines using dearomatization-rearomatization strategy. The introduced provides diversification platform at meta-position via radical pathway. This mild, open-air, one-pot, scalable, catalyst-free process employed pyridine containing drugs, precursors, ligands limiting reagents. Consecutive C3 C5 difunctionalization also achieved with complete regiocontrol relying on sequential addition, which further highlights potential presented work. Additionally, obtained products could be transformed into meta-amino azine other valuable building blocks. Incorporating N-heterocyclic amine structures through amidation ibuprofen significantly improved drug's clinical success, highlighting importance

Язык: Английский

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Unified ionic and radical C-4 alkylation and arylation of pyridines

Chemical Science, Год журнала: 2024, Номер 15(31), С. 12442 - 12450

Опубликована: Янв. 1, 2024

A practical and general C-4 functionalization strategy of unbiased pyridines is developed by identifying a readily synthesized substituted urea as the pyridine activation reagent.

Язык: Английский

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Meta‐Selective Copper‐Catalyzed C−H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(26)

Опубликована: Апрель 18, 2024

C(sp

Язык: Английский

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C3 Selective Hydroxylation of Pyridines via Photochemical Valence Isomerization of Pyridine N-Oxides

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(35), С. 24257 - 24264

Опубликована: Авг. 22, 2024

The C–H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains great challenge due to inherent electronic properties this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal selective pyridines via photochemical valence isomerization N-oxides. This metal-free features operational simplicity compatibility with diverse array functional groups, resulting hydroxylated products are amenable further elaboration synthetically useful building blocks. synthetic utility strategy demonstrated effective late-stage functionalization pyridine-containing medicinally relevant molecules versatile derivatizations 3-pyridinols.

Язык: Английский

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Metal-free assembly of diverse polysubstituted pyridines via an efficient cascade approach using tertiary enaminones and α,β-unsaturated sulfonylketimines

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(9), С. 2607 - 2612

Опубликована: Янв. 1, 2024

A metal-free, scalable, and cascade protocol for assembling diverse polysubstituted pyridines from tertiary enaminones α,β-unsaturated sulfonylketimines by cleaving C–N/N–S bonds is reported.

Язык: Английский

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1,3-Difunctionalization of [1.1.1]propellane through iron-hydride catalyzed hydropyridylation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 16, 2024

Current methodologies for the functionalization of [1.1.1]propellane primarily focus on achieving 1, 3-difunctionalized bicyclo[1.1.1]pentane or ring-opened cyclobutane moiety. Herein, we report an innovative approach 3-difunctionalization [1.1.1]propellane, enabling access to a diverse range highly functionalized cyclobutanes via nucleophilic attack followed by ring opening and iron-hydride hydrogen atom transfer. To enable this method, developed efficient iron-catalyzed hydropyridylation various alkenes C - H alkylation pyridines at C4 position, eliminating need stoichiometric quantities oxidants reductants. Mechanistic investigations reveal that resulting N-centered radical serves as effective oxidizing agent, facilitating single-electron transfer oxidation reduced iron catalyst. This process efficiently sustains catalytic cycle, offering significant advantages substrates with oxidatively sensitive functionalities are generally incompatible alternative approaches. The strategy presented herein is not only mechanistically compelling but also demonstrates broad versatility, highlighting its potential late-stage functionalization.

Язык: Английский

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Trinuclear Borane (B₃H₇)-Mediated Selective C4–H Alkylation and Phosphonation of Quinolines and Tetrahydroquinolines

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Herein, we report a method for the regioselective alkylation and phosphonation of quinoline C4–H via B3H7-mediated nucleophilic addition Turbo Grignard reagents phosphine oxide anions to quinolines bearing different substituents, affording 4-alkyl 4-phosphoryl tetrahydroquinolines after one-pot oxidation or reduction. The results indicate that coordination B3H7 group can activate substrates toward potential 1,4-dearomative subtly control regioselectivity by preventing 1,2-dearomative addition.

Язык: Английский

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Unlocking redox-active reactivity of dearomatized pyridines with photochemistry toward meta-C–H functionalization of pyridines

Chem Catalysis, Год журнала: 2025, Номер unknown, С. 101326 - 101326

Опубликована: Март 1, 2025

Язык: Английский

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