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

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 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.

Language: Английский

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N-Oxide-to-Carbon Transmutations of Azaarene N-Oxides

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4280 - 4285

Published: May 13, 2024

Reactions that change the identity of an atom within a ring system are emerging as valuable tools for site-selective editing molecular structures. Herein, we describe expansion underdeveloped transformation directly converts azaarene-derived N-oxides to all-carbon arenes. This transmutation exhibits good functional group tolerance and replaces N-oxide moiety with either unsubstituted, substituted, or isotopically labeled carbon atoms in single laboratory operation.

Language: Английский

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meta-Nitration of Pyridines and Quinolines through Oxazino Azines

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7485 - 7495

Published: Feb. 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

Language: Английский

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Regiodivergent Alkylation of Pyridines: Alkyllithium Clusters Direct Chemical Reactivity

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Regiodivergent C-C bond-forming reactions are a powerful tool for constructing diverse molecular architectures from common precursors. While transition metal catalysis has dominated regioselective transformations, achieving similar precision with transition-metal-free methods remains an unmet challenge, particularly when using identical starting materials. In this work, we report transition-metal-free, regiodivergent direct alkylation of electronically unbiased pyridines 1,1-diborylalkanes as the sole alkylating agent. The key to controlling regioselectivity lies in choice alkyllithium activator 1,1-diborylalkanes: methyllithium directs predominantly C4 position, while sec-butyllithium promotes C2-alkylation. Mechanistic studies reveal that structural dynamics clusters dictate regioselectivity, tetrameric favoring C4-alkylation and dimeric preferring This method demonstrates broad substrate scope, enables late-stage functionalization complex molecules, allows sequential installation two distinct alkyl groups onto pyridine scaffold. Our approach provides versatile site-selective functionalization, offering new possibilities synthesizing alkylated pharmaceutical materials research.

Language: Английский

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Six‐Membered Aromatic Nitrogen Heterocyclic Anti‐Tumor Agents: Synthesis and Applications

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(12)

Published: Nov. 27, 2023

Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity explore investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form highly significant category of agents. Among these, agents with six-membered aromatic nitrogen heterocycles have consistently attracted attention chemists pharmacologists. Accordingly, we present comprehensive summary synthetic strategies clinical implications these compounds in this review. entails an in-depth analysis synthesis pathways for pyridine, quinoline, pyrimidine, quinazoline. Additionally, historical progression, targets, mechanisms action, effectiveness small molecule inhibitors possessing structural features.

Language: Английский

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Regiodivergent Arylation of Pyridines via Zincke Intermediates

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(8)

Published: Nov. 21, 2023

Abstract An arylation protocol for pyridines is described, via the ring‐opened Zincke intermediate. Treatment of with triflic anhydride and a secondary amine produces an azahexatriene species, which undergoes regioselective Pd‐catalyzed at putative C4 position. Recyclization then provides pyridine products. Alternatively, metal‐free diaryliodonium salt selective meta ‐position, affording regiodivergent approach to biaryls from common

Language: Английский

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Minisci‐Type Carbamoylation of Azauracils with Oxamic Acids

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(7)

Published: Jan. 19, 2024

Abstract A Minisci‐type carbamoylation of azauracils was developed to afford 6‐carbamoyl in yields up 94 %. In this transformation, oxamic acids were employed as the carbamoyl radical sources under metal‐free conditions. It features high atom economy, good functional group compatibility and convenient operation.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 18, 2024

C(sp

Language: Английский

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Formal meta-C–H-Fluorination of Pyridines and Isoquinolines through Dearomatized Oxazinopyridine Intermediates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 30758 - 30763

Published: Nov. 1, 2024

Organofluorine compounds, including fluorinated pyridines and isoquinolines, play a crucial role in pharmaceuticals, agrochemicals, materials science. However, step-economic selective C-H-functionalization to access these azaarenes is still underexplored, with

Language: 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, Journal Year: 2024, Volume and Issue: 11(9), P. 2607 - 2612

Published: Jan. 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.

Language: Английский

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