Chemistry of Heterocyclic Compounds, Journal Year: 2024, Volume and Issue: 60(5-6), P. 299 - 303
Published: June 1, 2024
Language: Английский
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
Citations
12
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Aug. 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.
Language: Английский
Citations
9
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
Citations
1
Chemical Science, Journal Year: 2024, Volume and Issue: 15(31), P. 12442 - 12450
Published: Jan. 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.
Language: Английский
Citations
6
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)
Published: April 18, 2024
C(sp
Language: Английский
Citations
5
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(35), P. 24257 - 24264
Published: Aug. 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.
Language: Английский
Citations
5
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
Citations
4
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: July 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.
Language: Английский
Citations
4
Organic Letters, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 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.
Language: Английский
Citations
0
Chem Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 101326 - 101326
Published: March 1, 2025
Language: Английский
Citations
0