Electrophilic C3−H Alkenylation of 2,6‐Dialkoxypyridine Derivatives via Pd(II)/Tl(III) Reaction System DOI Open Access
Takahiro Yamada, Kosaku Tanaka, Yoshimitsu Hashimoto

et al.

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(18), P. 3138 - 3148

Published: July 28, 2023

Abstract Herein, we report the reaction system based on Pd(II) catalyst and Tl(OCOCF 3 ) for electrophilic C3−H alkenylation of 2,6‐dialkokypyridines with alkenes. Synergistic action Pd/thioether ligand catalytic Tl(III) results in efficient C−H various nitrogen heteroaromatics complete regioselectivity. Remarkably, use a sterically hindered thioether Pd(II)/Tl(III) enables mono‐selective C3(5)−H 2,6‐dialkoxypyridines, subsequent introduction second, different alkene affords unsymmetrical, multi‐substituted pyridine derivatives. Mechanistic studies indicate that proceeds via thallation heteroarenes followed by Pd‐catalyzed Heck‐type reaction. The utility this method is showcased its application to late‐stage functionalization structurally complex bioactive molecules having 2,6‐dialkoxypyridine as core structure.

Language: Английский

Skeletal editing of pyridines through atom-pair swap from CN to CC DOI Creative Commons
Qiang Cheng,

Debkanta Bhattacharya,

Malte Haring

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(5), P. 741 - 748

Published: Jan. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Language: Английский

Citations

60
meta‐Selective C−H Functionalization of Pyridines DOI
Hui Cao, Qiang Cheng, Armido Studer

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(42)

Published: April 4, 2023

The pyridine moiety is an important core structure for a variety of drugs, agrochemicals, catalysts, and functional materials. Direct functionalization C-H bonds in pyridines straightforward approach to access valuable substituted pyridines. Compared the direct ortho- para-functionalization, meta-selective far more challenging due inherent electronic properties entity. This review summarizes currently available methods meta-C-H using directing group, non-directed metalation, temporary dearomatization strategies. Recent advances ligand control are highlighted. We analyze advantages as well limitations current techniques hope inspire further developments this area.

Language: Английский

Citations

46
Asymmetric C3-Allylation of Pyridines DOI
Zhong Liu,

Zhu-Jun Shi,

Lu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: unknown

Published: May 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.

Language: Английский

Citations

42
C–H functionalization of pyridines DOI

Susmita Maity,

Asish Bera,

Ayantika Bhattacharjya

et al.

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(28), P. 5671 - 5690

Published: Jan. 1, 2023

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

Language: Английский

Citations

32
Enantioselective C3‐Allylation of Pyridines via Tandem Borane and Palladium Catalysis DOI

Jun‐Jie Tian,

Rui‐Rui Li,

Gui‐Xiu Tian

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: July 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.

Language: Английский

Citations

28
Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch DOI Creative Commons
Pengwei Xu, Zhe Wang, Shu‐Min Guo

et al.

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

13
Palladium-Catalyzed Denitrative Synthesis of Aryl Nitriles from Nitroarenes and Organocyanides DOI

Keiichiro Iizumi,

Hiroki Tanaka, Kei Muto

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(18), P. 3977 - 3981

Published: April 29, 2024

A denitrative cyanation of nitroarenes using organocyanides and a palladium catalyst was developed. The key for this reaction the utilization an aminoacetonitrile as cyano source to avoid generation stoichiometric metal- halogen-containing chemical waste. wide range nitroarenes, including heteroarenes pharmaceutical molecules, can be converted into aryl nitriles.

Language: Английский

Citations

9
Electrochemical meta-C–H sulfonylation of pyridines with nucleophilic sulfinates DOI Creative Commons

Qin Shi,

Mingkai Yang,

Mingyao Xu

et al.

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
Directing Group‐Free Regioselective meta‐C−H Functionalization of Pyridines DOI
Sukriyo Chakraborty, Akkattu T. Biju

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(18)

Published: Feb. 25, 2023

The pyridine core is among the most common motifs found in pharmaceuticals and agrochemicals. Consequently, C-H functionalization of a prized reaction, as it can help access broad spectrum valuable chemicals. However, intrinsic electronic properties pyridines hinder their meta-C-H functionalization, requiring drastic conditions affecting functional group compatibility. A synthetic manoeuvre to overcome this challenge involves temporary conversion into electron-rich intermediates subsequent regioselective electrophilic functionalization. This was recently accomplished by ring-opening ring-closing sequence via Zincke imine McNally co-workers, dearomatization-rearomatization oxazino-pyridine Studer group. mildness simplicity these protocols enable them work with complex molecular setups for synthesizing natural products bioactive molecules.

Language: Английский

Citations

14
Unified ionic and radical C-4 alkylation and arylation of pyridines DOI Creative Commons

Qiu Shi,

Xiaofeng Huang, Ruizhi Yang

et al.

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