Synthesis of Imidazo[1,2-<i>a</i>]pyridines: Triflic Anhydride-Mediated Annulation of 2<i>H</i>-Azirines with 2-Chloropyridines

Vuillermet, Frédéric; Bourret, Joanick; Pelletier, Guillaume

doi:10.1021/acs.joc.0c02148

Cited by 35 publications

(22 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reaction of 2H-azirine 154 with a slight excess of Tf2O in chloroform leads to the formation of the N-acetophenone derivative of triflamide 157 [151] (Scheme 43): The more stable nitrogen-centered radical present on triflamide acts as an intermolecular hydrogen-atom abstractor to the deprotonated triflamides in the solution, which possess highly activated α-CH bonds due to their anionic character. This pivot in reactivity allows for the selective functionalization of both αand δ-CH bonds depending on the installed nitrogen protecting group.…”

Section: Triflamide Derivatives In Organic Synthesismentioning

confidence: 99%

“…The reaction of 2H-azirine 154 with a slight excess of Tf2O in chloroform leads to the formation of the N-acetophenone derivative of triflamide 157 [151] (Scheme 43): 2H-Azirine 154 is activated by a nucleophilic attack by the lone nitrogen pair on the highly electrophilic Tf2O, resulting in the formation of the triflate of the N-triflylazirinium cation 155. In the presence of water in the reaction medium, the iminium ion is hydrolyzed to N-triflyl α-aminoacetophenone 157 (71%).…”

Section: Triflamide Derivatives In Organic Synthesismentioning

confidence: 99%

“…In the presence of water in the reaction medium, the iminium ion is hydrolyzed to N-triflyl α-aminoacetophenone 157 (71%). In anhydrous medium, when 2chloropyridines are added, this 2H-azirine reacts in the presence of Tf 2 O to give imidazo[1,2a]pyridines [151].…”

Section: Triflamide Derivatives In Organic Synthesismentioning

confidence: 99%

See 2 more Smart Citations

Triflamides and Triflimides: Synthesis and Applications

Moskalik

Astakhova

2022

Molecules

View full text Add to dashboard Cite

Among the variety of sulfonamides, triflamides (CF3SO2NHR, TfNHR) occupy a special position in organic chemistry. Triflamides are widely used as reagents, efficient catalysts or additives in numerous reactions. The reasons for the widespread use of these compounds are their high NH-acidity, lipophilicity, catalytic activity and specific chemical properties. Their strong electron-withdrawing properties and low nucleophilicity, combined with their high NH-acidity, makes it possible to use triflamides in a vast variety of organic reactions. This review is devoted to the synthesis and use of N-trifluoromethanesulfonyl derivatives in organic chemistry, medicine, biochemistry, catalysis and agriculture. Part of the work is a review of areas and examples of the use of bis(trifluoromethanesulfonyl)imide (triflimide, (CF3SO2)2NH, Tf2NH). Being one of the strongest NH-acids, triflimide, and especially its salts, are widely used as catalysts in cycloaddition reactions, Friedel–Crafts reactions, condensation reactions, heterocyclization and many others. Triflamides act as a source of nitrogen in C-amination (sulfonamidation) reactions, the products of which are useful building blocks in organic synthesis, catalysts and ligands in metal complex catalysis, and have found applications in medicine. The addition reactions of triflamide in the presence of oxidizing agents to alkenes and dienes are considered separately.

show abstract

Section: Triflamide Derivatives In Organic Synthesismentioning

confidence: 99%

Section: Triflamide Derivatives In Organic Synthesismentioning

confidence: 99%

See 1 more Smart Citation

Triflamides and Triflimides: Synthesis and Applications

Moskalik

Astakhova

2022

Molecules

View full text Add to dashboard Cite

show abstract

“…A two-step, one-pot sequence for the synthesis of 3-substituted derivatives 36 from 2-chloropyridines and 2 H -azirines ( Scheme 12 ) is reported by Vuillermet et al 21 The proposed mechanism involves the formation of an electrophilic 1-trifloyl-aziridin-2-yl triflate species by the reaction of 2 H -azirines with triflic anhydride and further condensation with 2-chloropyridine to transient pyridinium salts followed by treatment with trimethylamine.…”

Section: Recent Metal-free Protocolsmentioning

confidence: 99%

Recent Progress in Metal-Free Direct Synthesis of Imidazo[1,2-a]pyridines

Kurteva

2021

ACS Omega

View full text Add to dashboard Cite

This Mini-Review highlights the most effective protocols for metal-free direct synthesis of imidazo[1,2- a ]pyridines, crucial target products and key intermediates, developed in the past decade. The emphases is given on the ecological impact of the methods and on the mechanistic aspects as well. The procedures efficiently applied in the preparation of important drugs and promising drug candidates are also underlined.

show abstract

“…Examples of the preparation of imidazo[1,2- a ]pyridines by intermolecular reactions of azirines with pyridine derivatives have also been reported. They include the annulation of 2-aminopyridines with 3-carbonylazirines, generated in situ from vinyl azides (Scheme , reaction 2), Tf 2 O-induced annulation of 2-chloropyridines with 3-arylazirines (reaction 3), and CuI-catalyzed annulation of pyridines with vinyl azides, precursors of 3-arylazirines (reaction 4) . Having an important advantage such as the availability of the starting materials, azirines and pyridines, all of these methods, unfortunately, suffer from poor functional group tolerance.…”

mentioning

confidence: 99%

Synthesis of Imidazo[1,2-a]pyridines via Near UV Light-Induced Cyclization of Azirinylpyridinium Salts

et al. 2022

View full text Add to dashboard Cite

An efficient one-pot synthesis of imidazo[1,2a]pyridines from 2-bromoazirines and pyridines has been developed. The construction of the bicyclic framework of imidazo[1,2-a]pyridines occurs in two steps through the formation of (2H-azirin-2-yl)pyridinium bromides followed by dehydrobrominative UV light-induced cyclization. The method can also be applied for the synthesis of imidazo[2,1-a]isoquinolines. Unstable in solution, (2H-azirin-2-yl)pyridinium/isoquinolinium bromides were quantitatively converted to stable tetrafluoroborates, which can be cyclized to imidazo[1,2-a]pyridines under UV irradiation in the presence of bromide ions.2H-Azirines due to their diverse reactivity are widely used in the synthesis of various nitrogen heterocycles. 1 A number of effective methods have been developed to selectively transform the azirine ring into other N-heterocycles, such as dihydroazetes, pyrroles, and pyridines, as well as various N,N-and N,O-heterocycles, such as isoxazoles, oxazoles, pyrazoles, oxazines, pyrazines, and pyrimidines. Azirines are also convenient starting materials for the synthesis of various (3,5)-, (3,6)-, (5,6)-, and (6,6)-bicyclic systems, in which they are embedded as the N−CC, NC−C, or CC structural fragments. The annulations of cyclic molecules with azirines have been successfully applied to the preparation of both nonaromatic and aromatic fused heterocycles, the latter being represented in the literature by incomparably fewer examples. Among them, the methods for the preparation of indoles 2 and their benzo-fused derivatives, 3 benzofurans, 4 and 5H-pyrazino-[2,3-b]indoles 5 are most thoroughly developed. One of the efficient approaches to the synthesis of indoles is a catalytic isomerization of 2-arylazirines. It can also be applied to the preparation of azaindoles (diazaindenes) of pyrazolo[1,5a]pyridine and 1H-pyrrolo[2,3-c]pyridine series using 2-(pyridin-2-yl)-6 or 2-(pyridin-4-yl)azirines 7 as starting compounds (Scheme 1, reaction 1). A significant disadvantage of this method is the limited availability of the starting pyridylazirines because they have to be synthesized from nontrivial pyridine-containing precursors. Azirines with a cationic pyridinium substituent, azirinylpyridinium salts, are completely unknown. At the same time, these compounds could be of interest as potential precursors of such an important class of azaindoles as imidazo[1,2-a]pyridines. The imidazo[1,2-a]pyridine derivatives display anticancer, 8 antiviral, 9 anticonvulsant, 10 antimycobacterial, 11 and antileishmanial 12 activity. They also have attracted a great deal of attention

show abstract

Synthesis of Imidazo[1,2-a]pyridines: Triflic Anhydride-Mediated Annulation of 2H-Azirines with 2-Chloropyridines

Cited by 35 publications

References 71 publications

Triflamides and Triflimides: Synthesis and Applications

Triflamides and Triflimides: Synthesis and Applications

Recent Progress in Metal-Free Direct Synthesis of Imidazo[1,2-a]pyridines

Synthesis of Imidazo[1,2-a]pyridines via Near UV Light-Induced Cyclization of Azirinylpyridinium Salts

Contact Info

Product

Resources

About