One-pot synthesis of imidazo[1,2-a]pyridines from benzyl halides or benzyl tosylates, 2-aminopyridines and isocyanides

A one-pot synthesis of imidazo[1,2-a]pyridines is described. Benzyl halides or benzyl tosylates are oxidized to aldehydes under mild Kornblum conditions which then undergo a three-component reaction with various 2-aminopyridines and isocyanides to afford the imidazo[1,2-a]pyridines in excellent yields.     

One-pot,three-component synthesis of 1-amidomethyl-imidazo[1,2-a]pyridines catalyzed by ytterbium triflate

A straightforward method has been developed for the synthesis of 1-amidomethyl-imidazo[1,2-a]pyridines by Yb(OTf)₃ catalyzed three-component reaction of aldehydes, acetamide, and imidazo[1,2-a]pyridines. A series of substituted 3-substituted imidazo[1,2-a]pyridines were synthesized in moderate to good yield (21–74%) under mild reaction condition and the catalyst was recycled for four cycles.     

Iron(III)-catalyzed three-component domino strategy for the synthesis of imidazo[1,2-a]pyridines

An efficient, one-pot, three-component domino strategy has been demonstrated for the synthesis of imidazo[1,2-a]pyridines using a catalytic amount of Fe(III) chloride in high yields in air. A library of imidazo[1,2-a]pyridines was synthesized by the reaction of easily available aldehydes and 2-aminopyridines in a mixture of nitroalkane and DMF (2:1). This transformation presumably occurs by a sequential aza-Henry reaction/cyclization/denitration. The use of readily available chemicals as starting materials, inexpensive metal catalyst, aerobic reaction conditions, tolerance of a wide range of functional groups, and operational simplicity are the notable advantages of this present protocol.     

Multicomponent synthesis of imidazo[1,2-a]pyridines using catalytic zinc chloride

The novel use of zinc chloride to catalyze the one-pot, three component synthesis of imidazo[1,2-a]pyridines from a range of substrates using either conventional heating or microwave irradiation is described. This methodology affords a number of imidazo[1,2-a]pyridines in reasonable yields and short reaction times without any significant optimization of the reaction conditions.     

Silica-sulfuric acid: a highly efficient catalyst for the synthesis of imidazo[1,2-a]pyridines using trimethysilyl cyanide or cyanohydrins

This Letter describes a novel synthetic approach towards imidazo[1,2-a]pyridines via a three-component condensation using trimethylsilyl cyanide (TMSCN) or cyanohydrins as the source of CN⁻ ions and silica-sulfuric acid as the catalyst.     

Ultraviolet irradiation of terarylenes: A facile,efficient, and environmentally friendly method for the synthesis of fused polycyclic products

Ultraviolet irradiation of hydroxyl substituted terarylenes provided a simple, efficient, and environmentally friendly method for the synthesis of imidazo[1,2-a]pyridines. The starting terarylenes were prepared via the one-pot, three-component condensation of readily accessible arylglyoxals, 2-aminopyridines, and dimedone.     

Efficient synthesis and antioxidant activity of coelenterazine analogues

A convenient and highly convergent method for the synthesis of new imidazo[1,2-a]pyridine-based coelenterazine analogues is reported. The imidazo[1,2-a]pyridine core was constructed through a condensation between 2-aminopyridine analogues and arylglyoxals. Additionally, a new approach to the synthesis of benzylglyoxals was introduced. The imidazo[1,2-a]pyridines display moderate antioxidant activities at a low micromolar level in 2,2-diphenyl-1-picrylhydrazyl (DPPH).     

A novel three-component reaction of N-fluoropyridinium salts: a facile approach to imidazo[1,2-a]pyridines

The reaction of N-fluoropyridinium triflate with isonitriles in acetonitrile and propionitrile in the presence of NaBH(OAc)₃ led to the formation of the corresponding imidazo[1,2-a]pyridines in 44-73% yields. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species and apparent reduction of the pyridinium intermediate with NaBH(OAc)₃ to yield the targeted heterocycles.     

Pd-catalyzed regiocontrolled Sonogashira and Suzuki cross-coupling reaction of 3,6-dihalogenoimidazo[1,2-a]pyridines: one-pot double-coupling approach

New and efficient regioselective Sonogashira and Suzuki-Miyaura palladium-catalyzed coupling reactions of 3,6-dihalogenoimidazo[1,2-a]pyridines followed by another cross-coupling has been successfully developed. Various solvents, palladium species and bases were tested. Scope and limitations of this regiocontrolled palladium-catalyzed reaction were investigated. The synthesis of 3,6-disubstituted imidazo[1,2-a]pyridine derivatives using one-pot regioselective double-coupling approach was developed. This procedure affords convergent syntheses of polysubstituted compounds in high yields in a very few steps.     

NBS mediated protocol for the synthesis of N-bridged fused heterocycles in water

A facile and environmental friendly protocol for the synthesis of N-bridged fused bicyclic compounds such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[2,1-b]thiazole, from commercially available starting materials has been developed. The reaction proceeds via NBS mediated in situ formation of α-brominated intermediate of corresponding aromatic ketones, 1,3-diketones, β-keto esters, followed by trapping with suitable nucleophiles to provide these versatile imidazole fused bicyclic heterocycles in good yields under metal-free conditions.     

Diversity-Oriented Synthesis of [2.2]Paracyclophane-derived Fused Imidazo[1,2-a]heterocycles by Groebke-Blackburn-Bienaymé Reaction: Accessing Cyclophanyl Imidazole Ligands Library

This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.     

Recent synthetic scenario on imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridines chemical intermediate

Of the biologically important benzene fused heterocycles, the most important are those containing a ring-junction nitrogen. The majority of ring junction systems do not occur naturally, but they have been important from a theoretical viewpoint, for preparation of potentially active analogues. The imidazo[1,2-a] pyridines are an important class of nitrogen ring junction heterocyclic compounds. They have huge applications in medicinal chemistry and drug molecule production. Thus, the initial discussion focuses on synthetic strategies of imidazo[1,2-a] pyridines, and later we disclose the reactivity of the imidazo[1,2-a]pyridines. This review is intended to summarize and discuss the most recent developments of synthesis and reactivity of imidazo[1,2-a]pyridines, mainly the contributions after 2007.     

Copper-catalyzed four-component synthesis of imidazo[1,2-a]pyridines via sequential reductive amination,condensation, and cyclization

A novel and efficient four-component approach for the synthesis of 2,3-disubstituted imidazo[1,2-a]pyridines is described. The copper-catalyzed reductive amination of 2-bromopyridine by sodium azide followed by sequential condensation and cyclization with aldehydes and isocyanides afforded the corresponding imidazo[1,2-a]pyridines in good yields.     

A visible-light-promoted cross-dehydrogenative-coupling reaction of N-arylglycine esters with imidazo[1,2-a]pyridines

A mild and convenient visible-light-promoted cross-dehydrogenative-coupling reaction between N-arylglycine esters and imidazo[1,2-a]pyridines for the construction of CC bond was developed. A range of N-arylglycine esters and imidazo[1,2-a]pyridines were able to undergo the CDC reaction readily to afford α-heteroaryl substituted α-amino acid derivatives in good to excellent yields. A tentative mechanism for the photoredox reaction was also proposed. Importantly, the use of copper(II) salt as the sole catalyst in this visible-light-promoted transformation makes this reaction sustainable and practical.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

K2S2O8-Mediated halogenation of 2-arylimidazo[1,2-a]pyridines using sodium halides as the halogen sources

A convenient halogenation of 2-arylimidazo[1,2-a]pyridines using sodium chloride/bromide/iodide as the halogen sources in the presence of K₂S₂O₈ as an easy-to-handle oxidizing agent was developed. The present work offers an efficient and rapid access to 3-chloro-, 3-bromo- and 3-iodo-2-arylimidazo[1,2-a]pyridines which can be readily converted to C3-substituted imidazo[1,2-a]pyridines by cross-coupling reactions.     

Synthesis of 1,3-diarylated imidazo[1,5-a]pyridines with a combinatorial approach: metal-catalyzed cross-coupling reactions of 1-halo-3-arylimidazo[1,5-a]pyridines with arylmetal reagents

The halogenation of 3-arylimidazo[1,5-a]pyridines was carried out with iodine, bromine, N-chlorosuccinimide, and 1-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate as halogenating agents to give selectively halogenated products 1-halo-3-arylimidazo[1,5-a]pyridines in good to excellent yields. Kumada-Tamao-Corriu cross-coupling of the obtained 1-iodo-3-arylimidazo[1,5-a]pyridines and aryl Grignard reagents led to 1,3-diarylated imidazo[1,5-a]pyridines in good to excellent yields. Suzuki-Miyaura cross-coupling of the 1-bromo-3-phenylimidazo[1,5-a]pyridine and p- or m-methoxycarbonylphenylboronic acids furnished the coupling product in respective yields of 91% and 61%. The obtained 1,3-diarylated imidazo[1,5-a]pyridines showed a wide variety of fluorescent emissions in a wavelength range of 449-533 nm with improved quantum yields compared to monoarylated ones.     

One-pot Copper Nanoparticle-catalyzed Synthesis of Imidazo[1,2-α]pyridines Under Solvent-free Conditions

A direct and efficient approach to synthesize imidazo[1,2-α]pyridines through three-component one-pot reaction of 2-aminopyridine,aldehyde and terminal alkyne catalyzed by Cu-nanoparticles under solvent-free conditions has been developed.This method provides a rapid access to substituted imidazo[1,2-α]pyridines with good yields（up to 85％）.     

Oxone®-mediated direct arylselenylation of imidazo[2,1-b]thiazoles,imidazo[1,2-a]pyridines and 1H-pyrazoles

Oxone mediated reaction of imidazo[2,1-b]thiazole, imidazo[1,2-a]pyridine and 1H-pyrazole derivatives with diaryl diselenides is presented here. The methodology represents an efficient and simple protocol for carrying out the selective synthesis of 5-arylselanyl-imidazo[2,1-b]thiazoles, 3-arylselanyl-imidazo[1,2-a]pyridines and 4-arylselanyl-1H-pyrazoles in high yields using a stable, nontoxic and cheap oxidant. The reactions were conducted at 60?°C in air using acetonitrile as solvent. Alternatively, the use of ultrasound irradiation is presented as a tool for fast and efficient energy transfer that significantly reduced the reaction time.