A highly divergent Pictet-Spengler approach for pyrrolo[1,2-a]quinoxalines from aryl amine using 1,2-dinitrobenzene as an oxidant

A convenient Pictet-Splengler approach for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from aryl amine and 1-(2-aminoaryl)-pyrrole has been developed. This is the first domino protocol involving formation of benzaldehyde as an intermediate from benzyl amines and benzyl alcohols using 1,2-DNB as an oxidant, followed by its endo cyclization with 1-(2-aminophenyl)-pyrrole to furnish the pyrrolo[1,2-a]quinoxalines. Notably, this procedure exhibits good functional group tolerance as well as good to moderate yield of pyrrolo[1,2-a]quinoxaline.     

Pd-catalyzed oxidative cross-coupling of imidazo[1,2-a]pyridine with arenes

A facile method for direct Pd(OAc)₂-catalyzed oxidative cross-coupling of unactivated imidazo[1,2-a]pyridine with simple arenes has been developed. The reaction shows good reaction efficiency, high regioselectivity, and good functional-group compatibility. This approach provides a useful protocol for the preparation of imidazo[1,2-a]pyridine–arene structure of interest in biological and pharmaceutical materials.     

Indium(III)chloride catalyzed synthesis of novel 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and 1H-pyrazolo[1,2-a]pyridazine-5,8-diones under solvent-free condition

An efficient, inexpensive and environmentally friendly synthesis of novel 3-amino-2-benzoyl-1-aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione and 3-amino-2-benzoyl-1-aryl-1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives has been developed via one-pot three-component reaction of phthalhydrazide or maleic hydrazide, aldehydes and arylacetonitrile in the presence of catalytic amount of InCl₃ as a Lewis acid catalyst under solvent-free conditions. The most important features of the present protocol are mild reaction conditions, short reaction times, high yields, and a wide range of functional group tolerance.     

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.     

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.     

A cyclative cleavage approach to solid-phase synthesis of annulated pyrimidinones using Baylis-Hillman derivatives

An efficient and robust solid-phase synthesis of 6-substituted-2,5,6,8-tetrahydro-3H-imidazo[1,2-a]pyrimidin-7-ones, 3-substituted-1,3,4,6,7,8-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones and 3-substituted-3,4,6,7,8,9-hexahydro-1H-pyrimido[1,2-a][1,3] diazepin-2-ones from the acetates of Baylis-Hillman adducts employing Michael addition of diamines followed by intramolecular cyclization with cyanogen bromide and, finally, base promoted cyclative cleavage has been developed. The procedure is validated through an automated parallel synthesis of a small library of fourteen compounds of the 3H-imidazo[1,2-a]pyrimidin-7-one series.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Highly efficient synthesis of triazolo[1,2-a]indazole-triones and novel spiro triazolo[1,2-a]indazole-tetraones under solvent-free conditions

A new, convenient, and high yielding procedure for the synthesis of triazolo[1,2-a]indazole-triones by the condensation reaction between dimedone, aryl aldehydes, and ueazoles in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO₃H) as a highly stable and reusable eco-friendly degradable polymeric catalyst is described under solvent-free conditions. This procedure has also been applied successfully for the synthesis of novel spiro triazolo[1,2-a]indazole-tetraones.     

A novel one-pot isocyanide-based four-component reaction: synthesis of highly functionalized 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates

A new protocol has been developed for the efficient synthesis of structurally diverse 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates via a four-component reaction of hydrazine hydrate, dialkyl acetylenedicarboxylates, isocyanides and various cyclic anhydrides such as succinic anhydride, maleic anhydride and phthalic anhydride in ethanol/acetone (1:1) at room temperature in good to moderate yields.     

Metal-free,base catalyzed oxidative amination and denitration reaction: Regioselective synthesis of 3-arylimidazo[1,2-a]pyridines

A metal-free, regioselective strategy for the synthesis of 3-arylimidazo[1,2-a]pyridines from β-nitrostyrenes and 2-aminopyridines using triethylamine as the catalyst and H₂O₂ (30% aq.) as the oxidant is reported. The use of an inexpensive base and facile reaction conditions make this strategy a practical alternative for the synthesis of 3-arylimidazo[1,2-a]pyridines.     

Greater variety in Groebke-Blackburn type 3-arylaminoimidazo[1,2-a]azines accessed via Pd-catalyzed arylation of a primary amine precursor

The scope of the Groebke-Blackburn reaction of 2-aminoazines is limited by the availability of isocyanides. To prepare the Groebke-Blackburn type 2-phenyl-3-(hetero)arylaminoimidazo[1,2-a]azines, for which the respective (hetero)arylisocyanides are scarce or unavailable, a general Pd-catalyzed protocol has been developed that is useful for the arylation of known 2-phenylimidazo[1,2-a]pyridin-3-amine and 2-phenylimidazo[1,2-a]pyrazin-3-amine with various electron-deficient aryl and heteroaryl halides.     

Diverse synthesis of pyrimido[1,2-a]benzimidazoles and imidazo[2,1-b]benzothiazoles via CuI-catalyzed decarboxylic multicomponent reactions of heterocyclic azoles,aldehydes and alkynecarboxylic acids

We have developed a straightforward approach to diverse synthesis of 2,3-, 2,4-disubstituted pyrimido [1,2-a]benzimidazoles, 2,4,10-trisubstituted 2,10-dihydropyrimido [1,2-a]benzimidazoles and 2,3-disubstituted imidazo [2,1-b]benzothiazoles via multicomponent reactions (MCRs) of heterocyclic azoles, aldehydes with easily storable and handling alkynecarboxylic acids. In the presence of a catalytic amount of CuI and K₂CO₃, the pyrimido [1,2-a]benzimidazole or imidazo [2,1-b]benzothiazole scaffold could be rapidly constructed through a 6-endo-dig or 5-exo-dig cyclization, respectively. The preliminary mechanistic study suggested that the formation of 2,3- disubstituted pyrimido [1,2-a]benzimidazoles, which completes the assembly of the scaffold and its C-3 position functionalization in one pot, undergoes a novel cascade process involving a decarboxylation, A [3] coupling, 6-endo-dig cyclization, nucleophilic addition and dehydration.     

Synthesis of seven- and eight-membered [1,2-a] alicyclic ring-fused benzimidazoles and 3-aziridinylazepino[1,2-a]benzimidazolequinone as a potential antitumour agent

Azepino and azocino[1,2-a]benzimidazoles were obtained either by treatment of 1-nitrophenyl-2-azacycloalkanes via a one-pot catalytic hydrogenation/acetylation or by treatment of the acetamides generated in the latter reaction with performic acid. This represents the first facile synthesis of eight-membered [1,2-a] alicyclic ring-fused benzimidazoles. 3-Methoxy-azepino[1,2-a]benzimidazole was elaborated to the novel potential cytotoxin, 3-(N-aziridinyl)-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole-1,4-dione. The synthesis included clarification of the reactivity of methoxy-substituted benzimidazoles towards nitration.     

One-pot palladium-catalyzed synthesis of functionalized 10H-pyrido[1,2-a]quinoxalin-10-ones under copper-free conditions

Reactions of 3-substituted-2-chloroquinoxalines, terminal alkynes, and 1,3-dicarbonyl compounds in the presence of palladium catalyst afforded a number of 6,8,9-trisubstituted-10H-pyrido[1,2-a]quinoxalin-10-ones in 60–86% reaction yields. This one-pot protocol provided an efficient, practical, and direct method for the synthesis of pyrido[1,2-a]quinoxalines from readily available starting materials in the absence of a copper salt.     

A general and efficient synthesis of substituted fluorenes and heterocycle-fused indenes containing thiophene or indole rings utilizing a Suzuki-Miyaura coupling and acid-catalyzed Friedel-Crafts reactions as key steps

A general and efficient synthesis of fluorenes or heterocycle-fused indenes including 3-thia-cyclopenta[a]indenes, 9-thia-indeno[1,2-a]indenes, 5,6-dihydroindeno[2,1-b]indoles has been developed. This methodology is realized by a multistep protocol involving first preparation of ortho-formylbiaryls through Suzuki-Miyaura coupling of o-bromobenzaldehydes with arylboronic acids or the coupling of aryl halides with 2-formylbenzene boronic acid, this is followed by Grignard addition and Friedel-Crafts cyclization reactions catalyzed by Brønsted or Lewis acid to form the desired fluorene or indene rings. The method offers several advantages such as high yields, high selectivities, mild reaction conditions, easily accessible starting materials, and so on.     

Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization

A concise synthesis of some new classes of heterocycles (4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diaza-cyclopenta[a]anthracen-6-carbonitriles and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles) has been developed by the ring transformation of suitably functionalized 2H-pyran-2-one with α-oxoketene cyclic aminals to intermediates (8-aroyl-5-aryl-2,3-dihydro-1H-imidazo[1,2-a]pyridine-7-ylidene)-acetonitriles and (9-aroyl-6-aryl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-8-ylidene)-acetonitriles) followed by their photocyclization either in CHCl₃ or acetonitrile. This reaction was further explored for the synthesis of methyl 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carboxylate, 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carbonitriles, 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a,10-triazabenzo[a]anthracene-7-carbonitriles, 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diazacyclopenta[b]phenanthrene-7-carbonitriles from the similar reactions.     

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.     

The synthesis of 3-pyrazinyl-imidazo[1,2-a]pyridines from a vinyl ether

A new method has been developed for the synthesis of 3-pyrazinyl-imidazo[1,2-a]pyridines. 2-Chloro-6-[(Z)-2-ethoxyethenyl]pyrazine was treated with N-bromosuccinimide in dioxane-water to generate the 2-bromo-2-(6-chloropyrazin-2-yl)-1-ethoxyethanol intermediate. In a subsequent one-pot step, optional treatment with various 2-aminopyridines provided the cyclized 3-pyrazinyl-imidazo[1,2-a]pyridines in 31-76% yields.     

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.     

Hypervalent Iodine(III)-Mediated Counteranion Controlled Intramolecular Annulation of Exocyclic β-Enaminone to Carbazolone and Imidazo[1,2-a]pyridine Synthesis

A highly efficient and flexible protocol for intramolecular annulation of exocyclic β-enaminones has been disclosed for the synthesis of carbazolones and imidazo[1,2-a]pyridines through a counter-anion-controlled free-radical mechanism promoted by hypervalent iodine(III). The cooperative behavior of HTIB and AgSbF₆ plays a crucial role in the intramolecular annulation process through C−C and C−N bond formation to give the desired products. The mechanistic insights suggest that the two competitive reactions involved in the system are guided by the nature of the counteranion, which determines the formation of the final products. A wide variety of carbazolones and imidazo[1,2-a]pyridine molecules have been prepared and isolated in good to excellent yields.