Metal-free synthesis of benzimidazo[2,1-a]ellipticines via tandem inter and intramolecular cyclization

Synthesis of the new benzimidazo[2,1-a]ellipticine derivatives via tandem inter and intramolecular, 5-endo,6-endo cyclization of various 9-ethyl-2-(alkynyl)carbazole-3-carbaldehydes with different 1,2-aryldiamines is reported under metal free condition in good yields.     

Synthesis of dihydrobenzoimidazo[2,1-a]isoquinolines

A one-pot protocol toward several substituted 5,6-dihydrobenzo[4,5]imidazo[2,1-a]isoquinolines 1 starting with 2-allylbenzaldehydes 2 was described. The process was carried out the one-pot condensation/hydroamination reaction of substituted 2-allylbenzaldehydes 2 with 1,2-diaminobenzenes 3 in refluxing toluene in good yields. Skeleton 2 was prepared via one-pot ortho-metalative PhBCl₂-mediated double alkylation of hydroxybenzaldehyde 4 with LDA in moderate yields.     

7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines in the search for new indolizine derivatives

7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines were obtained by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides with olefinic (acrylonitrile) and symmetrical or non-symmetrical acetylenic dipolarophiles (methyl/ethyl propiolate, dimethyl acetylenedicarboxylate). Also, stable 5,6,7,8-tetrahydroisoquinolinium dicyanomethylide was isolated and characterized by X-ray diffraction analysis.     

A one-pot conversion of ortho-alkynyl benzaldehydes into indolo[2,1-a]isoquinolines

The conversion of readily available 2-halobenzaldehydes into indolo[2,1-a]isoquinolines in two operations represents a very direct entry to this class of molecules.     

Unusual synthesis of dihydropyrido[2,1-a]isoindolone derivatives by radical cyclization of enamides of Baylis-Hillman adducts

During the radical cyclization of enamide derivatives 4 we found unusual formation of dihydropyrido[2,1-a]isoindolone derivatives 5. The enamides were synthesized in four steps from the Baylis-Hillman adducts of ortho-bromobenzaldehydes.     

Synthesis of the dibenzopyrrocoline alkaloid skeleton: indolo[2,1-a]isoquinolines and related analogues

The indolo[2,1-a]isoquinoline and pyrrolo[2,1-a]isoquinoline nuclei have been synthesized from N-benzylindole or ethyl 1H-indol-1-ylacetate and N-benzylpyrrole precursors, respectively. Firstly, at C-2 of either the indole or pyrrole nucleus, aromatic rings containing a carbonyl substituent ortho to the newly formed biaryl axis were introduced using the Suzuki-Miyaura coupling reaction. Thereafter, under basic conditions the nucleophile that formed at the acidic methylene protons of the N-benzylindole, ethyl 1H-indol-1-ylacetate or N-benzylpyrrole intermediate reacted with the internal aromatic carbonyl to yield (after the expulsion of water) the title compounds. For example, exposure of ethyl 2-(2-(2-formylphenyl)-1H-indol-1-yl)acetate to potassium tert-butoxide resulted in the formation of ethyl indolo[2,1-a]isoquinoline-6-carboxylate.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

One-pot two-step tandem reactions for selective synthesis of pyrrolo[2,1-a]isoquinolines and dihydro-, tetrahydro-derivatives

A sequential one-pot two-step tandem reaction for selective and efficient synthesis of pyrrolo[2,1-a]isoquinoline and its dihydro- and tetrahydro-derivatives has been developed. The tandem reactions of isoquinoline, α-halogenated methylene compounds, aromatic aldehydes, and cyanoacetamide firstly give tetrahydropyrrolo[2,1-a]isoquinolines as main products. The corresponding pyrrolo[2,1-a]isoquinolines and dihydropyrrolo[2,1-a]isoquinolines can be obtained directly by controlling oxidation with DDQ. The mechanism of this tandem reaction involved the 1,3-dipolar cycloaddition of isoquinolinium ylide as the key step. A unique elimination of the amido group preferring to the cyano group has been observed.     

Synthesis of benzimidazo[2,1-b]benzothiazole derivatives through sequential Cu-catalyzed domino coupling and Pd-catalyzed Suzuki reaction

A variety of benzo[d]benzo[4,5]imidazo[2,1-b]thiazoles were efficiently and conveniently synthesized from the Cu-catalyzed domino coupling of o-dihaloarenes with 2-mercaptobenzimidazoles. The reaction is also applicable to a series of multi-functional substrates, affording the halo-containing products with excellent selectivity. The brominated products can further react with arylboronic acids under Pd catalysis to furnish the aryl-substituted benzimidazo[2,1-b]benzothiazole derivatives.     

Synthesis of bridgedhead azolo[3,2-a]pyrimidines and imidazo[2,1-b]thiazines through ring transformation of 2H-pyran-2-ones

Suitably functionalized 3-carbomethoxy/cyano-2H-pyran-2-ones are excellent synthons for the synthesis of arenes and heteroarenes of therapeutic importance. The compounds 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones have been transformed into bridgedhead azolopyrimidines and imidazothiazines through thermal and base-induced ring transformation reactions with aminoazoles and imidazolidin-2-thiones, respectively.     

Cu(OTf)2-promoted efficient synthetic route towards glycospiro-pyrrolo[2,1-a]isoquinolines

A simple, convenient and efficient protocol for the construction of an array of glycospiro-pyrroloisoquinolines using isoquinolinium ylide and a carbohydrate-derived exocyclic olefin in the presence of Cu(OTf)₂–Et₃N catalytic system is described. Isoquinoline and alkylbromoacetates/2-bromoacetophenones were employed to generate the azomethine ylides in the presence of Et₃N in refluxing toluene and subsequent exposure to the olefin led to the desired isoquinoline derivatives.     

Pd-mediated synthesis of novel pentacyclic benzoazepino[2,1-a]isoindoles from enamides of Baylis-Hillman adducts

Novel pentacyclic benzoazepino[2,1-a]isoindole derivatives were synthesized by palladium-mediated consecutive cyclization from enamides of Baylis-Hillman adducts.     

Diversity-oriented decoration of pyrrolo[1,2-a]pyrazines

Diversity-oriented synthesis of a chemical library based on a pyrrolo[1,2-a]pyrazine core is described by using palladium-catalyzed direct C6 arylation of pyrrolo[1,2-a]pyrazines with various aryl bromides. The starting materials, pyrrolo[1,2-a]pyrazines, were easily synthesized by the base-mediated N-alkylation of pyrrole-2-carboxaldehyde with several 2-bromoacetophenones followed by dehydrative cyclization with incorporation of nitrogen by the action of ammonium acetate. Introduction of other functional groups on this chemical scaffold is also discussed herein.     

Novel route for the synthesis of structurally diverse pyrrolo[2,1-a]isoquinoline in aqueous micellar medium

A high yielding environmentally benign protocol has been developed for the synthesis of pyrrolo[2,1-a]isoquinoline using chromone-3-carboxaldehyde, isoquinoline and phenacyl bromide/bromoacetic acid ester as reagents in aqueous micellar medium. The method is operationally simple and more effective compared to the previous methods in terms of the yield of the products as well as the reaction time.     

Novel one pot synthesis of polysubstituted pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidines

We have described a convenient regioselective one-pot approach to pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidine derivatives from α,β-unsaturated imines generated in situ and amino heterocycles. Reaction is general with respect to all three components, namely (i) nitrile, (ii) aldehyde, and (iii) amino heterocycle reagents. Good yields (52-77%), convenient isolation of the targeted molecules are the distinct characteristics of the developed protocol.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

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.     

Studies of some hydrogenated thiazolo[2,3-a]isoquinoline S-oxides

Several hydrogenated thiazolo[2,3-a]isoquinolinone S-oxides have been prepared and their stereochemistry established on the basis of spectral data analysis combined with X-ray crystallography. A reversible syn/anti isomerization of diastereomeric sulfoxides has been postulated to occur via a 10b proton abstraction.     

Synthesis of 2,3-diaryl-5H-imidazo[2,1-a]isoindol-5-ones via the one-pot reaction of 1,2-diketones, 2-formylbenzoic acids, and ammonium acetate

We describe a new one-pot synthesis of 2,3-diaryl-5H-imidazo[2,1-a]isoindol-5-ones via the reaction of 1,2-diketones, 2-formylbenzoic acids, and ammonium acetate in acetic acid under reflux conditions and in the absence of a catalyst.