A facile synthesis of chromeno[3,4-c]spiropyrrolidine-oxindoles via 1,3-dipolar cycloadditions

A facile one-pot synthesis of chromene bearing novel spiropyrrolidine-oxindoles has been accomplished by the [3+‏2]-cycloaddition reaction of 3-acetyl-2H-chromen-2-ones with azomethine ylides derived in situ from isatin or N-methyl isatin with sarcosine.     

The first iodine improved 1,3-dipolar cycloaddition: facile and novel synthesis of 2-substituted benzo[f]isoindole-4,9-diones

The first novel protocol of the synthesis of 2-substituted benzo[f]isoindole-4,9-dione framework via the one-pot, 1,3-dipolar cycloaddition of quinones, paraformaldehyde and N-substituted amino ester hydrochlorides in the present of iodine at refluxing acetonitrile was reported. All these reactions proceed with good to excellent yields. The promising results obtained 1,3-dipolar cycloaddition will have the potential application in natural product exhibiting important biological activities.     

Synthesis of N-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

The synthesis of 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-dione hydrochlorides is reported starting from 1,4-dihydrobenz[g]isoquinoline-3(2H)-ones or ethyl (3-aminomethyl-1,4-dimethoxynaphth-2-yl)acetates. A third strategy relies on the synthesis of the title compounds via an N-protected 2-(3-bromomethyl-1,4-dimethoxynaphth-2-yl)ethylamine. The synthesized 1,2,3,4-tetrahydro-benz[g]isoquinoline-5,10-diones are a new class of quinones, which have not been reported yet.     

1,3-Dipolar cycloaddition reactions of benzo[b]thiophene 1,1-dioxide with azomethine ylides

New pyrrolo derivatives of benzo[b]thiophene 1,1-dioxide have been synthesised via 1,3-dipolar cycloaddition reactions. Reaction of benzo[b]thiophene 1,1-dioxide with stabilised azomethine ylides gave products in low yield but high stereoselectivity whereas reaction with non-stabilised azomethine ylides gave high overall yields but low stereoselectivity.     

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.     

Synthesis of novel pyrano[2,3-b]quinolines from simple acetanilides via intramolecular 1,3-dipolar cycloaddition

Some novel isoxazole and pyrazole fused pyrano[2,3-b]quinolines were synthesized from simple acetanilides via intramolecular 1,3-dipolar cycloaddition reactions involving nitrones, nitrile oxides and nitrile imines as 1,3-dipoles, in a regioselective manner.     

1,3-Dipolar cycloaddition of 2- and 3-nitroindoles with azomethine ylides. A new approach to pyrrolo[3,4-b]indoles

The 1,3-dipolar cycloaddition of unstabilized azomethine ylides with 2- and 3-nitroindoles furnishes the expected hexahydropyrrolo[3,4-b]indole cycloadducts in good to excellent yields. The cycloadducts can be denitrated with Bu₃SnH/AIBN, and cycloadduct 5 was oxidized with MnO₂ to yield the known pyrrolo[3,4-b]indole 13.     

Synthesis of 5-aminoisoxazolines from N-allyl compounds and nitrile oxides via tandem isomerization-1,3-dipolar cycloaddition

A new strategy for the synthesis of derivatives of 5-aminoisoxazolines via tandem catalytic isomerization (of N-allyl systems to N-(1-propenyl) systems)—1,3-dipolar cycloaddition (of a stable nitrile oxide to N-(1-propenyl) systems) is presented. Rhodium and ruthenium complexes, Verkade’s superbase, and 18-crown-6/KOH system were used for the syntheses of the N-(1-propenyl) systems. 4-P-substituted isoxazoline was also synthesized via cycloaddition of diphenyl(1-propenyl)phosphine (prepared via isomerization of allyldiphenylphosphine) to 2,6-dichlorobenzonitrile oxide. All cycloadditions were regioselective but not stereoselective and not concerted. Cycloaddition to all N-(1-propenyl) systems yielded 5-N-substituted isoxazolines, but cycloaddition to P-(1-propenyl) system lead to the formation of a 4-P-regioisomer. This difference in regioselectivity is predicted by opposite FMO reactivity indices calculated for model compounds: N-(1-propenyl)amine and N-(1-propenyl)phosphine.     

Synthesis of carbamoylpyridine and imidazo[1,5-a]pyridin-1,3-diones via ortho-acetalhydantoin intermediates

A new method for preparing carbamoylpyridine and imidazo[1,5-a]pyridin-1,3-dione rings from an ortho-acetalmethylideneimidazolidin-2,4-dione is described.     

A one-pot synthesis and 1,3-dipolar cycloaddition of [1,2]dithiolo[4,3-b]indole-3(4H)-thiones

Treatment of N-substituted 2-methyl-1H-indoles 1 with S₂Cl₂ and DABCO in chloroform gave the corresponding [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5 by the addition of triethylamine in high yield. 1,2-Dithiole-3-thiones 5 underwent cycloaddition with one or two DMAD equivalents to afford either 2-(3-thioxo-1,3-dihydro-2H-indol-2-ylidene)-1,3-dithioles 10 or fused 4,5-dihydrothiopyrano[3,2-b]indoles 9.     

Efficient construction of highly functionalized endo′-selective spiro[pyrrolidin-2,3′-oxindoles] via a regioselective 1,3-dipolar cycloaddition reaction between 3-amino oxindoles as azomethine ylide precursors and nitroalkenes

An efficient synthesis of novel endo′-selective spiro[pyrrolidin-2,3′-oxindoles] has been achieved via a three component regioselective 1,3-dipolar cycloaddition reaction. The azomethine ylides generated in situ from 3-amino oxindoles and aldehydes reacted with the nitroalkenes to furnish novel pyrrolidine–spirooxindole derivatives bearing one spiro quaternary center and multiple chiral centers in moderate to high yields (up to 99%) with high diastereoselectivities (up to 99:1). The structure and relative stereochemistry of cycloadducts were confirmed by NMR spectra and single crystal X-ray diffraction. The possible mechanism was proposed and the cycloaddition proceeded via endo′-transition state.     

Base-promoted 1,3-dipolar cycloaddition reaction of nitrile oxides with methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate for the construction of naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-diones

A base mediated 1,3-dipolar cycloaddition reaction of methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate with nitrile oxides in situ generated from N-hydroximoyl chlorides was achieved. With this developed protocol, a range of structurally diverse naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-dione derivatives were smoothly obtained in high yields (up to 95%) with up to >20:1 regioselectivities and >20:1 diastereoselectivities under mild conditions. The promising applicability of the protocol was also demonstrated by the further transformations.     

Synthesis of the end-capped 5-(N,N-dimethylamino)naphthyl-1-ethynyl derivatives and their 1,4-di[5-(N,N-dimethylamino)naphthyl]-1,3-butadiynes: anti rotamer structure

A new family of the end-capped 5-(N,N-dimethylamino)naphthylethynyl chains were synthesized, as terminal acetylenes or poly(yne) structures, by heterocoupling between 5-iodo-N,N-dimethylnaphthalen-1-amine and 2-methyl-3-butyn-2-ol or 4-(5-iodo-1-naphthyl)-2-methyl-3-butyn-2-ol, catalyzed by the palladium-copper system. Catalytic homocoupling of the terminal acetylenes, affords to 1,4-dinaphthyl-1,3-butadiyne nanostructures. X-ray diffraction analysis of 1,4-di(α-naphthyl)-1,3-butadiyne shows that the naphthalene rings are in the anti configuration along the acetylene axis. All the conjugated compounds show an important fluorescent emission radiation.     

Highly diastereoselective 1,3-dipolar cycloaddition of nonstabilized azomethine ylides to 3-nitro-2-trihalomethyl-2H-chromenes: synthesis of 1-benzopyrano[3,4-c]pyrrolidines

Reactions of 3-nitro-2-trifluoro(trichloro)methyl-2H-chromenes, including 2-unsubstituted derivatives, with N-alkyl-α-amino acids (sarcosine, proline) and paraformaldehyde proceed diastereoselectively to give 1-benzopyrano[3,4-c]pyrrolidines in good yields as a result of a 1,3-dipolar cycloaddition of the intermediate nonstabilized azomethine ylide at the Δ³-bond of the chromene system.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.     

Synthesis and combinatorial approach of the reactivity of 6- and 7-arylthieno[3,2-d][1,3]oxazine-2,4-diones

This paper describes a general procedure for the synthesis of new substituted thiaisatoic anhydrides or 6- or 7-aryl-1H-thiéno[3,2-d][1,3]oxazine-2,4-diones 3a-j and 4a-f. They were synthesized in large scale under microwave heating conditions with high yields. The reactivity vs nucleophilic reagents of these compounds was studied and permitted to develop a simple combinatorial procedure to synthesize a library of new thiophene ureidoacids 7a-j and 8a-j.     

Synthesis and characterization of 1,3-diarylbenzo[c]selenophenes

A series of 1,3-diarylbenzo[c]selenophenes (symmetrical/unsymmetrical) have been synthesized involving a selenium transfer reaction of keto-alcohol/benzo[c]furan using Woollins reagent. The optical and electrochemical studies of these diarylbenzo[c]selenophenes are correlated with their structures.     

Synthesis of chromeno[3,4-b]pyrrol-4(3H)-ones by cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-nitrocoumarin

The base-mediated cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-nitrocoumarin provides a convenient approach to various chromeno[3,4-b]pyrrol-4(3H)-ones.     

Synthesis and reactivity of pyrrolo[3,2-d][1,3]oxazine-2,4-dione. Access to new pyrrolo[3,2-e][1,4]diazepine-2,5-diones

A convenient synthesis of pyrrolo[3,2-d][1,3]oxazine-2,4-dione 4 is described and its reactivity towards various nucleophiles studied. The regioselective ring opening of anhydride 4 or its N-alkylated analog 25 in the presence of alanine or proline afforded, respectively, imidazolidinedione 22 and N-protected pyrrolo[3,2-e][1,4]diazepines 30 and 31 in a one-pot process. In a last part of this study, an alternative route to produce a library of eight non protected pyrrolo[3,2-e][1,4]diazepine-2,5-diones 35a–h is described to overcome the limited reactivity of anhydride 4.     

Synthesis of monofluorinated indolizines and their derivatives by the 1,3-dipolar reaction of N-ylides with fluorinated vinyl tosylates

Monofluorinated indolizines 4, benzo[d]indolizines 7 and 4H-pyrrolo[1,2-a]benzimidazoles 8 were synthesized in moderate yields by 1,3-dipolar reaction between fluorinated vinyl tosylates 2a and N-ylides of pyridinium, isoquinolinium and benzimidazolinium, generated in situ from their halides salts. When the same N-ylides were allowed to react with 2,3,3-trifluoro-1-propenyl tosylate 2b, the unexpected product formylated indolizines and their derivatives 9 were obtained. The reaction mechanism is also proposed.