Synthesis of pyrrolo[3,4-c]quinolines by 1,5-electrocyclisation of non-stabilised azomethine ylides

A new route to the pyrrolo[3,4-c]quinoline ring system has been developed via the 1,5-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formylquinoline derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed dipoles with N-phenylmaleimide.     

Synthesis of pyrrolo[3,4-c]quinolines by 1,5-electrocyclisation of non-stabilised azomethine ylides

A new route to the pyrrolo[3,4-c]quinoline ring system has been developed via the 1,5-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formylquinoline derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed dipoles with N-phenylmaleimide.     

Synthesis of benz[5,6]azepino[4,3-b]indoles by 1,7-electrocyclisation of azomethine ylides

A new, general route to the benz[5,6]azepino[4,3-b]indole ring system has been developed via the 1,7-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formyl indole derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed α,β:γ,δ-conjugated dipole with N-phenylmaleimide.     

Reaction of functionalized azomethine ylides with acetylenic dipolarophiles: the facile synthesis of functionalized 2H- and 1H-pyrroles

The reaction of functionalized azomethine ylides as C-unsubstituted nitrile ylide equivalents with acetylenic dipolarophiles is mentioned. Therein, the initially formed cycloadducts, 2,5-dihydropyrroles, by the reaction of the azomethine ylides with substituted acetylenes, undergo a fission reaction to afford 2H-pyrroles and the parent heterocyclic system. Some 2H-pyrroles isomerized to 1H-pyrroles under both thermal and acidic conditions.     

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.     

The first example of the generation of azomethine ylides from a fluorocarbene: 1,3-cyclization and 1,3-dipolar cycloaddition

The reaction of Schiff bases with fluorocarbene, generated by reduction of dibromofluoromethane with active lead in the presence of Bu₄NBr under ultrasound irradiation, involves the formation of fluoro-substituted azomethine ylides which undergo cyclization into aziridines. 1,3-Cyclization of ylides, generated from N-arylimines of benzaldehyde, proceeds stereoselectively. When carrying out the reaction of Schiff bases with fluorocarbene in the presence of dimethyl maleate or dimethyl acetylenedicarboxylate, the products of dehydrofluorination of the primary adducts of the 1,3-dipolar cycloaddition of fluoro-substituted azomethine ylides to multiple bonds of dipolarophiles were obtained. In the case of the reaction of N-alkylimines of benzaldehyde the cycloaddition of ylides to dimethyl maleate completely suppressed the cyclization to aziridines.     

Thermal transformations of alk-1-enyl-N-phthalimidoaziridines

Thermolysis of alk-1-enyl-N-phthalimidoaziridines leads to products of 1,5-electrocyclization of intermediate azomethine ylides with participation of C=C bonds. If acyl or alkoxycarbonyl substituent is present in the aziridine ring, the C=O bond is also involved. Thermolysis of the title compounds in the presence of N-phenylmaleimide or dimethyl acetylenedicarboxylate under analogous conditions gives products of 1,3-dipolar cycloaddition of azomethine ylides to the double or triple bond of the dipolarophile.     

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes has been developed. In the presence of FeCl₂ (10 mol %) and α,α-bis(3,5-bistrifluoromethylphenyl)prolinol L1 (10 mol %), [3+2] cycloaddition of azomethine ylides with electronic-deficient olefins underwent smoothly in CH₃CN at room temperature to generate the desired endo-adducts in moderate to good yields and enantioselectivities. This is the first example of Fe(II)/N,O-ligand (L1) catalyzed 1,3-dipolar enantioselective cycloaddition reaction of azomethine ylides.     

Cu-Fesulphos complexes: efficient chiral catalysts for asymmetric 1,3-dipolar cycloaddition of azomethine ylides

The Cu^I-Fesulphos catalyst system (≤3 mol %) shows an excellent performance in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. High to very high levels of reactivity, endo/exo selectivity, and enantioselectivity (69->99% ee) are generally achieved with a very wide range of azomethine ylides and dipolarophiles. Based on experimental and computational studies data, a model that accounts for this high enantiocontrol is proposed.     

X=Y=ZH Systems as potential 1,3-dipoles. Part 58: Cycloaddition route to chiral conformationally constrained (R)-pro-(S)-pro peptidomimetics

Imines of (1S,9S)-t-butyl-9-amino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate undergo thermal (toluene, 110°C) or LiBr-DBU catalysed (MeCN, room temperature) regio- and stereo-specific cycloaddition to a range of chiral dipolarophiles giving enantiopure spiro-cycloadducts in excellent yield. The reactions proceed via intermediate NH azomethine ylides and litho azomethine ylides, respectively and results in the multiplication of chiral centres from 2 (one of which is lost in the process) to 5.     

A new, one-step synthesis of 1-heteroaryl-2-alkylaminoethanols

Refluxing a mixture of a heteroarylcarboxaldehyde and an N-alkylamino acid in dry toluene, in the presence of 4 Å molecular sieves, results in the formation of β-hydroxyamines through the 1,3-electrocyclisation of an azomethine ylide and the subsequent ring-opening hydrolysis of an aziridine. The intermediacy of an azomethine ylide in this process is suggested by the isolation of oxazolidines from the cycloaddition of the azomethine ylides to their aldehyde precursors.     

Proline-mediated dimerization of cinnamaldehydes via 1,3-dipolar cycloaddition reaction with azomethine ylides. A rapid access to highly functionalized hexahydro-1H-pyrrolizine

1,3-Dipolar cycloaddition reaction of cinnamaldehyde with azomethine ylides generated through decarboxylation of iminium or oxazolidinone intermediate formed by the reaction of l-proline with cinnamaldehydes is reported. The stereoselective reaction provides an efficient access to the highly functionalized hexahydro-1H-pyrrolizine.     

Catalytic bimetalic [Pd(0)/Ag(I) Heck-1,3-dipolar cycloaddition cascade reactions accessing spiro-oxindoles. Concomitant in situ generation of azomethine ylides and dipolarophile

Spiro-oxindoles, epi-Spirotryprostatin A and its analogues were prepared from a tactical combination of cascade catalytic bimetallic Pd (0)/Ag(I), intramolecular Heck and subsequent imine → azomethine ylide → 1,3-Dipolar cycloaddition reactions. The cascade features in situ generation of azomethine ylides and dipolarophiles and produces two new rings together with three stereocentres in good to excellent yields.     

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.     

Nonstabilized azomethine ylides in the synthesis of aryl cucurbitine derivatives

Nonstabilized azomethine ylides react with 4-arylidene-2-phenyloxazol-5(4H)-ones to form diazaspiro[4.4]nonenes, which were hydrolyzed to aryl cucurbitine derivatives in 35–67% overall yield.     

Cu(I)/DTBM-BIPHEP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with cis-trifluorocrotonate for asymmetric construction of trifluoromethylated pyrrolidines

A direct and facile access to highly substituted exo-pyrrolidines bearing a unique trifluoromethyl group is developed via Cu(I)/DTBM-BIPHEP-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with cis-4,4,4-trifluorocrotonate for the first time.     

1,7-Electrocyclization reactions of stabilized α,β:γ,δ-unsaturated azomethine ylides

Stabilized α,β:γ,δ-unsaturated azomethine ylides were generated by the deprotonation of isoquinolinium salts. 1,7-Electrocyclization of these dipoles, followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines.     

Synthesis of indazole-N-oxides via the 1,7-electrocyclization of azomethine ylides

The first examples of the 1,7-electrocyclization of azomethine ylides onto a nitro group, to give benz-1,2,6-oxadiazepine intermediates are reported. Subsequent ring contraction results in the formation of indazole-N-oxides.     

An expedient approach for the regio- and stereoselective synthesis of novel spiroindolizidines via [3+2] cycloaddition

A new series of spiroindolizidines was synthesized by one-pot, three-component condensation of azomethine ylides, generated from 1,2,3,4-tetrahydroisoquinoline with ninhydrin or isatin derivatives by a 1,5-prototropic shift route, with various derivatives of trans-β-nitrostyrene in a regio- and stereoselective manner. X-ray crystal structure analysis and NMR spectroscopic data confirmed the structure outcome of the cycloaddition reaction.     

A simple two-step synthesis of 2-(alkylamino)-1-arylethanols,including racemic adrenaline,from aromatic aldehydes via 5-aryloxazolidines

Benzaldehydes react smoothly with nonstabilized azomethine ylides, generated in situ from sarcosine/formaldehyde or N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine, to give 5-aryloxazolidines as intermediates. These were converted into 2-(alkylamino)-1-arylethanols in good yields by simple heating in methanol with hydrochloric acid, or by treatment with hydrazine hydrate in ethanol.