New Light-Induced Iminyl Radical Cyclization Reactions of Acyloximes to Isoquinolines

Alonso, Rafael; Campos, Pedro J.; Garcı́a, Bárbara; Rodrı́guez, Miguel A.

doi:10.1021/ol061258i

Cited by 163 publications

(52 citation statements)

References 7 publications

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“…All the spectral data obtained for this compound were in agreement with those reported previously. 15 Thus, the presence of a 2-pyridyl substituent at position 3 of the 1,2,4-triazine is necessary for the transformation of the 1,2,4-triazine into a 1,2,3-triazole (Scheme 3). In summary, a non-trivial method for the synthesis of 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles 3 has been reported.…”

mentioning

confidence: 99%

Benzyne-mediated rearrangement of 3-(2-pyridyl)-1,2,4-triazines into 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles

Nikonov

Kopchuk

Коvalev

et al. 2013

Tetrahedron Letters

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a b s t r a c tThe reaction between 5-R-6-R 1 -3-(2-pyridyl)-1,2,4-triazines and benzyne generated in situ in toluene under reflux results in the formation of 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles 3 in up to 60% yields instead of the expected 3-R-4-R 1 -1-(2-pyridyl)isoquinolines 2. The crystal structure of product 3c and the proposed mechanism for the formation of 3 are reported.Ó 2013 Elsevier Ltd. All rights reserved.Aryne intermediates are of wide use as versatile tools for the synthesis of various heteroaromatic systems, 1 including photoluminescent intercalators 2 and other physiologically active compounds, such as alkaloids and their carbo-and heterocyclic analogs, 3 and fluorescent sensors for nitroaromatics. 4 At present, most of these compounds can be obtained via the one-step Diels-Alder reaction between various heteroaromatic dienes and cyclic (het)arynes as dienophiles. However, little attention has been given to the reactions of arynes as dienophiles and various cyclic azines as extremely active dienes, the so-called inverse electron demand Diels-Alder reactions. 5 In particular, only a few cases of reactions between 1,2,4-triazines and benzyne to afford isoquinolines in low yields have been described. 6 Moreover, only two cases have been reported for the formation of benzene-annelated analogs of highly promising 2,2 0 -bipyridine-type ligands 7 by the one-step inverse electron demand Diels-Alder reaction between 5-phenyl-3-(2-pyridyl)-1,2,4-triazine and in situ generated benzyne under very harsh conditions: autoclave, toluene, 140°C, 8 or by heating in o-dichlorobenzene at 160°C. 9In addition, we have developed an alternative synthetic approach toward aryl-substituted 1-(2-pyridyl)isoquinolines via the Diels-Alder reaction of 3-(2-pyridyl)-1,2,4-triazines with 1-morpholinocyclohexene followed by aromatization of the resultant tetrahydrosoquinolines. 10Herein we report the results of our study on the reactions of het(aryl)-substituted-1,2,4-triazines with benzyne, which was aimed at the development of a convenient method for the onepot conversion of 1,2,4-triazines into isoquinolines, including benzene-annelated 2,2 0 -bipyridyl ligands. Aryl-substituted 3-(2-pyridyl)-1,2,4-triazines 1a-c were synthesized according to published methods 11 and were used as the starting materials (Scheme 1). Surprisingly, in the reactions between 1a-c and benzyne generated in situ from 2-aminobenzoic acid and isoamyl nitrite 12 in toluene under reflux, we did not observe the formation of the expected pyridyl-isoquinolines 2. Analysis of the 1 H NMR spectra of the obtained products and compound 2a, prepared by an alternative method, 10 did not show any matches, that is, the resonances of the aromatic protons in the products were downfield compared to the similar resonances observed for compound 2a. In addition, according to ESI-mass spectrometry there were four nitrogen atoms in molecules of products 3a-c versus two nitrogen atoms in product 2a. The initial suggestion that the reaction of compound 1 and be...

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confidence: 99%

Benzyne-mediated rearrangement of 3-(2-pyridyl)-1,2,4-triazines into 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles

Nikonov

Kopchuk

Коvalev

et al. 2013

Tetrahedron Letters

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“…The light-induced intermolecular attack of the iminyl radical on a carbon-carbon triple bond has also been reported (Alonso et al, 2006). As shown in Scheme 9, irradiation of Similarly, the iminyl radicals generated by the action of UV light are capable of reacting with alkynyl Fischer carbenes (Blanco-Lomas et al, 2011).…”

Section: Cleavage Of N-o Bondsmentioning

confidence: 85%

“…The reaction is also effective for carbon-carbon triple bonds (Alonso et al, 2006). In the intramolecular version, the addition of a nitrogen-centred radical should generate an isoquinolyl radical, which may evolve by atom abstraction since the use of 2-propanol-d 7 as solvent led to 4-deuteroquinoline, while the use of methanol-d 1 led to nondeuterated isoquinoline (Scheme 8).…”

Section: Cleavage Of N-o Bondsmentioning

confidence: 99%

“…This kind of attack by iminyl radicals was previously observed when the photolysis of aromatic ketone O-acyloximes took place in aromatic solvents and this process involves a homolytic aromatic substitution (Sakuragi et al, 1976). Starting from appropriately substituted oximes (Scheme 11), different phenanthridines were obtained in good to excellent yields after intramolecular cyclization onto a phenyl ring followed by rearomatisation (Alonso et al, 2006). In the case of aldehyde O-acyloxime (R = H) the iminyl radical partially decomposed into a nitrile (Bird et al, 1976).…”

Section: Cleavage Of N-o Bondsmentioning

confidence: 99%

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Light-Induced Iminyl Radicals: Generation and Synthetic Applications

Barranco¹

2012

Molecular Photochemistry - Various Aspects

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“…Photocyclisation of the O-acetyloximes 34 of 2-phenylbenzaldehyde, 2-phenylacetophenone and 2-phenylbenzophenone to the corresponding phenanthridines 35 300 (Scheme 9) has recently been reported. 25 The 2-vinyl analogues are similarly converted to the corresponding isoquinolines. These outcomes may also be rationalised by a six π-electron cyclisation process.…”

Section: Regioselectivitymentioning

confidence: 99%

Quinoline synthesis: scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes

et al. 2007

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[DO NOT ALTER/DELETE THIS TEXT]Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. paraSubstituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b]quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta [b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo-and thieno-[2,3e]pyridines respectively. Sequential E-to Z-benzylidene group isomerisation and six π-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone Oallyloxime, singlet excited states are involved in both steps.

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New Light-Induced Iminyl Radical Cyclization Reactions of Acyloximes to Isoquinolines

Cited by 163 publications

References 7 publications

Benzyne-mediated rearrangement of 3-(2-pyridyl)-1,2,4-triazines into 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles

Benzyne-mediated rearrangement of 3-(2-pyridyl)-1,2,4-triazines into 10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles

Light-Induced Iminyl Radicals: Generation and Synthetic Applications

Quinoline synthesis: scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes

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