Synthesis of unsymmetrical and regio-defined 2,3,6-quinoxaline and 2,3,7-pyridopyrazine derivatives

Sherman, Dan; Kawakami, Joel K.; He, Hongwu; Dhun, Farah; Rios, Raphael; Liu, Hu; Pan, Wei; Xu, Yong‐Jiang; Hong, Sang-phyo; Arbour, Mélissa; Labelle, Marc; Duncton, Matthew A. J.

doi:10.1016/j.tetlet.2007.10.117

Cited by 17 publications

(6 citation statements)

References 23 publications

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“…An intermediate amide was also observed by Sherman et al [33] in the reaction between an α-ketoacid, thiophene-2-glyoxylic acid, and N -(2-amino-4-nitrophenyl)acetamide, in accordance with the mechanism proposed in this work.…”

Section: Resultssupporting

confidence: 91%

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

Campos¹,

Rodrigues²,

Belladona³

et al. 2017

Beilstein J. Org. Chem.

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The syntheses of several polyazaheterocycles are demonstrated. The cyclocondensation reactions between β-enaminodiketones [CCl3C(O)C(=CNMe2)C(O)-CO2Et] and aromatic amidines resulted in glyoxalate-substituted pyrido[1,2-a]pyrimidinone, thiazolo[3,2-a]pyrimidinone and pyrimido[1,2-a]benzimidazole. Pyrazinones and quinoxalinones were obtained through the reaction of these glyoxalates with ethylenediamine and 1,2-phenylenediamine derivatives. On the other hand, the reaction of glyoxalates with amidines did not lead to the formation of imidazolones, but rather N-acylated products were obtained. All the products were isolated in good yields. DFT-B3LYP calculations provided HOMO/LUMO coefficients, charge densities, and the stability energies of the intermediates, and from these data it was possible to explain the regiochemistry of the products obtained. Additionally, the data were a useful tool for elucidating the reaction mechanisms.

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Section: Resultssupporting

confidence: 91%

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

Campos¹,

Rodrigues²,

Belladona³

et al. 2017

Beilstein J. Org. Chem.

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“…An unusual palladium‐catalyzed selective arylation of an activated CCl bond in the presence of an activated CBr bond was reported by Sherman et al 194. in 2007.…”

Section: Cross‐coupling Reactions Of Polyhalogenated Heterocycle‐anmentioning

confidence: 85%

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

2012

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The palladium-catalyzed Suzuki-Miyaura reaction of multiply halogenated, electron-rich and electron-deficient heteroarenes is one of the most reliable and environmentally friendly tools for installing a wide range of non-functionalized and functionalized carbon substituents onto heteroaromatic systems with exquisite chemo-and site-selectivity. For substrates with different halogen groups the chemoselectivity of the Suzuki-Miyaura reactions has been found to be dependent on the reactivity difference between the halogens. However, the hardest achievement of selectivity in Suzuki-Miyaura monocouplings involving polyhalogenated heteroarenes with identical halogen atoms has been shown to be dominated by steric and electronic effects and the presence of directing groups at positions neighbouring the reaction sites. Moreover, in the case of symmetrically substituted dihaloheteroarenes with identical halogen atoms, highly selective monocoupling reactions have often been achieved only after a careful optimization of reaction parameters including the catalyst precursor, base, solvent, and the molar ratio between electrophile and organoboron reagent. This critical review with 341 references covers developments on the chemo-and site-selective Suzuki-Miyaura monocoupling reactions of polyhalogenated heteroarenes with different or identical halogen atoms. It also includes the synthesis of polysubstituted heteroarenes, not easily accessible by other means, via consecutive monocoupling reactions and/ or a more synthetically valuable approach involving one-pot polycoupling reactions.

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“…Sherman et al prepared the opposite regioisomer 26 (SYN) by masking the more reactive amino group in 11f through the acetamide intermediate 25 and its subsequent reaction with acid chloride 24 , forming a stable N -acetamide- N’ -acylamide intermediate (not shown). The acetamide group was then selectively cleaved and the liberated amino group spontaneously cyclised to SYN quinoxalin-2(1 H )-one 26 [ 27 ] ( Scheme 4 ).…”

Section: Introductionmentioning

confidence: 99%

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

Dobiáš¹,

Ondruš²,

Addová³

et al. 2017

Beilstein J. Org. Chem.

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3-Acylmethylidene-3,4-dihydroquinoxalin-2(1H)-ones are compounds which possess a wide range of physical and pharmaceutical applications. These compounds can be easily prepared by cyclocondensation of o-phenylenediamines and aroylpyruvates. Unsymmetrically substituted o-phenylenediamines can be obtained form regioisomeric mixtures of 3,4-dihydroquinoxalin-2(1H)-ones. It is often quite difficult to get a pure regioisomer and determine its structure without controlling the reaction selectivity and exploitation of complex NMR techniques (HSQC, NOESY, HMBC). This article examines the regioselectivity of the cyclocondensation between six monosubstituted o-phenylenediamines (-OMe, -F, -Cl, -COOH, -CN, -NO2) and the derivatives of p-chlorobenzoylpyruvate (ester or acid) which we studied. Six regioisomeric 3,4-dihydroquinoxalin-2(1H)-one pairs were selectively prepared and characterised. Based on our experiences, a simplified methodology for determining the structure of the regioisomers was proposed. We developed two general and highly selective methodologies starting from the same o-phenylenediamines and activated 4-chlorobenzoylpyruvates (ester or acid) enabling switching of 3,4-dihydroquinoxalin-2(1H)-one regioselectivity in a predictable manner. For comparison, all regioselective cyclocondensations were performed with the same standardized conditions (DMF, rt, 3 days), differing only by the additives p-TsOH or HOBt/DIC (hydroxybenzotriazole/N,N’-diisopropylcarbodiimide). Both selected methods are simple, general and highly regioselective (72–97%). A mechanism for the regioselectivity was also proposed and discussed. This study can be used as a guide when choosing the most optimal reaction conditions for the synthesis of the desired 3,4-dihydroquinoxalin-2(1H)-one regioisomers with the best selectivity. The demonstrated methodologies in this article may also be applied to differently substituted 3,4-dihydroquinoxalin-2(1H)-ones in general, which could expand the synthetic impact of our results.

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Synthesis of unsymmetrical and regio-defined 2,3,6-quinoxaline and 2,3,7-pyridopyrazine derivatives

Cited by 17 publications

References 23 publications

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

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