Cycloadditions of 1-Substituted 1,3-Butadienes with 4- or 3-Substituted 2(1H)-Quinolones Acting as Dienophiles.

Fujita, Reiko; Oikawa, Kanako; Yoshisuji, Toshiteru; Okuyama, Yuko; Nakano, Hiroto; Matsuzaki, Hisao

doi:10.1248/cpb.51.295

Cited by 10 publications

(7 citation statements)

References 22 publications

(22 reference statements)

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“…18 Application of high pressures can be a good way to circumvent the activation problem as cycloadditions are known to be dramatically accelerated under these conditions. 19 Thus, HP's are well suited to cases where the dienophile is poorly reactive, 16 although limitations apply. 20 A good example in which a gem-dimethylcyclopropene plays this part is given below in the 'chiral dienophiles' section (Scheme 23 The regiocontrol observed in the cycloaddition of 1-alkoxydienes to unsymmetrical dienophiles is classically interpreted in terms of preferred interactions between the frontier orbitals with the largest coefficients.…”

Section: Methodsmentioning

confidence: 99%

Selectivity Controls in the [4+2] Cycloadditions of 1-Oxygenated Dienes

Maddaluno¹

2006

Synlett

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Section: Methodsmentioning

confidence: 99%

Selectivity Controls in the [4+2] Cycloadditions of 1-Oxygenated Dienes

Maddaluno¹

2006

Synlett

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“…[14][15][16][17] It is well known that the nitro group function as a leaving group and a strong electron-withdrawing group. Herein, we report the synthesis of 6(5H)-phenanthridones by DA reaction of 3-nitro-2(1H)-quinolones under atmospheric and high pressure (AP and HP) conditions, and we investigate of the reactivity of the 2(1H)-quinolones using molecular orbital (MO) calculation.…”

Section: )mentioning

confidence: 99%

Synthesis of 5(6H)-Phenanthridones Using Diels-Alder Reaction of 3-Nitro-2(1H)-quinolones Acting as Dienophiles

et al. 2006

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2(1H)-Quinolones are classified as aromatic heterocycles.With regard to reactions of 2(1H)-quinolones, substitution reactions [1][2][3][4][5][6][7][8] have been widely reported, but little attention has been focused on addition reactions. Diels-Alder (DA) reaction of 2(1H)-quinolones with diene afforded the phenanthridones in one pot. Recently, Weltin verified the ability of the 6(5H)-phenanthridones to inhibit poly(ADP-ribose)-polymerase (PARP) activity in lymphoma cells. [9][10][11][12] Furthermore, Cheng reported that 8,9-dimethoxyphenanthridinium salts (A, Chart 1) possess activity against leukemias P388. 13)We reported the synthesis of functionalized phenanthridones by novel DA reaction of 1-methyl-2(1H)-quinolones having an electron-withdrawing group (such as methoxycarbonyl, acetyl, cyano) at the 4-or 3-position that acts as a dienophlie.14-17) It is well known that the nitro group function as a leaving group and a strong electron-withdrawing group. Herein, we report the synthesis of 6(5H)-phenanthridones by DA reaction of 3-nitro-2(1H)-quinolones under atmospheric and high pressure (AP and HP) conditions, and we investigate of the reactivity of the 2(1H)-quinolones using molecular orbital (MO) calculation.DA Reaction Firstly, DA reactions of 3-nitro-(1a) and 3,6-dinitro-1-methyl-2(1H)-quinolones (1b) 18,19) with 1,3-butadienes (2a, b) were investigated under AP and HP conditions, as shown in Table 1 and Chart 1. DA reactions of 1a, b with 1-methoxy-1,3-butadiene (2a) were carried out at 180°C for 5 d in o-xylene (entries 1, 4), and gave 6(5H)-phenanthridones (3a, 20) 83%; 3b, 68%), respectively. The same reaction of 3a at 160°C for 3 d (entry 2), also afforded 3a (63%). On the other hand, DA reaction of 1a with 2a was performed under HP conditions (10 kbar) at 90°C for 2 d (entry 3), and gave endo-DA adduct (4a, 57%) and exo-DA adduct (4b, 20%), respectively. Heating of 4a, b at 180°C in sealed tube produced 3a (67%, 64%, respetively) aromatized by elimination of hydrogen and nitrogen dioxide (HNO 2 ), followed by release of MeOH. These facts indicated that 3a, b resulted from release of HNO 2 and MeOH of corresponding DA adducts (such as 4a) under AP conditions. Furthermore, DA reactions of 1a with 2,3-dimethoxy-1,3-butadiene (2b) at 180°C under AP condition gave 1-methyl-8,9-dimethoxy-6(5H)-phenanthridone (6a 3) ; 31%, 45%, entries 5, 6) which was the synthetic intermediate for A possessing a bioactivity. DA reactions of 1b with 2b at 180°C afforded 1-methyl-8,9-dimethoxy-2-nitro-6(5H)-phenanthridone (6b; 17%, 13%, entries 7, 8) in poor yields. But, DA reactions of 1a, b with 2b under HP condition (10 kbar) at 90°C for 2 d afforded DA adducts (5a, 57%; 5b, 55%, entries 9, 10) in reasonable yields. Heating of 5a, b at 180°C produced 6a (48%) and 6b (40%) aromatized by release of HNO 2 , followed by dehydrogenation, respectively. The stereochemistries of the group at C-7 in 4a, b were determined by nuclear Overhauser effect (NOE) measurement of 1 H-NMR spectra. The spectrum of 4a indicated a correlatio...

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“…[16][17][18][19][20][21][22][23][24][25][26][27][28][29] As one of the methodologies, Fujita and co-workers prepared phenanthridine derivatives by Diels-Alder reaction of electron-rich dienes with MeQone having an electron-withdrawing group at the 3 or 4-position. [30][31][32] In our course of study on electron-deficient quinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was found to be highly reactive, which realized direct functionalization of the MeQone.33) The steric repulsion between the 8-nitro and the 1-methyl groups activates the pyridone ring of TNQ, which reveals nitroalkene property rather than aromatic one. …”

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confidence: 99%

“…[4][5][6][7][8][9][10][11][12][13][14][15] From the viewpoint for the drug design, it is also demanded to synthesize hitherto unknown unnatural MeQone derivatives and to develop new methods for functionalization of the MeQone framework. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Especially, modification of the pyridone moiety in the MeQone is highly important because most of the naturally occurring MeQones have substituents at the 3 and/or the 4-position. Mainly used methods for functionalization of the MeQone involve the activation by the pre-introduced substituents such as hydroxyl, alkoxyl and amino groups, [4][5][6][7][8][9][10][11][12][13][14][15] which compose partial structures of newly constructed skeleton.…”

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confidence: 99%

Synthesis of Unnatural 1-Methyl-2-quinolone Derivatives

Asahara

Katayama

Tohda

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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The 1-methyl-2-quinolone (MeQone) skeleton has been found in more than 300 quinoline alkaloids those are mostly isolated from the Rutaceae family. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Since these alkaloids show physiological activities, many researchers have energetically studied the isolation, the structural determination and total syntheses of quinoline alkaloids containing the MeQone skeleton. [4][5][6][7][8][9][10][11][12][13][14][15] From the viewpoint for the drug design, it is also demanded to synthesize hitherto unknown unnatural MeQone derivatives and to develop new methods for functionalization of the MeQone framework. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Especially, modification of the pyridone moiety in the MeQone is highly important because most of the naturally occurring MeQones have substituents at the 3 and/or the 4-position. Mainly used methods for functionalization of the MeQone involve the activation by the pre-introduced substituents such as hydroxyl, alkoxyl and amino groups, [4][5][6][7][8][9][10][11][12][13][14][15] which compose partial structures of newly constructed skeleton. Meanwhile, direct functionalization methods of MeQone were recently attracted. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] As one of the methodologies, Fujita and co-workers prepared phenanthridine derivatives by Diels-Alder reaction of electron-rich dienes with MeQone having an electron-withdrawing group at the 3 or 4-position. [30][31][32] In our course of study on electron-deficient quinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was found to be highly reactive, which realized direct functionalization of the MeQone.33) The steric repulsion between the 8-nitro and the 1-methyl groups activates the pyridone ring of TNQ, which reveals nitroalkene property rather than aromatic one. 34)When TNQ was allowed to react with tertiary amine in acetonitrile, dimer of TNQ connected at the 3-and 4Ј-positions was obtained at room temperature, and denitration on the pyridone ring occurred at the elevated temperature leading to 1.35) On the other hand, 4-functionalized 6,8-dinitro-2-quinolones, were readily formed upon treatment of TNQ with 1,3-dicarbonyl compounds in the presence of triethylamine, in which regioselective C-C bond formation at the 4-position is achieved. 33) Although the present cine-substitution is useful for direct functionalization of the quinolone ring, only 1,3-dicarbonyl compounds were usable. Thus, it is one of the important projects to enable the employment other nucleophiles, which provides a new methodology for the quinolone chemistry. Since we succeed to introduce a variety of acylmethyl groups at the 4-position of the MeQone skeleton, results will be represented in this paper. Results and DiscussionEnamines were employed as the carbon nucleophiles instead of 1,3-dicarbonyl compounds. When TNQ was treated with 1-morpholino-1-phenylethene 2a in the presence of water at room temperature, 4-benzoylmethyl-6,8-dinitro-2-quinolone 3a was isol...

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Cycloadditions of 1-Substituted 1,3-Butadienes with 4- or 3-Substituted 2(1H)-Quinolones Acting as Dienophiles.

Cited by 10 publications

References 22 publications

Selectivity Controls in the [4+2] Cycloadditions of 1-Oxygenated Dienes

Selectivity Controls in the [4+2] Cycloadditions of 1-Oxygenated Dienes

Synthesis of 5(6H)-Phenanthridones Using Diels-Alder Reaction of 3-Nitro-2(1H)-quinolones Acting as Dienophiles

Synthesis of Unnatural 1-Methyl-2-quinolone Derivatives

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