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...
