The title compounds 12, which are key intermediates for antitumoral diazaquinomycin A analogues, are obtained by intramolecular Wittig reaction of 1-[3',6'-dimethoxy-2'-(1~-2(1H)-quinolinones 12 and 17 is examined. oxoacylamino)phenyl]alkyltriphenylphosphonium salts 11, which are prepared via lithiation of 2',5'-dimethoxy-N-pivaloylaniline 6. The applicability of this route to polysubstituted Diazaquinomycin A['], a novel Streptomyces sp. OM-704 metabolite, exhibits promising activity as an antitumor agent but failed to enter human trials because of its insolubility. Nevertheless, diazaquinomycin A is regarded as a novel "lead" compound to design diazaquinomycin congeners, which have currently been synthesized in our group by hetero Diels-Alder cyclizations12] of activated 1 -azadienes 1 with 2,5,8( 1H)-quinolinetriones 2. The dienophiles 2 are readily available by oxidative demethylatiod31 of 5,8-dimethoxy-2( 1H)-quinolinones, which are obtainable by means of several strategied41. The search of preparative routes for 3,4-disubstituted 5,8-dimethoxy-2( 1 H)-quinolinones 12 led us to the utilization of Capuano's 2( 1H)-quinolinone synthesis involving intramolecular Wittig reaction of 2-(a-oxoacylamino)benzyltriphenylphosphonium salts 3 as the key step, where three successful examples were already This reaction is chemoselective in spite of the possible competition between the keto and amide groups, affording 3-substituted 2-quinolinones 4 and 2-acylindoles 5 in a 1O:l ratio. The methods reported for the preparation of 2-amino-3,6-dimethoxybenzaldehyde as the potential starting material for the intramolecular Wittig reaction giving 5,8-dimethoxy-2-quinolinones are tedious and suffered from poor to modest overall yieldsc61. Therefore, we now describe a versatile and efficient method of preparing derivatives 7 and 8 by ortho functionalization of 2,5-dimethoxyaniline. Thus, lithiation of 2',5'-dimethoxy-N-pivaloylaniline 6 (nBuLi, THF, O'C), followed by addition of DMF or the corresponding aldehyde and subsequent reduction of 7, afforded 2'-(1-hydroxyalkyl)-3',6'-dimethoxy-N-pivaloylanilines 8 in good yields. The pivaloyl protecting group was hydrolytically removed by treatment with 10% hydrochloric acid and the free bases 9 were condensed with triphenylphosphonium bromide to afford the phosphonium salts 10, which were acylated with the adequate a-oxoacyl chloride to 11. Since the use of potassium tert-butoxide in the following cyclization step as described by Capuano et al.[5' gave poor results, triethylamine was employed instead. The outcome of the reaction depended on the nature of R1 in 11. The benzyltriphenylphosphonium salts lla-c (R' = H) mainly afforded, 2-quinolinones 12a-c in acceptable yields (25-39%), together with small amounts of 2-acylindoles 13a-c. When derivatives with R' C H were employed, only traces of 12d and 13d (R' = CH3) were detected. In the case of l l e (R' = Ph), 2-acetyl-5,8-dimethoxy-4-phenyl-4H-3,l-benzoxazine 14 was obtained as the only isolable product in 49% yield.Since the method to ...