Clarification of Reaction Routes and Synthetic Application regarding Specific Decarbonylative α-Arylation of Carboxylic Acids in Acidic Media

点击翻译按钮获取中文摘要

2-Methoxyalkanoic acids were found to undergo consecutive decarbonylative a, a-diarylation in P2O5-MsOH instead of Friedel-Crafts type arylation on the carbonyl carbon. The influences of the substituents of the arenes and the carboxylic acids in this reaction were elucidated on the basis of the reaction yields. The reaction behavior was found to be primarily governed by the electron-withdrawing/releasing property of the a-substituents on the carboxylic acids as well as the positive species-accepting ability of the arenes. The steric hindrance was shown to participate in determining the reaction feasibility as a secondary factor.Elucidation of the exact reaction behaviors and clarification of reaction routes including rough reaction mechanism for decarbonylative a-arylation of a-ketocarboxylic acids were also performed. In addition, synthetic reaction of novel conjugated molecules from pyruvic acid was investigated.Theme 1 : Clarification of structural requirements of carboxylic acid su … More bstrates for decarbonylative a-arylation. -Influence of the form of a-substituents on reaction behavior and steric and electric effects of the substituents on the aromatic ring were elucidated. Furthermore, semi-quantitative estimation of steric and electric effects of the a-alkyl (a-aryl) groups revealed that the reaction behaviors are divided into 4 types according to the feasibility of decarbonylation and the number of arylation. The relation between the type of the reaction and the structure of a-ketocarboxylic acids is clearly interpreted.Theme 2 : Elucidation of the role of the hetero atoms in condensation mediators. - 2-Methoxypropanoic, methoxyacetic, and methoxyphenylacetic acids were allowed to react with arenes in the presence of phosphorus pentoxide (P2O5), polyphosphoric acid (PPA), methanesulfonic acid mixture (P2O5-MsOH), methanesulfonic acid (MsOH), trifluoromethanesulfonic acid (TfOH), Nafion-H, polyphosphoric acid ethyl ester, or polyphosphoric acid trimethylsilyl ester. As a result, the reaction behavior of decarbonylative a-arylation of a-methoxycarboxylic acids was proved to be strongly dependent on the nature of the acidic mediators. These behaviors were also shown to be characteristic for each mediator. Particularly, the relation between product distribution and the nature of the acidic mediator such as acidity function value evaluated for methoxyacetic acid showed more distinct dependence on the mediator than those of other carboxylic acids. However, general explanation for the whole reaction behavior has not been clarified yet.Theme 3 : Determination of reaction routes and mechanism based on the model reaction of the intermediate candidates. - Clarification of the reaction route has been performed for the reaction of 2- methoxypropanoic acid. Contrarily, investigation on that for methoxyacetic acid revealed that the reaction propagates with different ways from those observed in the reaction of other a-methoxycarboxylic acids. In the reaction of methoxyacetic acid with TfOH, Friedel-Crafts acylation type reaction followed by rearrangement concurrently was observed to propagate along with decarbonylative a-arylation. Less