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

发现2-甲氧基烷酸在P_2O_5-MSOH中发生了连续的a，a-二芳基化反应，而不是在羰基碳上发生Friedel-Craft型芳基化反应。以反应产率为基础，讨论了芳烃取代基和羧酸取代基对反应的影响。反应行为主要由α-取代基在羧酸上的吸电子/释放性能和芳烃的正物种接受能力决定。空间位阻作为次要因素参与了反应可行性的确定，并对具体的反应行为进行了总结，澄清了反应路线，包括α-酮羧酸脱羧α-芳基化反应的粗略反应机理。此外，还研究了以丙酮酸为原料合成新型共轭分子的反应。主题1：明确了羧酸su…的结构要求更多的bstrates用于脱羰基α-芳基化。阐述了α-取代基形态对反应行为的影响以及取代基在芳环上的空间和电学效应。此外，对α-烷基(a-芳基)基团的空间效应和电学效应的半定量估算表明，根据脱羰基的可行性和芳基化次数，反应行为可分为4种类型。清楚地解释了反应类型与α-酮羧酸结构之间的关系。主题2：阐明杂原子在缩合中间体中的作用。-2-甲氧基丙酸、甲氧基乙酸和甲氧基苯基乙酸在五氧化二磷(P2O5)、多聚磷酸(PPA)、甲烷磺酸混合物(P2O5-MSOH)、甲烷磺酸(MSOH)、三氟甲磺酸(TfOH)、Nafion-H、多聚磷酸乙酯或多聚磷酸三甲基硅酯的存在下与芳烃反应。结果表明，α-甲氧基羧酸的脱羰α-芳基化反应行为强烈地依赖于酸性介体的性质。这些行为也被证明是每个调解人的特征。特别是，产物分布与酸性介体性质的关系，如甲氧基乙酸的酸度函数值，显示出比其他羧酸更明显的依赖于介体。然而，对整个反应行为的一般解释还没有得到澄清。主题3：基于中间体候选的模型反应确定反应路线和反应机理。-对2-甲氧基丙酸的反应路线进行了澄清。相反，对甲氧基乙酸的研究表明，该反应以不同于其他α-甲氧基羧酸反应的方式进行。在甲氧基乙酸与TfOH的反应中，观察到Friedel-Craft型酰化反应和重排反应伴随着脱羰基α-芳基化反应的进行。较少

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