基于二烯酮的双亲核加成-硫醚化新反应研究

The development of new reactions and new synthetic strategies is one of the important and challenging tasks in organic synthetic chemistry. Recently, as part of our research on the synthesis of trifluoromethyl-containing compounds, a methyl aryl sulfide, 2-(5-(methylthio)-2-(trifluoromethyl)phenyl)-1-phenylethanone, was obtained from the reaction of 4-(trifluoromethyl)-4-(trimethylsilyloxy)cyclohexa-2,5-dienones and 3,3-bis(methylthio)-1-phenylprop-2-en-1-one in the presence of catalytic amount of a cheap Lewis acid via double nucleophilic addition-thioetherification sequence (with alpha-carbon of 3,3-bis(methylthio)-1-phenylprop-2-en-1-one and the methylthiol formed in the reaction as nucleophiles, respectively). This reaction proceeds under mild reaction conditions without the use of odorous thiols and provides a new route for the synthesis of trifluoromethylated aryl sulfides in one-pot from easily available starting materials. More importantly, the thioetherification involved in this double nucleophilic addition reaction was found for the first time and thus provided a new route to benzenethioethers bearing a trifluoromethyl group. This project is to study this new reaction especially for the formation of C-S bond in details, including the reaction mechanism and the scope of the double nucleophilic addition-thioetherification reaction.

发现新反应和新合成途径是有机合成化学的主要任务之一，富有挑战性。最近, 本课题组在研究含三氟甲基有机化合物的合成方法时发现，在Lewis酸催化下，4-(三氟甲基)-4-(三甲硅氧基)-环己二烯-2,5-二酮和alpha-苯甲酰基二甲硫缩烯酮反应生成2-[5-(甲硫)-2-(三氟甲基)苯基-1-苯乙酮。该反应不仅提供了一种从易得原料出发一步合成含三氟甲基苯基硫醚的新途径，且具有诸如反应条件温和、避免使用具有难闻气味的硫醇等优点。更为重要的是，反应涉及到在双亲核加成过程中（分别以alpha-苯甲酰基二甲硫缩烯酮的alpha-碳原子和反应中生成的甲硫醇为亲核体），羰基和硫醇反应转化为硫醚的新反应。本项目以此为基础，拟在对反应机理加以详细研究的基础上，对这类新反应加以详细研究。

发现新反应和新合成途径是有机合成化学的主要任务之一，富有挑战性。由于含三氟甲基有机化合物在医药、农药等领域得到日益广泛的应用，向有机化合物中引入三氟甲基的合成方法学研究已成为令人关注的重要研究领域。本项目以我们发现的Lewis 酸催化的4-(三氟甲基)-4-(三甲硅氧基)-环己二烯-2,5-二酮和 alpha-苯甲酰基二甲硫缩烯酮生成2-[5-(甲硫)-2-(三氟甲基)]苯基-1-苯乙酮的反应为契机，发展了一些从易得原料出发，温和、高效地向有机化合物中引入三氟甲基的新方法；对二烯酮的双亲核加成–硫醚化合成策略进行了深入系统的研究，并对反应类型进行了多方面扩展。项目执行期间发表了多篇学术论文和发明专利，较好地完成了项目课题。本项目为拓展该类反应在有机合成中的应用提供了理论和实验基础。