Development of the synthetic method for an optically active quarternary carbon by the use of organocatalysis and its application for the synthesis of biologically active compounds

噻唑类化合物是一类重要的杂环化合物，具有重要的药用价值，也是合成噻唑盐的原料，作为有机催化剂的应用引起了人们的关注。噻唑类化合物与芳香族卤化物或三氟化物直接偶联，由于合成简单，是一种较好的合成方法。在手性噻唑盐的合成研究过程中，我们遇到了钯催化的2-三甲基硅基噻唑与联芳基三氟酸酯的交叉偶联反应，得到了2-芳基噻唑。2-三甲基硅基噻唑是钯催化的芳香族三氟化合物直接交叉偶联反应的有效对映体，不需要任何氟离子来源即可得到2-芳基噻唑。5-(2-羟乙基)-4-甲基噻唑与氯化苄反应生成的噻唑盐通常被用作Stetter反应的催化剂。以5-(2-羟乙基)-4-甲基噻唑为原料，用氟化学方法成功地制备了可重复使用的噻唑盐。通过与氟基苯卤化物的季胺化，将氟标记引入到该噻唑的羟基和噻唑环的氮原子上。氟噻唑盐的合成用途与标准催化剂相似。在分子内Stetter反应中，用氟催化剂以82%的产率合成了目标产物。此外，氟催化剂在分子内Stetter反应中也存活了5个循环。

Thiazloes are among the most important heteroaromatics with pharmaceutical importance and as starting material of thiazolium salts, which attract the attention for the utility as organocatalysts. Direct coupling of thiazoles with aromatic halides or triflates is preferable method for preparation of derivatized thiazoles in terms of its synthetic simplicity. In the course of the synthetic study on chiral thiazolium salts, we encountered direct palladium-catalyzed cross-coupling reaction of 2-trimethylsilylthiazoles with biaryl triflates leading to 2-arylthiazoles. 2-Trimethylsilylthiazoles serve as an efficient counterpart for direct palladium-catalyzed cross coupling reaction with aromatic triflates without any fluoride anion source to afford 2-arylthiazoles.Thiazolium salts drived from 5-(2-hydroxyethyl)-4-methylthiazole with benzyl chloride have generally been used as the catalyst for the Stetter reaction. We have succeeded in preparing the reusable thiazolium salts from 5-(2-hydroxyethyl)-4-methylthiazole with fluorous chemistry. The fluorous tags were introduced into the hydroxyl group of that thiazole and the nitrogen atom of thiazole ring by its quarternisation with fluorous benzylhalide analogue. The synthetic utility of the fluorous thiazolium salts was similar to that of the standard catalyst. In the intramolecular Stetter reaction, the desired product was produced in 82% yield by the use of the fluorous catalyst. Also, the fluorous catalyst survived 5 cycles in the intromolecular Stetter reaction.