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

有机催化合成光学活性季碳的方法及其在生物活性化合物合成中的应用

• 批准号: 17590023
• 负责人: HARA Osamu
• 金额: $ 2.48万
• 依托单位: Meijo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590023/
• 关键词: Stetter reaction; azolium salts; Heck reaction; biphenyl thiazolium salts; fluorous catalyst; quarternary carbon; Setter反応; 4級炭素構造; フルオラス化合物; 4級炭素構築; β-ヒドロキシ-α-アミノ酸

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.

噻唑是最重要的杂芳烃之一，具有重要的药用价值，是噻唑盐的起始原料，作为有机催化剂的用途引起了人们的关注。噻唑与芳香族卤化物或三氟酸盐直接偶联是制备衍生噻唑的较好方法，其合成简单。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三氟化联芳酯的直接交叉偶联反应，得到了2-芳基噻唑。2-三甲基硅基噻唑是钯催化的直接交叉偶联反应的有效对应物，无需任何氟阴离子源即可得到2-芳基噻唑。由5-（2-羟乙基）-4-甲基噻唑与氯化苄驱动的噻唑盐通常用作Stetter反应的催化剂。我们成功地用氟化学方法从5-（2-羟乙基）-4-甲基噻唑制备了可重复使用的噻唑盐。通过与含氟苄基卤化物类似物的四季化，在该噻唑的羟基和噻唑环的氮原子上引入了含氟标签。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，含氟催化剂的产率达到82%。含氟催化剂在分子间Stetter反应中存活了5个循环。