(1)Microwave and Ultrasound Accelerated Synthesis of 5-Cyanoindole (2)Synthesis and the Synthetic Applications of a New Chiral Hydrazine Auxiliary

本論文分為兩個部份: (一)利用微波與超音波加速5-氰基吲哚之合成 此部分報導我們使用微波與超音波大幅縮短以Russell的方法合成5-氰基吲哚之反應時間。我們使用田口法尋找最佳條件，將傳統上需要20小時之加熱的反應以微波照射3分鐘或超音波照射8分鐘，即可以得到高產率之5-溴基吲哚。此外，我們也成功地利用微波加速5-溴基吲哚之氰化反應，由18小時之傳統加熱縮短為6分鐘。我們的反應條件可大幅縮短反應時間，在工業上可大幅提高設備使用率、減低能源消耗，因此極具產業經濟價值。 (二)新掌性聯胺輔助體之合成與其在有機合成上的應用 此部分報導我們使用(+)-莰烯當起始物，經由四個步驟合成一個新掌性聯胺輔助體，N-胺基-10,10-二甲基-4-三雜環-[5,2,1,01,5]癸烷，其總產率為54%。而後將此聯胺與一系列的醛類於室溫下進行縮合反應，即可得到相對應的腙掌性模板。最後，此掌性模板於 –40ºC下與正丁基鋰進行不對稱之烷基化反應，得到產率為94% 至98% 之具光學活性的聯胺，其非鏡像超越值為58% 至89%。This thesis consists of two parts: (1)Microwave and Ultrasound Accelerated Synthesis of 5-Cyanoindole We have developed a practical and efficient synthesis of 5-cyanoindole based on Russell's process using microwave and ultrasound irradiation. Taguchi method was used to optimize the reaction conditions for achieving the highest yield of 5-bromoindole. The hydrolysis of sodium 1-acetylindoline-5-bromo-2-sulfonate was accomplished in 3 min and 8 min under microwave irradiation and ultrasonic irradiation respectively as compared to the 20 h conventional reflux method. Furthermore, the microwave-assisted cyanation of 5-bromoindole was accomplished in 6 min versus more than 18 h of thermal heating. Our methods can dramatically reduce the reaction time which, in turn, can increase the turn over rate of production equipment and decrease energy consumption and hence have economic value. (2)Synthesis and the Synthetic Applications of a New Chiral Hydrazine Auxiliary A novel synthetic approach for the preparation of the a chiral hydrazine auxiliary, N-amino-10,10-dimethyl-4-azatricyclo-[5,2,1,01,5]decane, from (+)-camphene in four steps (54% overall yield) has been established. The chiral hydrazone templates were obtained via the condensation of aldehydes and the hydrazine at room temperature. Finally, the hydrazones were stereoselectively alkylated with n-butyllithium at -40ºC to give optically active hydrazines in up to 94%~98% and 58%~89% de.中文摘要…………………………………………………………iii 英文摘要…………………………………………………………iv 壹、緒論 第一節 利用微波與超音波加速5-氰基吲哚之合成……………1 一、5-氰基吲哚及其衍生物的傳統合成方法…………………1 二、微波在有機合成上之應用…..……………………………5 三、超音波在有機合成上之應用………………………………14 四、田口法在有機合成上之應用………………………………19 第二節 新掌性聯胺輔助體之合成與應用………………………23 貳、結果與討論 第一節 利用微波與超音波加速5-氰基吲哚之合成…………44 一、由吲哚合成吲哚琳亞硫酸鈉………………………………44 二、利用微波及超音波加速5-溴基吲哚之合成………………46 三、利用微波加速5-氰基吲哚之合成…………………………53 第二節 新掌性聯胺輔助體之合成與應用……………………56 一、掌性輔助體的製備…………………………………………56 二、Hydrazone的合成……………………………………………59 三、Hydrazone的應用……………………………………………61 參、參考資料……………………………………………………66 肆、藥品與儀器…………………………………………………73 伍、實驗步驟與化合物光譜……………………………………7