臺灣博碩士論文加值系統

摘要
炔類在藥物化學與有機合成上是個極為重要的官能基團，近年來利用末端炔類和芳香鹵化物經由過渡金屬進行交互耦合反應是最有效的方法。而其中以鈀與銅金屬共催化又稱為Sonogashira反應為最普遍，然而鈀金屬具有高毒性且昂貴，利用極便宜且低毒性銅金屬作為催化劑的Sonogashira反應是近年來極被重視的研究主題。最近本實驗室發展出利用催化量(1 mol %)氧化亞銅搭配雙牙基的磷配體可以有效促進Sonogashira反應，得到高產率的多樣化炔類化合物。
最近的報導指出烯基硫醚化合物可以對抗肺結核、炭疽熱和其他革蘭氏陽菌的抗藥性，利用硫醇和炔類化合物經由自由基的加成反應製成這類化合物是常見的策略，但缺點是會產生非目標物的位置異構物。過渡金屬催化硫醇或硫酚與烯基鹵化物的交互耦合反應是一重要的方法合成這類化合物。文獻上，鈀、鈷與銅曾經被報導用來促進這類反應，本論文的第二部分我們發現第一個利用無毒性並且極便宜的鐵金屬與雙牙基磷配體，可以有效促進交互耦合反應。

Abstract

The acetylenic compounds are important building block in the fields of pharmaceutical chemistry and organic synthesis. The transition metal catalyzed coupling reaction of terminal alkynes with aryl halides has become one of the most important methods for preparing functionalized alkynes. Palladium and copper co-catalyzed system is well known as Sonogashira reaction, however, palladium is not only expensive but also highly toxic. Thus, develop the system by using copper as the sole metal source has gain much attention in recent years. The first part of this thesis, we report a highly efficient catalytic system employs the combination of Cu2O (1 mol %) with bisphosphine ligand, giving the products in good to excellent yields.
Recently, aryl vinyl sulfides have been reported as drug candidates against drugresistant strains of tuberculosis and anthrax, in addition to many other drug-resistant Gram-positive bacteria. Addition of thiols to alkynes through a radical pathway is a common way to prepare these compounds, however, this method will produce the undesired regioisomers at the same time. Transition metals including palladium, cobalt and copper have been reported for coupling reaction of thiols with vinyl halides. The second part of this thesis, we report the first iron-catalyzed coupling reaction of thiols with vinyl halides in the presence of a bisphosphine ligand, giving the aryl vinyl sulfide in good yields.

目錄
摘要…………………………………………………………………i
英文摘要……………………………………………………………ii
表目錄……………………………………………………………………vi
圖目錄…………………………………………………………………vii
一、序論…………………………………………………………………1
(一) 過渡金屬之交互耦合反應…………………………………… 1
(二) Sonogashira 耦合反應……………………………………4
(三) 碳-硫鍵交互耦合反應…………………………………………11

二、研究動機……………………………………………………………17
(一) 銅金屬催化Sonogashira反應…………………………………17
(二) 鐵催化乙烯基鹵化物與硫醇之交互耦合反應………………19

三、結果與討論…………………………………………………………21
(一) 銅金屬催化Sonogashira反應…………………………………21
(二) 結論與展望……………………………………………………26
(三) 鐵催化乙烯基鹵化物與硫醇之交互耦合反應………………27
(四) 結論與展望……………………………………………………38


四、儀器設備與藥品溶劑……………………………………………39
五、實驗步驟…………………………………………………………41
六、光譜數據…………………………………………………………47
七、參考資料………………………………………………………76
八、NMR光譜………………………………………………………80

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