臺灣博碩士論文加值系統

(I)本實驗室開發出一個不使用鈀金屬和配位基催化的三步一鍋化反應，此催化系統是利用氯化銅來取代鈀金屬的使用，其有便宜和容易從產物中移除的優點，同時可方便應用於合成出一系列苯駢[b]噻吩衍生物。

(II)本實驗室開發的一鍋三步化反應，已成功應用於雷洛昔芬之合成，合成過程有7個步驟，總產率約21%。起始物使用2-碘-5甲氧基苯硫醚55經過碘化反應得到化合物56，緊接著利用氯化銅催化一鍋三步化反應做為關鍵步驟得到化合物58，最後經過格林納加成反應、去甲氧基保護和親核性芳香環取代反應得到雷洛昔芬62。

(I)A palladium- and ligand-free reaction condition for Sonogashira-type coupling was developed, which used CuCl2 as the catalyst system and was applicable to one-pot three-steps synthesis of benzo[b]thiophene derivatives. Since this catalyst is cheap and easily removable (by washing), it may have some practical usage for chemists.

(II)Total synthesis of raloxifene was accomplished in seven steps in 21% of total yields. This novel route was starting from the corresponding thioanisole 55. The iodination of compound 55 by treating with NIS in the presence of TMSCl can provide the 46% yield of the desired iodothioanisole 56. After the CuCl2-promoted one-pot three-step protocol was employed to iodothioanisole 56 as the key step for the construction of benzo[b]thiophene skeleton 58, the further three steps were carried out via Grignard reagent addition, deprotection, and SNAr reaction to afford the raloxifene 62.

謝誌------------------------------------------------------i
中文摘要-------------------------------------------------iii
Abstract---------------------------------------------------v
目錄-----------------------------------------------------vii
Scheme目錄----------------------------------------------viii
圖表目錄---------------------------------------------------ix
第壹章、緒論-------------------------------------------------1
第一節、過渡金屬催化耦合反應---------------------------------3
第二節、銅金屬催化交互耦合反應-------------------------------7
第三節、苯駢[b]噻吩(Benzo[b]thiophene)分子合成的簡介--------11
第四節、鹵化芳香烴(Aryl halides)氰化之介紹------------------15
第五節、Sonogashira耦合反應之簡介--------------------------22
第六節、雷洛昔芬(raloxifene)之介紹-------------------------29
第貳章、研究目的--------------------------------------------36
第參章、實驗結果與討論----------------------------------------38
第一節、三步一鍋化反應-------------------------------------38
第二節、雷洛昔芬之合成研究---------------------------------46
第肆章、結論與展望-------------------------------------------52
第伍章、實驗步驟與光譜數據------------------------------------53
第陸章、儀器設備及試劑----------------------------------------71
第柒章、參考文獻--------------------------------------------73
第捌章、NMR光譜數據-----------------------------------------81

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