四氫噻吩 (tetrahydrothiophene derivatives) 常見於天然物的結構中；這些具生物活性的四氫噻吩天然物可作為藥劑治癒疾病，同時四氫噻吩衍生物可作為奈米材料，賦予材料不同的性質，並且可作為配位基幫助化學反應的進行。現今文獻中四氫噻吩衍生物通常利用 Prins Cyclization、Michael/ Aldol reaction、路易斯酸催化、金屬催化等方式合成，而本實驗室以具 diallyl sulphide 結構的反應物藉由釕金屬催化閉環複分解反應合成出四氫噻吩單元，並以 Claisen 和 Overman rearrangement 進行衍生化，更進一步地欲使其形成具 cyclopenta[c]thiophene 結構的雙環四氫噻吩衍生物，但藉由 ene-carbonyl reaction、Prins cyclization、Cu(I)-mediated halogen-atom-transfer radical cyclization…等方式進行雙環四氫噻吩的合成，均無法獲得雙環四氫噻吩產物，原因可能在於環張力過大或是四氫噻吩中的硫原子使過渡金屬催化劑喪失活性，因此後續藉由格林納試劑修飾官能基使其具備 allyl acetate 結構後，最終以釕金屬催化進行閉環複分解反應建立雙環四氫噻吩結構。

Tetrahydrothiophene derivatives are commonly found in the structures of natural products, these biologically active tetrahydrothiophene derivatives can be used as medicinal drugs. Tetrahydrothiophene derivatives also can be used in nanomaterials and assist asymmetric organic synthesis. In the past literatures, synthesis methods such as Prins cyclization, Michael/ aldol reaction, Lewis acid catalysis, transition metal catalysis have been used by chemists to synthesize tetrahydrothiophene derivatives. In this thesis, a strategy based on the ring closing metathesis of functionalized diallyl sulfides to synthesize tetrahydrothiophene was proposed. Further utilization of Claisen / Overman rearrangement to modified its functional groups should allow the synthesis of bicyclic tetrahydrothiophene. A number of methods were attempted to synthesize bicyclopenta[c]thiophene derivatives, these including ene-carbonyl reaction, Prins cyclization, Cu(I)-mediated halogen-atom-transfer radical cyclization. However non of these reactions were successful. We infer that when synthesizing bicyclopenta[c]thiophene, the ring strain is perhaps too high to allow bicyclopenta[c]thiophene formation, or that sulfur atom could cause the loss of catalytic activity in transition metal-catalyzed reactions. Thus we converted the tethered aldehyde into allyl acetate with Grignard reagent and finally constructed the bicyclopenta[c]thiophene structure by ring-closing metathesis.

論文審定書 i
論文公開授權書 ii
致謝 iii
中文摘要 iv
Abstract v
目次 vi
圖目錄 ix
流程目錄 xi
表目錄 xii
光譜目錄 xiii
縮寫表 xv
第一章 緒論 1
1.1 研究背景 1
1.1.1 四氫噻吩衍生物 (Tetrahydrothiophenes) 簡介 1
1.2 四氫噻吩衍生物合成方法介紹 3
1.2.1 用 Prins Cyclization合成四氫噻吩 3
1.2.2利用Michael/ Aldol reaction 合成四氫噻吩 6
1.2.3利用路易斯酸催化合成四氫噻吩衍生物 12
1.2.4利用金屬催化劑合成四氫噻吩 19
1.3 研究動機及實驗設計 24
第二章 實驗結果與討論 28
2.1 (2,5-Dihydrothiophen-3-yl)methanol (38) 合成 28
2.1.1 2-Methylenepropane-1,3-diol (32) 之合成 28
2.1.2 5-Methylene-2- oxo [1,3,2] dioxathiane (33) 之合成 29
2.1.3 2-((Allylthio)methyl)prop-2-en-1-ol (35) 之合成 30
2.1.4 (2,5-Dihydrothiophen-3-yl)methanol (38) 之合成 31
2.2 利用 Overman rearrangement 合成 acetamide 33
2.2.1 Trichloroacetimidate (39) 之合成 33
2.2.2 利用傳統加熱進行 Overman rearrangement 33
2.2.3 利用微波加熱進行 Overman rearrangement 35
2.3 利用 Claisen rearrangement 合成 aldehyde 37
2.3.1以鈀金屬催化合成 3-((vinyloxy)methyl)-2,5-dihydrothiophene (41) 37
2.3.2 利用微波加熱進行 Claisen rearrangement 38
2.3.3 利用掌性催化劑進行具位向選擇性 Claisen rearrangement 49
2.4 對功能性四氫噻吩進行衍生化合成雙環四氫噻吩 40
2.4.1 利用 ene-carbonyl reaction 合成雙環四氫噻吩 40
2.4.2 利用 Prins cyclization 合成雙環四氫噻吩 43
2.4.3 在酸性催化下令 hydroxyl group 對分子內 alkene 進行加成 44
2.4.4 利用 Cu(I)-mediated halogen-atom-transfer radical cyclization 合成雙環四氫噻吩 45
2.4.5 利用格林納試劑對 aldehyde (42) 進行衍生化 46
2.5 結論 48
第三章 引用文獻 49
第四章 實驗步驟與光譜數據 53
4.1 儀器設備與藥品材料 53
4.2 合成步驟與數據 56
第五章 光譜資料 70

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