第一部分：吡咯化合物及其衍生物為許多天然物的重要架構，
並擁有重要的生物及藥理活性的重要性。我們提出反應步驟簡單的合成策略，
只要改變反應鹼的使用量及溫度條件就可選擇要合成cis-2,3-雙取代吡喀烷化合物或者是1-H吡喀化合物；
並且反應是經由相當少見的5-endo-tet途徑來生成五環化合物。且在2,3,4-三取代吡喀烷化合物的合成策略，
具有立體化學選擇性的溴化碘加成，以及用鹼(DBU)進行的親核性取代成環反應，
建立了絕佳的立體化學選擇性反應方法；在1-H吡喀化合物的合成策略，
我們利用微波來加速去溴化氫反應的進行，並且與使用甲苯為溶劑加熱迴流反應的條件相比，
大幅提升1-H吡喀化合物的產率。
第二部分：α-亞甲基五環內醯胺(α-Methylene-γ-Lactam)是藥物化學中常見的架構，擁有廣泛的生物活性，例如：抗消炎腫痛性，抗菌性，抗癌活性，抗黴菌性….等生物活性，並且-亞甲基五環內醯胺的毒性比-亞甲基五環內酯還要來的低。過去的文獻報導α-亞甲基五環內醯胺的合成方法並不多，較常見的的方法是利用丙烯基鹵化物與金屬反應生成丙烯基金屬試劑，而後對亞胺化合物進行加成反應，再進行環化反應生成α-亞甲基五環內酯。通常使用的金屬或合金須先活化來生成有機金屬試劑參與反應，造成合成反應條件不易控制。因此我們希望能進行單一步驟反應策略合成α-亞甲基五環內醯胺。我們研發利用烯丙基溴化合物和鋅(1,2-雙碘乙烷當活化劑)與亞胺化合物進行超音波誘導巴比艾爾型式加成反應，可進行位向選擇性與立體選擇性的單一步驟反應模式，以N-甲苯基醯硫基亞胺化合物與丙烯基溴化合物以及金屬鋅（Zn）反應合成一系列cis-雙芳香基-α-亞甲基五環內醯胺。

Part I:
   Nitrogen-containing five-membered heterocycles are one of the most common subunit in many naturally occurring compounds which display diverse and potent biologically activities.  Herewith, we developed a novel and highly diastereoselective cyclization reaction for the preparation of cis-2,3-disubstituted pyrrolidines or 1-H-Pyrroles by using Iodobromide(IBr) and DBU under traditional or microwave-accerlated reaction condition.  Thses reactions mechanism was proved to undergo 5-endo-tet cyclization pathway.  
Part II:
The α-methylene-γ-lactam structure is one of the most common structure which was widely observed in natural products.  It display extensively biological activities such as antiinflammatory, antibacterial, antitumor and antifungal…etc.  
 Only a few examples were reported for the preparation ofα-methylene-lactam. One of the most popular synthetic methodology for synthesis of α-methylene-γ-lactam is the addition reaction of allylmetal to imineand then followed by cyclization reaction.  These reactive metal were 
usually activated in advance to preparaen organometallic reagents and the addition reaction conditions 
usually are tedious and hard to control.  Herewith, we wish to report an one-step synthetic reaction for 
synthesis of α-methylene-γ-lactam.  The cis-stereochemistry of these diaryl-α-methylene-γlactams are achieved by the reaction mixture of zinc, 1,2-diiodoethane, α-bromomethyl acrylate and imine under ultrasound reaction conditions.

目錄
                                                      頁次
中文摘要                                               I
英文摘要                                              III  
第一部分：新型環化反應合成順式2,3-雙取代吡咯烷           1
與1-H-吡咯

第一章 緒論…………………………………….………….…………2
1-1	吡咯化合物及其衍生物的重要性…………………………4
1-1-1 吡咯化合物及其衍生物的生物活性…………………………..5
1-1-2 吡咯烷化合物在不對稱合成上之應用……………………….16
1-2	吡咯烷化合物與1-H-吡咯的合成方法……………………17
1-2-1  分子間反應……………………………………………………18
  1-2-1a  串聯麥可加成反應-過渡金屬催化環化反應……………18
  1-2-1b  1,3-Dipoar環化反應……………………………………19
  1-2-1c  離子碘轉移環化反應…………………………………..20 
1-2-2  分子內環化反應…………………….…………………....21 1-2-2a  自由基環化反應………………………………………....22
  1-2-2b  陰離子環化反應………………………………………….23
  1-2-2c  矽基指導環化反應……………………………………….24
  1-2-2d  分子內碳金屬化反應…….………………………………25
  1-2-2e  親電子性環化反應……………………………………….26
1-3	1-H吡咯化合物的合成方法………………….……………30
1-3-1  由丙二烯系化合物合成………………………………………30
  1-3-1a  [3+2]環化反應……………………………………………30
  1-3-1b  丙二烯系金屬鋰衍生物..………………………………31
  1-3-1c  有機鈀金屬試劑催化偶合環化反應……………………32 
  1-3-1d  金屬離子誘導環化反應……………………………….…32
1-3-2  其它類型………………………………………………………33

第二章 結果與討論………………………………………………….35 
2-1   cis-2,3-雙取代吡咯烷化合物與1-H吡咯化合物的合成....35
2-1-1 cis-2,3-雙取代吡咯烷化合物的合成………………….……37
2-1-2 1-H吡咯化合物的合成….…………………………….………46

2-2	結論…………………………………………………..……49

第三章 實驗與儀器……………………………………………………52
3-1	實驗儀器與溶劑乾燥………………………………………52
3-1-1 實驗儀器與測試方法.…………………………………………52
3-2-1  溶劑的乾燥………………………………….……………….54
3-2 一般反應條件與實驗步驟…………………………….…………55

附錄一  第一部分光譜…………………………………….…………58

參考資料…………………………………………………..…………144
  
第二部分：超音波促進巴比艾爾形式反應合成順式雙芳香基α-亞甲基五環內醯胺

第四章 緒論………………………………………………………...150
4-1    α-亞甲基五環內醯胺之重要性………………………...…150
4-1-1  α-亞甲基五環內醯胺的生物活性…….……………………151
4-2    α-亞甲基五環內酯的合成方法………………………….…154
4-2-1 丙烯基溴金屬試劑與亞胺化合物反應………………………155
4-2-2 分子內成環反應………………………………………………158
4-3   超音波在有機合成上之應用……………………………....161
4-3-1 超音波的基本概念…………………………………….…….162
4-3-2 實驗室常用的超音波裝置………………….…………….…168
4-3-3 超音波在合成上的應用………………………………..……171

第五章 結果與討論.…………………………………….………...178
5-1	金屬活化方法之探討……………………………….……178
5-2	超音波誘導巴比艾爾型式反應…………………….……182
5-2-1    亞胺化合物N-取代基對加成反應選擇性之影響…….…183
5-2-2    α-亞甲基五環內醯胺的合成……………………….……185
5-3	結論…….…………………………………………….….187

第六章 實驗與儀器……………………………………………...…188
6-1   實驗儀器與溶劑乾燥………………………………....……188
6-1-1 實驗儀器與測試方法.………………………………….……188
6-1-2  溶劑的乾燥.………………………………………….…….190
6-2 一般反應條件與實驗步驟………..……………………..……190

附錄二  第二部分光譜……………………………………….…….192

參考資料……………………………………………………........227

作者著作………………………………………………………….…231

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