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Author: 林思廷
Lin, Ssu-Ting
Thesis Title: 二溴亞鐵輔佐4-炔醯胺環己-2-烯-1-酮分子內麥可加成反應:稠環γ-內醯胺化合物的合成
Synthesis of Bicyclic γ-Lactams via FeBr2-Mediated Michael-Addition of 4-Ynamido-Tethered Cyclohex-2-en-1-one
Advisor: 葉名倉
Yeh, Ming-Chang
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2020
Academic Year: 108
Language: 中文
Number of pages: 197
Keywords (in Chinese): 溴化亞鐵炔醯胺分子內麥可加成稠環γ-內醯胺
Keywords (in English): iron(II) bromide, ynamide, Michael-Addition, fused bicyclic γ-lactams
DOI URL: http://doi.org/10.6345/NTNU202000576
Thesis Type: Academic thesis/ dissertation
Reference times: Clicks: 107Downloads: 3
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  •   本文探討路易士酸輔佐4-炔醯胺環己-2-烯-1-酮分子內環化反應,合成含氮γ-內醯胺化合物。使用4-炔醯胺環己-2-烯-1-酮為起始物,以四氫呋喃為溶劑在氮氣下,溴化亞鐵先活化炔醯胺而得到keteniminium中間體A,而溴陰離子加成至keteniminium 中α位置的碳上而得到中間體B,再進行分子內麥可加成環化反應,得到含三個連續立體中心的稠環γ-內醯胺化合物。此反應的優點是操作簡單、產率高、得到唯一的立體異構物、好的官能基容忍度與溫和的條件且不需添加額外的氧化劑就可以合成稠環γ-內醯胺化合物。

    關鍵字:溴化亞鐵、炔醯胺、分子內麥可加成、稠環γ-內醯胺。

    A novel synthesis of fused bicyclic γ-lactams is developed. Treatment of iron(II) bromide with 4-ynamido-tethered cyclohex-2-en-1-ones in THF under nitrogen proceeded via Michael-Addition to afford fused bicyclic γ-lactams in good yields. Activation of the ynamide with FeBr2 gives a keteniminium intermediate A. Addition of a bromide at the α-position of the keteniminium ion affords intermediate B which undergoes intramolecular Michael-Addition to give the fused bicyclic γ-lactams with three contiguous stereocenters after hydrolysis. The reactions are procedurally simple, excellently diastereoselective and high yielding, producing fused bicyclic γ-lactams under mild conditions without an additional oxidizing reagent.

    Keywords: iron(II) bromide, ynamide, Michael-Addition, fused bicyclic γ-lactams.

    謝誌 I 摘要 III Abstract IV 目錄 V 表目錄 VII 圖目錄 VIII 流程目錄 IX 縮寫列表 XI 一、緒論 1 二、文獻回顧 4 1. 稠環γ-內醯胺的合成方法學 4 2. 炔醯胺化合物的分子內合環反應 8 3. 鐵催化分子內合環反應 11 三、實驗結果與討論 15 1. 實驗設計 15 2. 合環前起始物III-5的製備 18 3. 合環條件最佳化與官能基容忍度測試 24 4. 環化產物結構鑑定 30 5. 反應機制推導 37 6. 結論 39 四、實驗部分 40 1. 分析儀器與基本實驗操作 40 2. 實驗步驟 42 General Procedure 1: Synthesis of III-7a 42 General Procedure 2: Preparation of III-6 44 General Procedure 3: Preparation of III-5 61 General Procedure 4: Preparation of bicyclic γ-lactams III-17 77 五、參考文獻 93 附錄 95 1H、13C與19F NMR光譜 97 X-ray ORTEP 解析圖譜、數據及checkCIF/PLATON report 193

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