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研究生:孫崇喜
研究生(外文):Chong-si Sun
論文名稱:利用鈀催化還原異構與烯醇丙烯化反應不對稱合成4-及5-取代哌啶甲酸衍生物
論文名稱(外文):Asymmetric Synthesis of 4- or 5-Oxopipecolic Acid Derivatives via Palladium-Catalyzed Formate Reduction and Enolate Allylation.
指導教授:侯敦仁
學位類別:碩士
校院名稱:國立中央大學
系所名稱:化學研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:208
中文關鍵詞:環閉合置換鈀催化甲酸還原酮基哌啶甲酸
外文關鍵詞:Oxopipecolic acidRing closing metathesisPalladium-catalyzed formate reduction
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本論文提供「環閉合置換反應(ring closing metathesis, RCM)後產生之烯烴進行選擇性衍生化的方法」,並藉由鈀金屬催化甲酸還原反應(palladium catalyzed formate reduction)來達成此一目的。我們使用二氫吡喃(dihydropyrane)雜環 4 為模型,以改變甲酸還原反應之配位基的方式,尋找適用於環閉合置換後的含氧六員雜環進行甲基烯衍生之最佳條件。
為了探討此方法於有機合成上的實用性,我們更進一步地合成了4-及5-取代哌啶甲酸(pipecolic acid)的前驅物 28a、29、35、36 及 38。其關鍵步驟在於「環閉合置換反應來組成哌啶甲酸六員雜環的基本骨架,並串聯鈀金屬催化甲酸還原反應進行甲基烯衍生」;而哌啶甲酸2 號位置上的掌性中心,則藉由 Dellaria 教授的「光學輔助胺基乙酸烯醇合成子之立體選擇烷化反應stereoselective alkylation)」及 Royer、Husson 團隊的「去質子/光學輔助立體選擇質子化反應」進行不對稱合成的控制。
The method for regioselective palladium-catalyzed formate reduction of allylic benzoate formed by ring closing metathesis was developed. We used 2,2-diphenyl-tetrahydro-2H- pyrane 4 as the model compound, and found an optimized condition of formate reduction by screening several ligands.
4- or 5-Substituted pipecolic acid precursors 28a, 29, 35, 36 and 38, which are biologically active compounds or their precursors, were synthesized by this method. The key steps of these syntheses involve the formation of the skeleton of pipecolic acids with ring closing metathesis and transformation of endo-olefins with palladium-catalyzed formate reduction. We used stereoselective alkylation and deprotonation/stereoselective protonation to
control the generation of chiral center in these pipecolic acid precursors.
中文摘要 ......................................................................................................................... I
Abstract ......................................................................................................................... II
誌謝 ........................................................................................................................ III
總目錄 ...................................................................................................................... IV
圖目錄 ...................................................................................................................... VI
表目錄 .................................................................................................................... VIII
附圖目錄 ...................................................................................................................... IX
縮寫表 ..................................................................................................................... XIII
第一章 序論: ............................................................................................................. 1
1-1 研究動機: .................................................................................................. 2
1-2 烯烴置換反應與環閉合置換反應的介紹: .............................................. 2
1-3 環閉合置換後進行衍生化的實例: .......................................................... 6
1-4 鈀金屬催化甲酸還原反應的介紹: .......................................................... 9
第二章 鈀金屬催化甲酸還原反應應用於環化化合物的研究與討論: ............... 13
2-1 起始物 1 的製備: .................................................................................. 14
2-2 起始物 2 的製備: .................................................................................. 16
2-3 RCM 前驅物-化合物 3 的合成: ........................................................... 17
2-4 環閉合置換及鈀金屬催化甲酸還原反應的條件: ................................ 18
2-5 環內烯烴化合物 5b 結構的確定: ........................................................ 23
第三章 串聯環閉合置換與鈀金屬催化甲酸還原反應之結論: ........................... 25
第四章 合成上的應用: ........................................................................................... 27
4-1 合成分子的選定: .................................................................................... 27
4-2 光學輔助胺基乙酸烯醇合成子進行立體選擇烷化反應的介紹: ........ 32
4-3 Royer 與 Husson 團隊的去質子卅光學輔助立體選擇質子化反應之介紹: ............................................................................................................. 34
4-4 4 號碳位置上具有官能基取代之哌啶甲酸合成方法: ......................... 35
4-5 5-酮基取代哌啶甲酸合成方法: ............................................................. 38
4-6 同時合成 4, 5-酮基取代哌啶甲酸的方法: ........................................... 39
第五章 4-, 5-酮基取代哌啶甲酸合成之研究與討論: .......................................... 43
5-1 光學輔助化合物 16 之製備: ................................................................ 44
5-2 光學輔助化合物 16 進行立體選擇烷化反應及N-上烷化反應,來形成雙烯化合物: ............................................................................................. 45
5-3 5-酮基取代哌啶甲酸新合成路徑之構思: ............................................. 48
5-4 D-丙烯基丙氨酸甲酯 22 的形成及RCM 前驅物-雙烯化合物 23 的製備: ......................................................................................................... 49
5-5 環閉合置換合成哌啶甲酸之骨架 24: .................................................. 50
5-6 鈀金屬催化甲酸還原反應及5-酮基取代哌啶甲酸衍生物的合成: .... 51
5-7 RCM 前驅物-雙烯化合物 32 的製備: .............................................. 54
5-8 各式(R)-4-取代哌啶甲酸衍生物的合成: .............................................. 57
5-9 (S)- 4-取代哌啶甲酸衍生物的合成: ...................................................... 59
第六章 總結: ........................................................................................................... 63
第七章 實驗步驟: ................................................................................................... 65
7-1 溶媒及處理過程: .................................................................................... 65
7-2 實驗器材及光譜儀器: ............................................................................ 65
7-3 實驗步驟: ................................................................................................ 69
第八章 參考資料: ................................................................................................... 99
第九章 附圖目錄: ................................................................................................. 105
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