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Author: 劉軒如
Liu, Syuan-Ru
Thesis Title: 一、對掌樟腦架構衍生之α-重氮羰基輔助劑於不對N-H鍵嵌入反應之探討 二、有機催化Michael加成反應在製備掌性四級碳化合物之探討
1.The Studies of N-Phenyl Camphorpyrazolidinone Derived a-Diazocarbonyl in Diastereoselective N-H Insertion Reaction 2. Asymmetric Organocatalytic Michael Reaction for the Synthesis of Quaternary Carbon-Containing Compounds
Advisor: 陳焜銘
Chen, Kwun-Min
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2010
Academic Year: 98
Language: 中文
Keywords (in Chinese): 不對稱合成重氮
Keywords (in English): diazo
Thesis Type: Academic thesis/ dissertation
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  • 本論文共分兩大部分:第一部分探討非鏡像選擇性之胺化反應,第二部分則探討鏡像1,4-加成反應。第一部分以本實驗室合成之對掌輔助劑110進行修飾,製備α-重氮羰基對掌輔助劑起始物123,在室溫下,以二氯甲烷為作為反應溶劑,與各種胺類受質124及5 mol%之二價銠金屬催化劑進行不對稱N-H鍵嵌入反應,可得到最佳產率(65%)及非鏡像選擇性(88:12),產物分子經由核磁共振光譜分析及X光單晶繞射確定新建構之立體中心構形為R。另外,可成功將對掌輔助劑110切除回收,得到98%之對掌輔助劑及80%的胺基醇化合物131e。
    第二部分利用本實驗室所開發之含有樟腦分子架構之L-脯胺酸有機催化劑230催化β-硝基苯乙烯類起始物136、147及α,α-不同取代之醛類起始物198、228進行不對稱Michael加成反應,篩選出以-硝基苯乙烯136及4當量的2-苯基丙醛228為起始物,在室溫下,以甲醇為反應溶劑,以20 mol%的催化劑進行反應時,得到最佳之產率(62%)、非鏡像選擇性(88:12)及鏡像超越值(52%)。

    This dissertation was divided into two parts, they are as follows: The first part represents to study the chiral auxiliary mediated diastereoselective N-H insertion by using the modified derivative from N-phenyl camphorpyrazolindione (110). The reaction was carried out in CH2Cl2 at ambient temperature, by using the α-diazocarbonyl compound (123) as the starting material and catalytic amount of rhodium acetate (5 mol%) generate metallocarbene intermediate. This was followed by addition of amine source (124). In this process N-H insertion products were obtained in high yield up to 65% yield and with up to 88:12 diastereoselectivity. The newly generated chiral center of the major product shows R configuration was confirmed by H-NMR studies and X-ray crystallographic data. On the other hand, the chiral auxiliary was successfully removed, and the recovered yield of 110 up to 98% and amino alcohol 131e was obtained in 80% yield.
      In the second part, the Michael additoion ofα,α-disubstituted aldehydes (198, 228) to β-nitroalkenes (136, 147) have been developed. The Michael addition is efficiently catalyzed by the pyrrolidin-camphor derivative (230) as bifunctional organocatalyst producing Michael adduct in moderate to good yield and stereoselectivities. The reaction was carried out in MeOH under room temperature by using β-nitrostyrene and 4 equivalents of donor aldehyde as starting material and 20 mol% of catalyst 230. The Michael adduct achieved with best result is 62% yield with 88:12 diastereoselectivity and 52% enantioselectivity.

    第一章 對掌樟腦架構衍生之α-重氮羰基輔助劑於不對稱N-H鍵嵌入反應之探討 1-1 導論 1 1-1-1 前言 1 1-1-2 重氮化合物進行反應之影響因素 2 1-1-2-1 過渡金屬及配位基對重氮化合物分解反應的影響 3 1-1-2-2 重氮羰基化合物上兩端取代基對反應性的影響 8 1-1-3 重氮羰基化合物之反應類型 10 1-1-4 不對稱N-H鍵嵌入反應之文獻探討 15 1-1-5 對掌輔助劑於不對稱X-H嵌入反應上之應用 20 1-1-6 研究動機 21 1-2 實驗結果與討論 22 1-2-1 對掌輔助劑的設計與製備 22 1-2-2 利用α-重氮羰基對掌輔助劑進行不對稱N-H嵌入反應 24 1-2-2-1 金屬催化劑的篩選 24 1-2-2-2 催化劑當量數之探討 27 1-2-2-3 溶劑效應 28 1-2-2-4 溫度效應 30 1-2-2-5 反應步驟之影響 32 1-2-2-6 取代基效應 33 1-2-3 反應機構探討 36 1-2-4 對掌輔助劑之回收 36 1-2-5 結論 38 1-3 實驗步驟及數據 39 1-3-1 分析儀器及基本實驗操作 39 1-3-2 對掌輔助劑的製備 41 1-3-3 對掌α-酮醯胺衍生物的製備 42 1-3-4 對掌輔助劑回收 48 第二章 有機催化Michael加成反應在製備掌性四級碳化合物之探討 2-1 導論 50 2-1-1 前言 50 2-1-2 有機催化劑催化Michael加成反應之探討 52 2-1-2-1 非共價催化 52 2-1-2-2 共價催化 57 2-1-2-3 雙官能基催化劑 63 2-1-3 Michael加成反應之應用 66 2-1-4 研究動機 68 2-2 實驗結果與討論 69 2-2-1 有機催化劑的合成概念 69 2-2-2 有機催化劑應用於不對稱Michael加成反應之探討 70 2-2-2-1 溶劑效應 70 2-2-2-2 催化劑篩選 72 2-2-2-3 添加劑效應 76 2-2-2-4 催化劑當量數之探討 82 2-2-2-5 2-苯基丙醛當量數之探討 83 2-2-2-6 取代基效應 84 1-2-3 反應機構探討 87 1-2-4 結論 88 2-3 實驗步驟及數據 89 2-3-1 分析儀器及基本實驗操作 89 2-3-2 一般實驗步驟及光譜數據 91 參考文獻 102 附錄一、1H-NMR、13C-NMR之光譜 108 附錄二、X-ray單晶繞射結構解析與數據 155

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