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研究生:楊孔碩
研究生(外文):Kung-Shuo Yang
論文名稱:設計開發主架構為樟腦的新型對掌輔助劑,對掌螯合劑,並探討其在不對稱有機合成上的應用
論文名稱(外文):Design and Synthesis of Novel Camphor Derived Chiral Auxiliary/Ligands and Their Synthetic Applications in Organic Reaction
指導教授:陳焜銘陳焜銘引用關係
指導教授(外文):Kwunmin Chen
學位類別:博士
校院名稱:國立臺灣師範大學
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:2002
畢業學年度:90
語文別:中文
論文頁數:380
中文關鍵詞:對掌輔助劑對掌螯合劑
外文關鍵詞:chiral auxiliarychiral ligand
相關次數:
  • 被引用被引用:2
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中文摘要
本論文旨在設計開發主架構為樟腦的新型對掌輔助劑、對掌螯合劑,並探討其在不對稱有機合成上的應用,論文主要分為五個部分。
第一個部分研究重點在於設計與合成出新型的對掌輔助劑,並探討其所衍生之對掌a,b不飽和烯類與睛氧類偶極化合物之[3+2]合環反應,生成具有高非鏡像選擇性之對掌五圓雜環產物(>90% de),並且成功的經由還原反應,高效率地回收立體輔助劑。
第二個部分利用合成出的對掌輔助劑進行Baylis-Hillman反應,以對掌輔助劑衍生物為起始物,在三級胺的催化作用下與醛類進行加成反應,生成具有a-methylene-b-hydroxyl結構的產物。應用一系列的醛類作為反應物並且實驗過程中發現在DMSO與THF/H2O兩種不同的溶劑系統中,不但有著高非鏡像超越值(94-98% de),並且有著完全相反的立體反應中心。
第三個部分乃設計合成以樟腦為主要架構的對掌螯合劑,並且搭配鑭系元素路易士酸來探討Baylis-Hillman之鏡像選擇性反應,實驗的重點在提高其鏡像超越值並改善Baylis-Hillman的反應速率。嘗試多種壓克力酯為起始物,並且成功的應用1-奈基壓克力酯為反應物,在新型立體催化劑作用之下,有著相當良好的反應速率(反應時間二十分鐘)與鏡像超越值(70-95% ee),。
第四個部份為應用新型對掌輔助劑,進一步合成多種不對稱a,b不飽和烯類, 在四價醋酸鉛的氧化作用下,與N-aminophthalimide進行分子間合環反應,生成三環氮丙啶(aziridine)。本反應在以二氯甲烷為溶劑,室溫下快速反應生成高產率的產物(86-95%),並且有著極佳的非鏡像超越值(>90% de)。
第五個部分乃利用設計合成的對掌螯合劑,搭配四價醋酸鉛,製備對掌四價醋酸鉛試劑,在二氯甲烷溶劑中與一系列非對掌稱性之烯類進行反應,生成高產率並且具有高鏡像選擇性的氮丙啶(67-95% ee)
ABSTRACT
Design and Synthesis of Novel Camphor Derived Chiral Auxiliary/Ligands and Their Synthetic Applications in Organic Reaction
Thesis is divided into five sections, they are as follows:
Section 1: A novel camphor derived chiral auxiliary was designed and synthesized. Starting with (1R)-ketopinic acid, the chiral camphor pyrazolidinon was prepared in three steps with 91 % overall yield. At the first stage, the chiral auxiliary was used to study [3+2] cyclization with various nitril oxides to form five membered rings. Results were in good yield and diasteroselectivities. Using reduction cleavage was successfully recovered the chiral auxiliary.
Section 2: Tried Baylis-Hillman reaction to construct a-methylene-b-hydroxyl functionality by using the chiral auxiliary derived acrylate as a reactant. On treatment with various aldehydes in presence of DABCO obtained reasonable good chemical yield (68-92%) and excellent diastereoselectivity (94-98%). To our surprise, different solvent system DMSO and THF/H2O showed opposite absolute stereochemistry.
Section 3: Design and synthesis of novel camphor derived chiral ligands possessing carboxylic acid functionalities were applied on enantiomeric Baylis-Hillman reaction. By using a-napthyl acrylate as a reactant we improved greatly the reactivity by completing the reaction in 20 minutes. At the same time, used the catalytic amount chiral ligand maching lanthanide (3 mol%) to catalyze Baylis-Hillman reactions by treating with various aldehydes obtained reasonable to high enantioselectivities (70-95%) was unprecedented.
Section 4: The chiral auxiliary derivaties a,b-unsaturated olefins are used to do aziridination with N-aminophthalimide in the presence of lead tetracetate to form three membered ring aziridines. Reactions were carried on in dichloromethane at room temperature for 10 minutes and obtained good chemical yield (86-95%) and good diastereoselectivity (>90% de). In this also the chiral auxiliary had recovered successfully by solvolysis with methanol in the presence of catalytic amount of DMAP.
Section 5: The novel chiral ligands were complexed with lead tetraacetate treated with various achiral olefins in the presence of an equal equivalent of N-aminophthalimide to obtain the corresponding aziridines with high enantioselectivities. Reactions were carried out in dichloromethane at 0o C and obtained good chemical yield and reasonable good enantioselectivity (67-95%). We had determined absolute chemistry by changing the original template to the chiral auxiliary when compared with the previous experiments.
目錄
謝誌
中文摘要
英文摘要
一、以樟腦架構為主的新穎對掌輔助劑之設計與合成……………….1
二、對掌輔助劑在[3+2]合環反應上的應用……………………………4
實驗步驟及光譜數據……………………………………………..9
三、非對稱Baylis-Hillman反應…………………………………….…19
3-1、非鏡像選擇性之Baylis-Hillman反應……………………..20
實驗步驟及光譜數據…………………………………….32
3-2、Baylis-Hillman反應性之研究………………………………38
實驗步驟及光譜數據……………………………...……….52
3-3、鏡像選擇性之Baylis-Hillman反應……………………..….58
實驗步驟及光譜數據………………………………….…78
四、非對稱氮丙啶之合成………………………………………………98
4-1、非鏡像選擇性反應合成氮丙啶……………………..……….98
實驗步驟及光譜數據……………………………………114
4-2、鏡像選擇性反應合成氮丙啶………………………………124
實驗步驟及光譜數據…………………………………….134
參考資料……………………………………………………………..141
1H-NMR、13C-NMR圖譜及X-ray單晶繞射結構解析圖………145
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