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研究生： 吳學亮
Hsyueh-Liang Wu
論文名稱： 樟腦衍生物為掌性配位基於不對稱合成之研究
Camphor Derived Chiral Ligands in Asymmetric Catalysis
指導教授： 汪炳鈞
Biing-Jiun Uang
口試委員:
學位類別： 博士
Doctor
系所名稱： 理學院 - 化學系
Department of Chemistry
論文出版年： 2004
畢業學年度： 92
語文別： 中文
論文頁數： 305
中文關鍵詞： 樟腦衍生物 、掌性配位基 、不對稱催化劑 、不對稱氧化 、不對稱加成
外文關鍵詞： Camphor Derivatives, Chiral ligand, Asymmetric catalyst, Asymmetric oxidation, Asymmetric addition
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    • 本論文含三個部分：第一個部分是利用Ketopinic Acid衍生之Hydroxamic Acid為掌性配位基進行烯丙醇的不對稱環氧化反應；第二部分是利用Ketopinic Acid衍生之掌性胺基醇或是由樟腦磺酸製備而得之掌性胺基硫醇為掌性配位基進行不對稱二乙基鋅加成反應；第三部分是以第二部分所發展之掌性胺基硫醇應用在不對稱乙烯基鋅加成反應上。
    一、 不對稱環氧化反應：以7.5 mol % 9e 催化(E)-2,3-Diphenyl-2-propen-1-ol進行反應得到環氧醇有44 % e.e.，組態為（2S, 3S）。而以7.5 mol % 11f 催化進行反應得到環氧醇有46-89 % e.e.，組態為（2R, 3R）。當9或11的氮原子取代基愈大，產物的鏡像選擇性愈差；而氮原子取代基愈小，產物的鏡像選擇性愈好，此現象和文獻上Yamamoto與Bolm報告的結果相反。
    二、 不對稱二乙基鋅加成反應：利用掌性胺基醇17b（10 mol %）催化二乙基鋅加成至苯甲醛，在0℃以正己烷為溶劑的條件下得到產率為93%，80% e.e.的掌性二級醇。而以掌性胺基硫醇37為催化劑催化加成反應的進行，產生的二級醇其產率介於75-95 %，而e.e.值介於95-98 % 之間。另外在nonlinear effect 的研究顯示，以15 mol %、20 % e.e. 之37催化二乙基鋅加成至苯甲醛，得到97 % e.e. 的1-苯基丙醇。
    三、 不對稱乙烯基鋅加成反應：以掌性胺基硫醇37為催化劑催化加成反應的進行，產生的烯丙醇其產率介於75-91 %，而e.e.值介於95-100 % 之間。我們發現當乙烯基鋅為雙取代或取代基愈大時，加成後的產物，依然有很高的鏡像選擇性。

    The application of camphor derived chiral ligands in catalytic asymmetric catalysis are described in this thesis which consists of three parts. The first part describes camphor-based hydroxamic acid catalyzed asymmetric epoxidation of allylic alcohols. The second and third dealt with the asymmetric addition of alkyl and alkenyl-zincs to aldehydes.
    1. Asymmetric epoxidation of allylic alcohols：Epoxidation was carried out in the presence of 7.5 mol % of 9e and the corresponding epoxy alcohol was obtained in 44 % e.e. with a (2S, 3S) configuration. The chiral epoxy alcohols were produced in 46-89% e.e. with a (2R, 3R) configuration when 11f was used. Contrary to both Yamamoto’s and Bolm’s results, we found that decreasing the bulk of the N-substituent led to better selectivity. The steric influence of the bornane C2-substituent on the enantioselectivities of epoxidation was evidenced from the enhancement of the e.e. as the size of the substituent increased.
    2. A new class of camphor-derived □-amino alcohols was prepared from ketopinic acid in two steps. When the addition of Et2Zn to benzaldehyde was conducted in the presence of 10 mol % of 17b, 1-phenylpropanol was obtained in 80 % e.e. New □-amino thiols were prepared from (S)-(+)-Camphorsulfonic acid in few steps. Asymmetric addition of Et2Zn to aldehydes was achieved in excellent selectivity using catalytic amount of 37. Nonlinear effect studies showed that the presence of 15 mol % of 37 (30 % e.e.) was able to give1-phenylpropanol in 97 % e.e. and high yield.
    3. The application of catalytic amount of □-amino thiol 37 in asymmetric addition of alkenylzincs to aldehydes gave the corresponding allylic alcohols in up to > 99 % e.e. which provided a pratical method for the synthesis of chiral (E)-allylic alcohols. Highlights of this reaction are the excellent enantioselectivies observed with the new ligand 37 and aromatic aldehydes as well as the efficiency of the reaction with internal alkyne (3-hexyne) and highly substituted terminal alkyne.

    中文摘要…………………………………………………………………i 英文摘要(abstract)………………………………………………….iii 目錄……………………………………………………………………..v 第一章 緒論…………………………………………………………1 第二章 不對稱環氧化反應................................19 2-1文獻回顧..............................................19 2-2結果與討論…………………………………………………………37 2-3結論…………………………………………………………………53 第三章 不對稱二乙基鋅加成反應............................54 3-1文獻回顧..............................................54. 3-1結果與討論…………………………………………………………62 3-3新掌性配位基的構想與設計………………………………………66 3-4文獻回顧……………………………………………………………67 3-5結果與討論…………………………………………………………74 3-6結論…………………………………………………………………88 第四章 不對稱乙烯基鋅加成反應……………………………………89 4-1文獻回顧……………………………………………………………89 4-2結果與討論…………………………………………………………98 4-3結論……………………………………………………………….107 第五章 實驗部分…………………………………………………….108 5-1一般實驗方法…………………………………………………….108 5-2製備掌性hydroxamic acids 9之實驗步驟…………………….110 5-3製備掌性羧酸12之實驗步驟…………………………………….116 5-4製備掌性hydroxamic acids 11之實驗步驟……………….….121 5-5不對稱環氧化反應……………………………………………...129 5-6製備醯胺化合物16a-f之實驗步驟………………………………138 5-7還原醯胺化合物之實驗步驟…………………………………….145 5-8從樟腦磺酸製備 30之步驟………………………………………152 5-9製備31、32、33之實驗步驟…………………………………….157 5-10製備35-38之實驗步驟………………………………………….162 5-11二乙基鋅加成至醛類的標準步驟……………………………..167 5-12不對稱乙烯基鋅加成反應..............................184 參考文獻……………………………………………………….…...204 附錄一HPLC 分析之原始圖譜……………………………………...213 附錄二 氫核磁共振光譜………………………………….....…..250

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