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Author: 簡崇瀚
Thesis Title: 多取代環己烷化合物之有機催化連鎖環化反應
Organocatalytic Synthesis of Functionalized Cyclohexanes via Domino Michael/Michael/Cyclization Reaction
Advisor: 陳焜銘
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2013
Academic Year: 101
Language: 中文
Number of pages: 134
Keywords (in Chinese): 一鍋化不對稱有機催化連鎖反應多取代二螺環己烷
Keywords (in English): domino/cascade, dispirocyclohexanes, Michael/Michael/cyclization
Thesis Type: Academic thesis/ dissertation
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  • 藉由二分子一鍋化反應,進行不對稱有機催化連鎖反應,發展鏡像選擇性全取代二螺環己烷。本實驗使用2-芳香環亞甲基氫茚-1‚3-二酮和醛類,加入5 mol%的‚-L-雙苯環脯胺醇矽醚有機催化劑及 20 mol%的1‚4-二氮雜二環[2.2.2]辛烷,在二甲基二醯胺為溶劑及-20 oC下,進行Michael/Michael/aldol連鎖反應,得到全取代二螺環己烷,其有不錯的產率及非常好的立體選擇性(>95:5 dr 和 高達 99% ee);除此之外,經由單晶繞射X-ray確認其產物絕對立體組態;另一方面,本實驗也嘗試使用2-(4-硝基苯亞甲基)-氫茚-1‚3-二酮及丙烯醛,以20 mol%的掌性三級胺進行催化,在二甲基二醯胺為溶劑及0 oC下,經由Michael/Michael/cyclization連鎖反應,可得到五取代二螺環己烷,其產率及鏡像選擇性在持續探討中。本實驗成功利用二種不同策略,進行合成多取代環己烷,並且建構兩個四級碳中心,在未來合成發展上極具經濟效益。

    An interesting asymmetric organocatalytic domino reaction by using two components have been developed that gives fully substituted dispirocyclohexanes in one pot. In this study‚ treatment of 2-arylideneindane-1‚3-diones with aldehydes using a catalytic amount of ‚-L-diphenylprolinol silyl ether (5 mol%) and DABCO (20 mol%) in DMF at -20 oC to give fully substituted dispirocyclohexanes via domino Michael/Michael/aldol process with moderate chemical yields and high-to-excellent stereoselectivities (>95:5 dr and up to 99% ee). Besides‚ the absolute stereochemistry is determined by single crystal X-ray analysis of product. On the other hand‚ in another study‚ reaction was carried out under 0 oC by using the (2-(4-nitro-benzylidene)-indan-1‚3-dione) and acrolein as starting materials in DMF in the presense of chiral tertiary amine catalyst (20 mol%) to give pentasubstituted dispirocyclohexanes via cascade Michael/Michael/cyclization process but the chemical yields and enantioselectivity has not been optimized. Successfully synthesis of multisubstituted cyclohexanes and construct two all-carbon quaternary by using two diferrent strategy are more commercial for another synthetic development in the future.

    第一章 序論 1-1 前言   1 1-2 有機催化劑的發展   2 1-3 有機不對稱胺催化反應  6 1-4 六員環之簡介  9 1-5 六員環之合成途徑  10 1-5-1 以Diels-Alder反應進行環己烯之合成  10 1-5-2 有機不對稱連鎖反應的介紹  12 1-5-3 以Michael-aldol反應合成環己酮分子  14 1-5-4 以不對稱連鎖反應合成多取代環己烷架構  16 1-5-5 螺環吲哚酮於不對稱連鎖合成六員環之應用  19 1-6 研究動機  21 第二章 實驗結果與討論 2-1  不對稱有機催化連鎖反應  22 2-1-1 溶劑效應  23 2-1-2 添加劑和反應條件最佳化之探討  25 2-1-3 取代基效應  27 2-1-4 多取代二螺環己烷之產物結構分析  29 2-1-5 反應機構之探討  30 2-2  掌性三級胺催化不對稱連鎖反應  31 2-2-1 不同催化劑之探討  32 2-1-7 溶劑效應  33 2-1-8 反應機構之探討  35 2-3  結論  36   第三章 實驗部分 3-1 分析儀器及基本實驗操作  37 3-2 連鎖反應合成多取代環己烷之一般步驟  39 3-3 光譜數據  40 3-4 連鎖Michael/ Michael/環化反應之一般步驟及光譜數據  55 第四章 參考文獻 57 附錄一 1H -NMR、13C- NMR光譜圖  59 附錄二 X-ray結構解析與數據  92 附錄三 論文發表期刊  134

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