以α,β-不飽和酮進行環丙烷化反應 - 不對稱合成天然物Brevipolide H之鏡像異構物

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林靖文(Jing-wen Lin) 查詢紙本館藏

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論文名稱

以α,β-不飽和酮進行環丙烷化反應 - 不對稱合成天然物Brevipolide H之鏡像異構物
(Asymmetric synthesis of (-)-brevipolide H through cyclopropanation of the α,β-unsaturated ketone)

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摘要(中)

本篇論文利用C2對稱的雙烯雙醇化合物2作為起始物，經由交叉置換反應、環丙烷化反應、Sharpless不對稱α-羥基化反應和環閉合置換反應合成天然物brevipolide H的鏡像異構物 (ent-1)。其中天然物的中心結構，是以硫ylide對α,β-不飽和酮5進行環丙烷化反應，形成符合天然物之鏡像異構物的立體位向。此立體結構經由X-ray單晶繞射確定。此外，藉由γ醇上保護基的改變 (乙基甲醚和縮丙酮)，可以發展出相反的環丙烷位向；之後再依序與4-甲基肉桂酸進行酯化、與3-丁烯酸進行Mitsunobu反應，建構天然物brevipolide H之鏡像異構物 (ent-1) 右端的4-甲基肉桂酯及左端的5,6-二氫-2-吡喃酮結構。

摘要(英)

We utilized the C2 symmetric diene-diol 2 as the starting material, and the skeleton of ent-brevipolide H (ent-1) was prepared by the sequence of cross metathesis, cyclopropanation, Sharpless asymmetric α-hydroxylation and ring-closing-metathesis. The anti-addition of the sulfur ylide to the α,β-unsaturated enone 5 was be developed to generate the key cyclopropane moiety, whose stereochemistry was lated confirmrd by X-ray crystallography. The substrates with different hydroxyl protecting groups, i.e. ethoxymethyl ether and acetonide, lead to the different stereo-assignment of the cyclopropane. The first total synthesis of ent-brevipolide H (ent-1) was achieved after the linkage of 4-methoxycinnamic acid to an ester, the formation of 5,6-dihydro-2-pyrone and deprotection.

關鍵字(中)

★ 環丙烷
★ 交叉置換反應
★ Sharpless不對稱α-羥基化反應
★ 烯醇矽醚
★ 天然物
★ α,β-不飽和酮

關鍵字(英)

★ cyclopropanation
★ brevipolides
★ Sharpless asymmetric α-hydroxylation
★ cross metathesis
★ cyclopropane
★ α,β-unsaturated enone

論文目次

中文論文摘要............................................................................................. I
Abstract .................................................................................................III
總目錄 ..................................................................................................V
圖目錄 ...............................................................................................VII
流程圖目錄.................................................................................. VIIX
表格目錄........................................................................................ VIIX
方程式目錄........................................................................................X
附圖目錄...................................................................................... XI
第一章緒論.........................................................................................1
一、環丙烷的合成..............................................................................6
1−1 環丙烷化反應 (cyclopropanation) 的介紹 ......................6
1−2 非鏡像選擇性環丙烷化反應的探討.............................. 12
二、不對稱α-羥基化反應............................................................. 45
2−1 Sharpless 不對稱雙羥基化反應 (SAD) 的介紹............ 18
2−2 烯醇醚的不對稱α-羥基化反應的介紹......................... 27
2−3 烯醇的 E/Z 幾何異構物.................................................. 29
三、烯烴置換 (olefin metathesis) 反應......................................... 33
3−1 烯烴置換反應的發展及介紹.......................................... 33VI
3−2 高效能催化劑的介紹...................................................... 37
3−3 交叉置換反應 (cross-metathesis) 的介紹..................... 40
3−4 環閉合置換反應 (ring-closing metathesis) 的介紹...... 42
四、研究目的................................................................................... 44
第二章結果與討論 .......................................................................... 45
一、逆合成分析............................................................................... 45
二、結果與討論............................................................................... 49
2−1 起始物的合成.................................................................. 49
2−2 共軛烯烴 (乙基乙烯酮) 的交叉置換反應................... 49
2−3 環丙烷化反應的非鏡像選擇性之探討.......................... 54
2−4 天然物的合成問題及合成順序的改變.......................... 60
2−5 烯醇矽醚的生成及不對稱α-羥基化反應 .................... 63
2−6 天然物 brevipolide H 的鏡像異構物之合成.................. 70
第三章結論 .................................................................................... 75
第四章實驗部份 ............................................................................ 76
一、實驗藥品與溶劑....................................................................... 76
二、實驗器材與儀器....................................................................... 77
三、實驗步驟與光譜數據............................................................... 79
第五章參考文獻…………………………. ....................................111

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指導教授

侯敦仁(Duen-ren Hou)

審核日期

2014-8-28

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