臺灣博碩士論文加值系統

本篇論文分為兩個主題。第一部分為香豆素衍生物的有機不對稱 Michael 加成
反應之研究；第二部分為分子內 Wittig 反應，化學選擇合成苯并噻吩與四取代
呋喃化合物。
在第一個主題中，我們成功的使用金雞納一級胺衍生物與酮類，在香豆素
衍生物上建構出光學中心，產物產率最高可達 98%，非鏡像異構物比可達 >20:1，
鏡像超越值可以達到 98%。而之前的有機催化文獻探討中，大多以4-羥基的香
豆素對 α,β 不飽和的官能基進行 Michael 加成反應，而我們的研究卻是以香豆
素衍生物做為受體，與酮類進行 Michael 加成，足以看出特別之處。
在第二個主題中，苯并噻吩衍生物在有機合成中為一重要的研究領域，運
用本實驗室過去合成呋喃的核心概念以有效合成苯并噻吩分子。反應機構推測為
三丁基膦先與醛類或 Michael 受體進行 1,4-加成反應，接著進行氧-醯化和去質
子化，最後經由分子內 Wittig 合環反應，即可獲得苯并噻吩與呋喃產物，產率
介於70-94 %。Ylide 中間體分子上具有酯基與硫酯基，不同的起始物可控制反
應的化學選擇性，而可生成苯并呋喃或呋喃分子。

The dissertation is divided into two parts : investigation of asymmetric
organocatalytic michael additions of ketones toward coumarin derivatives (part I),
and preparation of Functional Benzothiophene and Furan via Intramolecular Wittig
Reactions (part II).
In the first part, we showed that asymmetric synthesis of optically active
chroman-2-one derivatives can be achieved starting from ketones and diversely
substituted 3-aroyl coumarins catalysed by readily available cinchona-alkaloid
derived primary amines. A series of substituted chroman-2-one compounds were
obtained in up to 98% ee, up to > 20:1 diastereomeric ratio and 98% isolated yield.
Literature survey reveals that iminium or H-bond catalyzed Michael reaction of
4-hydroxycoumarin to α,β-unsaturated carbonyls has been widely investigated, but
preparation of chroman-2-one derivatives via Michael addition of ketones to 3-aroyl
coumarins has not been reported. Therefore, our unprecedented approach for the
synthesis of optically active coumarin derivatives has a broad synthetic scope and
should be of general interest to preparative chemists and the synthetic organic
community.
The second, benzothiophenes were of great importance in organic chemistry. In
this part, they can be efficiently synthesized according to our developed protocol. The
reaction mechanism is proposed to undergo the 1,4-addition reaction of PBu3 toward
Michael acceptors followed by acylation, deprotonation and finally intramolecular
Wittig reactions to furnish benzothiophenes or furans in 70-94% yields. Furthermore,
the phosphorus ylide with ester and thioester groups could undergo chemoselective
intramolecular Wittig reactions to provide the corresponding furans or
benzothiophene.

目錄
簡歷 I
摘要 II
謝誌 IV
第一章 酮類與香豆素衍生物的有機不對稱 Michael 加成反應之研究
1-1. 前言 .................................................................................................................................... 1
1-1-1. 不對稱的背景 ......................................................................................................... 1
1-1-2. 香豆素的介紹 ......................................................................................................... 3
1-1-3. 金屬催化文獻探討 ................................................................................................. 4
1-1-4. 有機催化文獻探討 ................................................................................................. 5
1-1-5. 掌性催化劑的介紹 ............................................................................................... 10
1-2. 研究動機 ........................................................................................................................ 17
1-3. 實驗結果與討論 ............................................................................................................ 19
1-3-1. 反應最佳化 ........................................................................................................... 19
1-3-2. 香豆素環上的官能基的變化與此Michael 加成反應的變化 ............................ 28
1-3-3. 香豆素環外的官能基的變化與此Michael 加成反應的變化 ............................ 29
1-3-4. 改變反應式中的親核試劑對於此Michael 反應的變化 .................................... 31
1-4. 連續一鍋化反應Sequential one-pot synthesis ........................................................... 34
1-5. 可能的反應機構之過度態及絕對立體組態 ................................................................ 35
1-6. 結論 ................................................................................................................................ 39
1-7. 實驗部分 .......................................................................................................................... 40
1-7-1. 分析儀器及基本實驗操作 ................................................................................... 40
1-7-2. 基本實驗操作 ......................................................................................................... 41
1-7-3. 光譜數據 ............................................................................................................... 41
1-7-4. 文獻 ....................................................................................................................... 56
第二章 分子內 Wittig 反應，化學選擇合成苯并噻吩與四取代呋喃化合物
2-1. 前言 .................................................................................................................................. 59
2-2. 苯并噻吩的合成策略及文獻 .......................................................................................... 60
2-2-1. 過渡金屬催化合成法 ............................................................................................. 60
2-2-2. 芳炔金屬化加上親電子的硫官能基 ..................................................................... 61
2-2-3. 芳香族親核取代反應 (SNAr) ................................................................................ 61
2-2-4. 鄰位鋰化環化反應 ................................................................................................. 62
2-3 研究動機 ............................................................................................................................ 64
2-4. 實驗結果與討論 ............................................................................................................ 67
2-4-1. α,β 不飽和的查爾酮 (chalcone) 起始物 91 的合成.......................................... 67
2-4-1-1. 起始物 91 與醯氯反應 .................................................................................. 68
2-4-1-2. 最佳化試劑當量條件 ...................................................................................... 68
2-4-1-3. 最佳化試液與試液量 ...................................................................................... 69
2-4-1-4. 起始物 91 與醯氯反應之探討 ...................................................................... 69
2-4-1-5. 反應機構之探討 ...................................................................................... 72
2-4-2. 不同官能基起始物 99 之反應探討 ..................................................................... 74
2-4-2-1. 起始物 99 與醯氯反應之探討 ...................................................................... 75
2-4-2-2. 起始物 99 與醯氯反應機構探討 ............................................................ 78
2-4-3. 起始物上不同官能基之化學選擇性探討 ............................................................. 82
2-5. 結論 ................................................................................................................................ 83
2-6. 實驗部分 .......................................................................................................................... 84
2-6-1. 分析儀器及基本實驗操作 ................................................................................... 84
2-6-2. 基本實驗操作 ......................................................................................................... 85
2-6-3. 光譜數據 ............................................................................................................... 86
2-6-4. 文獻 ....................................................................................................................... 94
VIII
附錄一 1H-NMR、13C-NMR 之光譜圖............................................................................... 97
附錄二 X-ray 單晶繞射結構解析與數據 ........................................................................... 167
附錄三 文獻發表 .................................................................................................................. 246

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