銅(I)催化碳-硫偶合反應之中間產物和反應機制研究

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研究生：	黃唯愷 Huang, Wei-Kai
論文名稱：	銅(I)催化碳-硫偶合反應之中間產物和反應機制研究 Intermediates and mechanism in the copper-catalyzed C-S cross coupling reaction
指導教授：	徐新光 Shyu, Shin-Guang 韓建中 Han, Chien-Chung
口試委員:	蔡易州 Tsai, Yi-Chou 陳建添 Chen, Chien-Tien 許益瑞 Hsu, I.-Jui
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：	2018
畢業學年度：	106
語文別：	中文
論文頁數：	135
中文關鍵詞：	銅催化、碳-硫偶合反應、銅(I)含氮雜環碳烯錯合物、反應機制、理論計算、二維核磁共振儀
外文關鍵詞：	copper-catalyzed, C-S cross coupling reaction, Cu(I)N-heterocyclic carbene complex, reaction mechanism, DFT calculation, 2D NMR DOSY
相關次數：	點閱：3 下載：0
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本篇論文主要是探討在銅(I)催化碳-硫偶合反應的反應機制和反應中的中間產物。因在之前的實驗當中發現當反應中有配位基1,10- phenanthroline (phen)時能有效地提升碳-硫偶合反應的產率，但在利用ESI-MS探討反應中間產物時卻只看到[Cu(SR)2]-而並沒有看到phen配位在銅上的phen-Cu-SR intermediate，於是想要藉由此篇論文來了解其反應機制究竟為何。
我們認為phen和銅之間為一弱配位鍵，在反應過程中phen可能會從銅上脫離。於是我們就拿一個和過渡金屬間有強共價鍵的含氮雜環碳烯作為反應中的配位基來做為基礎探討其反應機制。透過反應動力學、自由基抑制劑實驗以及理論計算所得到的結果，我們可以得到以含氮雜環碳烯銅錯合物作為催化劑時反應的中間產物為L-Cu-SR (L = IMes, IPr)，且反應路徑為非自由基的氧化加成-還原脫去路徑。
因想要了解以CuI為催化劑時，在非極性和極性溶劑中碳-硫偶合反應的intermediate和配位基phen所扮演的角色，所以我們利用2D NMR DOSY實驗來作探討。從非極性溶劑DOSY圖譜中可以得到[Cu(SR)2]K intermediate以及單獨phen的訊號；另外，從1H NMR實驗結果得知phen可以增加KSR和KOtBu在非極性溶劑的溶解度，其也是提升非極性反應系統產率的主要原因。而在極性溶劑反應系統中，在DOSY圖譜中可以得到[Cu(SR)2]-中間產物，而phen則會和KI生成phen-KI溶於CD3CN中。不論是在極性還是非極性溶劑中反應，反應中間產物皆為銅接兩個SR-的形式來進行反應，且phen不會配位在銅上。透過自由基抑制劑實驗和理論計算的結果可以得知極性和非極性溶劑反應系統皆走兩個電子的氧化加成和還原脫去的反應路徑。

In the thesis, the copper(I) catalyzed C-S crossing coupling reaction mechanism and the reaction intermediate were be discussed. Base on previous experiments of our lab, the 1,10-phenanthroline (phen) increase C-S coupling reactions yield significantly. The phen-Cu-SR species can not be detected by ESI-MS, but [Cu(SR)2]- can. It seems the ligand did not involve the catalytic cycle.
We thought the phen can dissociate from the copper center in the reaction because it does not coordinate with the copper firmly. N-heterocyclic carbene has a strong electron donating and ligand dissociation can be avoided, so we chose it as catalysis to discuss the reaction mechanism. The DFT calculation, kinetic and radical scavenger experiments indicated that L-Cu-SAr (L = IMes or IPr) serves as the dominant intermediate in the catalytic cycle and the reaction is the non-free radical path (OA/RE).
To understand the intermediate and reaction mechanism of CuI catalyzed C-S cross-coupling reaction in the non-polar and polar solvent. We used the 1H DOSY NMR and DFT calculation to study. We found the major intermediate is [Cu(SR)2]-K and free phen in the non-polar solvent reaction by DOSY experiment. Besides, phen can enhance the solubility of KOtBu or KSR in the non-polar solvent reaction. On the other hand, the DOSY spectrum showed that [Cu(SR)2]- is the dominant intermediate in the polar solvent and phen coordinate potassium iodide to produce phen-KI dissolving the CD3CN. Regardless of solvent polarity, the phen in the reaction is not coordinated to CuSR to form phen-Cu-SR. The DFT calculation and radical scavenger experiments indicated that the CuI catalyzed C-S crossing coupling reaction path are the non-free radical path (OA/RE) in the non-polar and polar solvent.

摘要    I
Abstract    II
誌謝    III
圖目錄    VII
表目錄    X
第一章 緒論    1
1-1 前言    1
1-2 碳-硫鍵偶合反應之背景及簡介    1
1-2-1以鈀(Pd)金屬作為催化劑的碳-硫偶合反應    2
1-2-2以鎳(Ni)金屬作為催化劑的碳-硫偶合反應    6
1-2-3以銅(Cu)金屬作為催化劑的碳-硫偶合反應    10
(一) 銅催化反應之系統    10
(二) 銅催化反應之碳-硫偶合反應    11
(三) 銅催化碳-硫偶合反應之反應機制    15
1-3 卡賓 (carbene)和含氮雜環碳烯錯合物 (N-heterocyclic carbene complexes)的簡介和合成    18
1-4 研究方向    22
第二章 實驗部分    23
2-1 實驗藥品    23
2-1-1溶劑    23
2-1-2 藥品    23
2-1-3 氣體    25
2-2 實驗儀器    26
2-2-1 手套箱 (Dry box)    26
2-2-2 氣相層析儀 (Gas chromatography)    26
2-2-3 氣相層析質譜儀 (Gas chromatography mass spectrometer)    26
2-2-4 核磁共振儀 (Nuclear magnetic resonance)    26
2-2-5 二維核磁共振儀 (Diffusion ordered spectroscopy，DOSY)    27
2-2-6 元素分析儀 (Elemental analyzer)    27
2-3 實驗步驟    27
2-3-1合成(1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) copper(I) chloride (簡稱:IMes-Cu-Cl)35    27
2-3-2合成1,3-Bis(2,6-diisopropyl)imidazol-2-ylidene) copper(I) chloride (簡稱: IPr-Cu-Cl)35    28
2-3-3合成IMes-Cu-SPh36    29
2-3-4 以CuI為催化劑進行碳-硫偶合反應    30
2-3-5 以各種不同的含氮雜環碳烯為催化劑進行碳-硫偶合反應    30
2-3-6 以IMes-Cu-Cl為催化劑搭配各種鹼進行碳-硫偶合反應    31
2-3-7 以IMes-Cu-Cl作為催化劑時在碳-硫偶合反應中加入自由基抑制劑    31
2-3-8 以IMes-Cu-Cl作為催化劑和各種碘苯衍生物進行碳-硫偶合反應    31
2-3-8.1 以iodobenzene為起始物    32
2-3-8.2 以2-iodotoluene為起始物    32
2-3-8.3 以3-iodotoluene為起始物    32
2-3-8.4 以4-iodotoluene為起始物    33
2-3-8.5 以4-iodoanisole為起始物    33
2-3-8.6 以4-iodobenzonitrile為起始物    33
2-3-8.7 以4-iodobenzotrifluoride為起始物    33
2-3-8.8 以1-iodonaphthalene為起始物    34
2-3-9 動力學實驗    34
2-3-10 合成potassium thiophenolate    34
2-3-11 合成potassium 2,6-dimethylthiophenolate    35
2-3-12 合成potassium p-tolythiolate    35
2-3-13 以CuI為催化劑和不同arylthiol衍生物在甲苯中進行碳-硫偶合反應    36
2-3-13.1 反應沒有配位基phen的參與    36
2-3-13.2 反應有配位基phen的參與    36
2-3-14 以CuI為催化劑和不同potassium arylthiolate衍生物在甲苯中進行碳-硫偶合反應    36
2-3-14.1 反應沒有配位基phen的參與    37
2-3-14.2 反應有配位基phen的參與    37
2-3-15 以CuI作為催化劑時在碳-硫偶合反應中加入自由基抑制劑 (溶劑為甲苯)    37
2-3-16 在沒有催化劑 (CuI)的條件下在乙腈中進行碳-硫偶合反應    38
2-3-17 以CuI為催化劑和不同arylthiol衍生物在乙腈中進行碳-硫偶合反應    38
2-3-17.1 反應沒有配位基phen的參與    38
2-3-17.2 反應有配位基phen的參與    38
2-3-17.3 在反應中有配位基phen的情況下加入自由基抑制劑cumene    39
2-3-18 以CuI為催化劑和不同potassium arylthiolate衍生物在乙腈中進行碳-硫偶合反應    39
2-3-18.1 反應沒有配位基phen的參與    39
2-3-18.2 反應有配位基phen的參與    40
2-3-19 1H DOSY NMR的樣品製備    40
2-3-19.1 圖四十一1H DOSY NMR的樣品製備    40
2-3-19.2 圖四十五1H DOSY NMR的樣品製備    40
2-3-19.3 圖四十六1H DOSY NMR的樣品製備    41
2-3-19.4 圖四十七1H DOSY NMR的樣品製備    41
2-3-19.5 圖四十八1H DOSY NMR的樣品製備    41
2-3-20 1H DOSY NMR待測物半徑的計算 (robs)    42
第三章 結果與討論    43
3-1 以NHC-Carbene Complexes為催化劑進行碳-硫偶合反應    43
3-2 在以IMes-Cu-Cl為催化劑所進行的碳-硫偶合反應中加入自由基抑制劑    47
3-3 動力學實驗 (IMes-Cu-Cl/IMes-Cu-SPh)    48
3-4 以各種不同的碘苯衍生物進行銅(I)碳-硫偶合反應    49
3-5含氮雜環碳烯銅錯合物催化碳-硫偶合反應的反應機制探討    50
3-6 在非極性溶劑中的1H DOSY NMR分析    53
3-7 phen在非極性溶劑反應系統中所扮演的角色    56
3-8 phen在C6D6中和KI的關係    59
3-9 在極性溶劑 (乙腈)下進行銅(I)碳-硫偶合反應    61
3-10 在極性溶劑 (CD3CN)下進行1H DOSY 分析    63
3-11 phen在極性溶劑反應系統中所扮演的角色    65
3-12碘化銅(CuI)催化碳-硫偶合反應的反應機制探討    68
第四章 結論    73
第五章 附錄    75
第六章 參考資料    132

                                

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