研究生: |
蔡昊諭 Tsai, Hao-Yu |
---|---|
論文名稱: |
碘催化2-苯乙烯醛與吲哚反應通過親核加成/4π-電環化/異構化序列合成 1H-茚 化合物類衍生物 Iodine-Catalyzed Reactions of 2-Styrylaldehydes With Indoles for the Synthesis of 1H-Indene Derivatives via a Nucleophilic Addition/4π-Electrocyclization/Isomerization Sequence |
指導教授: |
姚清發
Yao, Ching-Fa |
口試委員: |
柳如宗
Liu, Ju-Tsung 林文偉 Lin, Wen-Wei 姚清發 Yao, Ching-Fa |
口試日期: | 2023/07/21 |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2023 |
畢業學年度: | 111 |
語文別: | 中文 |
論文頁數: | 219 |
中文關鍵詞: | 吲哚 、茚 、電環化 、親核加成 、異構化序列 |
英文關鍵詞: | indole, indene, electrocyclization, nucleophilic addition, isomerization sequence |
研究方法: | 實驗設計法 |
DOI URL: | http://doi.org/10.6345/NTNU202301302 |
論文種類: | 學術論文 |
相關次數: | 點閱:81 下載:2 |
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茚是一類重要的分子,它不僅引起有機化學家的興趣,因為大量天然和合成化合物含有其特殊骨架而且皆能表現出生物活性或藥物活性,除此之外茚在材料科學也有了相當大的應用與發展,例如在光伏太陽能電池和新型螢光材料的製備。在過去的幾年裡,化學家已經開發了許多方法來構建這種雙環系統,其中探索最多的兩種是涉及分子內弗里德爾-克來福特反應的陽離子過程,以及過渡金屬在組裝茚框架中起關鍵作用的過程。
而本篇論文研究的方向則是利用路易士酸的催化以及電環化過程,來構築中心骨架的茚結構,並藉由接上保護基來產生單一反式結構的起始物,其中可透過探討不同取代基作為親電子基在合環時對於4π電子對的影響,進而發現可利用熱力學的趨勢,得到較穩定的主產物,甚至衍生出對於不同的吲哚作為親核基的探討, 並利用聚焦式微波合成儀將反應時間控制,因為其穩定的加熱模式,進一步從結果探討對於1-甲基-3-(2-苯基-1H-茚-3-基)-1H-吲哚的高度單一反應性。
Indene is an important type of molecule that not only attracts the interest of organic chemists, as a large number of natural and synthetic compounds contain their unique skeletons and can exhibit biological or pharmaceutical activity. In addition, indene has also made significant applications and developments in materials science, such as in the preparation of photovoltaic solar cells and new fluorescent materials. In the past few years, chemists have already developed many methods to construct such a bicyclic system, of which the two most explored are the cationic processes involving intramolecular Friedel-Crafts reaction, and the process in which transition metals play a key role in assembling the indene framework.
The research direction of this paper is to use the catalysis and electrocyclization process of Lewis acid to construct the indene structure of the central skeleton, and to generate a single trans structure starting material by connecting protective groups. By exploring the influence of different substituents as electrophilic groups on 4 π electron pairs during ring formation, it is found that thermodynamic trends can be utilized to obtain more stable main products, Even exploring different indoles as nucleophilic groups has been derived, and the reaction time has been controlled using a focused microwave synthesizer due to its stable heating mode, further exploring the highly single reactivity of 1-methyl-3- (2-phenyl-1H-inde-3-yl) -1H indole from the results.
(1) James H. Lewis, J. G. S. Nonsteroidal antiinflammatory drugs and leukotriene receptor antagonists. Hepatotoxicity Specific Drug. 2013, 33, 369-401.
(2) Hettstedt, C.; Heuschmann, M.; Karaghiosoff, K. Synthesis and Halogen Bonding in the Crystal Structures of the New 2,3-Diiodo Indenone and 1-Ethoxy-2,3-diiodo Indene. Heteroatom Chemistry. 2016, 27, 75-82.
(3) Iakovenko, R. O.; Kazakova, A. N.; Boyarskaya, I. A.; Gurzhiy, V. V.; Avdontceva, M. S.; Panikorovsky, T. L.; Muzalevskiy, V. M.; Nenajdenko, V. G.; Vasilyev, A. V. Superacid-Promoted Synthesis of CF3-Indenes Using Brominated CF3-Enones. European Journal of Organic Chemistry. 2017, 2017, 5632-5643.
(4) Kotipalli, T.; Hou, D. R. Synthesis of Indenes by a BF(3).OEt(2)-Mediated, One-Pot Reaction of Aryl Homopropargyl Alcohols, Aldehydes, and Arenes. Org. Lett. 2018, 20, 4787-4790.
(5) Niharika, P.; Satyanarayana, G. Lewis Acid Catalyzed Dual Bond Formation: One-Pot Synthesis of Indenes. ChemistrySelect. 2018, 3, 289-293.
(6) Preinfalk, A.; Misale, A.; Maulide, N. A Gold(I)-Catalyzed Domino Coupling of Alcohols with Allenes Enables the Synthesis of Highly Substituted Indenes. Chemistry. 2016, 22, 14471-14474.
(7) Barroso, R.; Paraja, M.; Cabal, M. P.; Valdes, C. Synthesis of 1,1-Disubstituted Indenes and Dihydronaphthalenes through C-C/C-C Bond-Forming Pd-Catalyzed Autotandem Reactions. Org. Lett. 2017, 19, 4086-4089.
(8) Mouysset, D.; Tessonnier, C.; Tintaru, A.; Dumur, F.; Jean, M.; Vanthuyne, N.; Bertrand, M. P.; Siri, D.; Nechab, M. Chiral Fidelity in the Diastereoselective and Enantiospecific Synthesis of Indenes from Axially Chiral Benzylidene Cyclanes. Chemistry. 2017, 23, 8375-8379.
(9) Jana, A.; Misztal, K.; Zak, A.; Grela, K. Synthesis of Selectively Substituted or Deuterated Indenes via Sequential Pd and Ru Catalysis. J. Org. Chem. 2017, 82, 4226-4234.
(10) Kinoshita, H.; Fukumoto, H.; Tohjima, T.; Miura, K. Diisobutylaluminum hydride-promoted cyclization of benzyl and phenylsilyl ethers bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes and benzosiloles. Tetrahedron. Letters. 2016, 57, 3571-3574.
(11) Singha, R.; Ghosh, M.; Das, S.; Das, D.; Ray, J. K. Synthesis of 1,3-dibromo-2-aryl-1H-indenes via NBS mediated unusual bromination of 2-alkynylbenzaldoximes. New Journal of Chemistry. 2016, 40, 7269-7272.
(12) Mao, H.; Kim, D. W.; Shin, H. Y.; Song, C. E.; Yang, J. W. Organocatalytic regiospecific synthesis of 1H-indene-2-carbaldehyde derivatives: suppression of cycloolefin isomerisation by employing sterically demanding catalysts. Org. Biomol. Chem. 2017, 15, 1355-1362.
(13) Bandi, V.; Kavala, V.; Konala, A.; Hsu, C. H.; Villuri, B. K.; Reddy, S. R.; Lin, L.; Kuo, C. W.; Yao, C. F. Synthesis of Polysubstituted Cyclopentene and Cyclopenta[ b]carbazole Analogues from Unsymmetrical 4-Arylidene-3,6-diarylhex-2-en-5-ynal and Indole Derivatives via an Iodine Mediated Electrocyclization Reaction. J. Org. Chem. 2019, 84, 3036-3044.
(14) Gawande, S. D.; Kavala, V.; Zanwar, M. R.; Kuo, C.-W.; Huang, H.-N.; He, C.-H.; Kuo, T.-S.; Yao, C.-F. Molecular Iodine-Mediated Cascade Reaction of 2-Alkynylbenzaldehyde and Indole: An Easy Access to Tetracyclic Indoloazulene Derivatives. Advanced. Synthesis & Catalysis. 2013, 355, 3022-3036.
(15) Yasumoto, M.; Ueki, H.; Soloshonok, V. A. Thermal 1,3-proton shift reaction and its application for operationally convenient and improved synthesis of α-(trifluoromethyl)benzylamine. Journal of Fluorine Chemistry. 2007, 128, 736-739.
(16) Ma, X.; Xu, Q.; Li, H.; Su, C.; Yu, L.; Zhang, X.; Cao, H.; Han, L.-B. Alcohol-based Michaelis–Arbuzov reaction: an efficient and environmentally-benign method for C–P(O) bond formation. Green Chemistry. 2018, 20 (15), 3408-3413.
(17) Chu, C.-M.; Huang, W.-J.; Liu, J.-T.; Yao, C.-F. Highly efficient iodine-catalyzed hydroarylation of arenes with styrenes. Tetrahedron Letters. 2007, 48, 6881-6885.
(18) Li, D.-Y.; Wang, A.; Zhu, X.-P.; F, W.; Liu, P.-N. Direct access to substitute benzo[b]carbazoles through cascade annulation of 2-vinylbenzaldehydes with indoles. Chem. Commun., 2019, 55, 3339-3342