過渡金屬催化新轉變為高度官能有機骨架的合成

本文描述了利用金、鉑以及銅金屬鹽來開發新型的有機合成方式，利用這些金屬可以針對一般現成的基質進行溫和、具有選擇性以及高效的氧化轉換，進而取得可廣泛應用在合成上的含氮、氧或是硫的複雜有機分子。為了便於作更詳細的說明，本文將分為四個章節。第一章論述了利用一價金與二價鉑來進行可區域控制的催化使1-aryl-3-en-1-ynes產生水和反應，進而選擇性地取得3-en-1-ones 或 2-en-1-ones。在此，我們也發展了一鍋化合成方式，對於酮類產物3-en-1-ones 或 2-en-1-ones直接進行還原，進一步取得烯丙基醇(allylic alcohols)及高烯丙基醇(homoallylic alcohols)，而我們的實驗結果也顯示了催化劑的大小在這裡扮演相當重要的角色。第二章論述了1,6-enynes與苯羥胺(N-hydroxyanilines)透過金催化產生動力學尚不穩定的三取代硝酮，我們利用碳鍊上的烯基可以有效地捕捉這種短暫形成的化合物，進一步行具有立體特異性的環加成反應。值得注意的是，此類的環化牽涉了一個非典型的羥胺基氮對金配位炔基鍵進行攻擊，我們的資料顯示對於多數的炔丙基醚(propargyl ethers)，苯羥胺會以氧進行攻擊，然而對於烯炔丙基醚(allyl propargyl ether)則以氮進行攻擊。我們假設這種烯基導向的化學選擇性反應是由於烯基配位到金上時可以加速protodeauration的發生第三章描述了金催化酮炔與苯羥胺(N-hydroxyanilines)進行分子間氧化的一個非典型途徑，此類的氧化反應初始包含了氧鎓化物(oxonium species)的形成，隨即為苯羥胺攻擊，進一步得到氧胺化產物。這個途徑可透過18O標誌實驗得到強力的支持，在一個控制實驗中，我們的產物2-胺基茚酮（2-aminoindenones）也可以經由酮炔與8-甲基喹啉氧化物（8-methylquiniline oxide）及苯胺（aniline）反應得到，但效率很差。第四章展示了四氫異喹啉(tetrahydroisoquinolines)與環醚類化合物(cyclic ethers)的銅催化氧化耦合反應，此反應是經由四級胺產生的SET，形成亞胺離子(iminium ion)來啟動，亞胺離子會與烷自由基耦合形成C1-醚化四氫異喹啉（C1-etherized tetrahydroisoquinoline）。這個方法可以供作設計耦合反應，應用在低親核性但對碳自由基有活性的基質上。

關鍵字

過渡金屬催化；金催化；鉑催化；銅金屬

並列摘要

This dissertation describes development of new synthetic organic transformations by using gold, platinum or copper metal salts. The use of these metals enables mild, selective and efficient oxidative transformations of readily available substrates to wide range of synthetically useful nitrogen, oxygen and sulfur containing complex organic molecules. For better understanding the thesis is divided into four chapters. The first chapter deals with the regiocontrolled hydrations of 1-aryl-3-en-1-ynes with suitable Au(I) and Pt(II), giving 3-en-1-ones and 2-en-1-ones selectively. Herein, we also develop one-pot synthesis of allylic and homoallylic alcohols from these 3-en-1-ynes, through in situ reductions of two ketone products. Our experimental data indicates that the sizes of catalysts play an important role. The second chapter deals with the gold-catalyzed reactions of 1,6-enynes with N-hydroxyanilines to generate kinetically unstable trisubstituted nitrones. Such transient species are efficiently trapped with tethered alkenes to achieve stereospecific cycloadditions. Notably, these annulations involve an atypical N-attack of hydoxyamines at gold--alkynes. Our data reveal that most propargyl ethers show the O-attack selectivity, whereas allyl propargyl ether proceeds exclusively through the N-attack selectivity. This alkene-directed chemoselectivity is postulated to accelerate the protodeauration by an alkene coordination to gold. The third chapter describes an atypical pathway in the gold-catalyzed intermolecular oxidations of ketonylalkynes with N-hydroxyanilines; this oxidation initially involves formation of an oxonium species that is subsequently attacked by N-hydroxyaniline, further leading to oxoamination products. This path is strongly supported by 18O-labeling experiments. In one control experiment, our resulting 2-aminoindenones were alternatively produced from the same ketonylalkynes, 8-methylquiniline oxide and aniline, but the efficiency was low. The fourth chapter presents copper-catalyzed oxidative coupling reactions of tetrahydroisoquinolines with cyclic ethers. These reactions are initiated by SET from a tertiary amine to form an iminium ion which is coupled with alkyl radical to form C1-etherized tetrahydroisoquinoline. This method could open the possibility to design coupling reactions with substrates of low nucleophilicity but reactivity toward carbon radicals.

並列關鍵字

Transition Metal Catalyzed ； Highly Functionalized Organic Frameworks ； Gold-Catalyzed ； Platinum ； Copper

參考文獻

[26] (a) Perkin, W. H. Jun.; Robinson, R. J. Chem. Soc. 1911, 99, 775. (b) Hope, E.; Robinson, R. J. Chem. Soc. 1914, 105, 2085.

[30] (a) Jack, D.; Williams, R. Chem. Rev. 2002, 102, 1669. (b) Bentley, K. W. Nat. Prod. Rep. 2006, 23, 444. (c) Zhang, Q. Y.; Tu, G. Z.; Zhao, Y. Y.; Cheng, T. M. Tetrahedron 2002, 58, 6795. (d) Aladesanmi, A. J.; Kelly, C. J.; Leary, J. D. J. Nat. Prod. 1983, 46, 127. (e) Zhang, A.; Neumeyer, J. L.; Baldessarini, R. J. Chem. Rev. 2007, 107, 274. (f) Ye, K.; Ke, Y.; Keshava, N.; Shanks, J.; Kapp, J. A.; Tekmal, R. R.; Petros, J.; Joshi, H. C. Proc. Natl. Acad. Sci. USA 1998, 95, 1601. (g) Kelleher, C. J.; Cardozo, L.; Chapple, C. R.; Haab, F.; Ridder, A. M. BJU Int. 2005, 95, 81.

[22] Zeng, Q.; Zhang, L.; Yang, J.; Xu, B.; Xiao, Y.; Zhang, J. Chem. Commun. 2014, 50, 4203.

[20] Mukherjee, A.; Dateer, R. B.; Chaudhuri, R.; Bhunia, S.; Karad, S. N.; Liu, R.-S. J. Am. Chem. Soc. 2011, 133, 15372.

[33] Xu, B.; Wang, W.; Hammond, G. B. J. Org. Chem. 2009, 74, 1640.

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過渡金屬催化新轉變為高度官能有機骨架的合成

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