鈀金屬催化環化反應合成雙取代基亞甲基烯茀與苯并[a]咔唑化合物

Synthesis of Di-substituted methylidenefluorenes and Benzo[a]carbazoles via Palladium Catalyzed Cyclization Reactions

陳景昭(Chin-Chau Chen)

指導教授 ： 吳明忠

高雄醫學大學/藥學院/藥學研究所/博士(2011年)

https://doi.org/10.6832/KMU.2011.00088

摘要

中文摘要

本論文第二章，利用鈀金屬催化2-(1-炔基)聯苯與芳基碘化合物進行偶合環化反應，得到雙取代基亞甲基烯茀化合物。使用2-(1-炔基)聯苯加入3當量芳基碘、5 mol% Pd(OAc)2與2當量K2CO3於DMF/ H2O (10/1)溶媒中加熱至110oC反應。含OCH3、CH3、Cl、Br、CF3取代基之芳基碘，在此方法中反應皆得到良好之產率，唯4-iodonitrobenzene除外。

本論文第三章，使用鈀金屬催化試劑，將烯雙炔化合物轉變成苯并[a]咔唑化合物。以N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines與10 mol%之PdCl2與2當量CuCl2於溶媒THF中加熱至80℃反應，可得到良好產率之苯并[a]咔唑化合物。透過反應機制之研究，證實在反應過程中先形成具鹵素取代之吲哚化合物，繼以鈀(II)金屬催化環化反應生成苯并[a]咔唑。

本論文第四章，使用催化量的碘試劑，亦能促使具有鹵素取代之吲哚化合物，進行環化反應得到苯并[a]咔唑。反應使用N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines加入1.2當量之碘試劑，CH2Cl2為溶媒於室溫下反應，即得到高產率之苯并[a]咔唑化合物。在某些例子，當反應物具備t-butyl取代基與拉電子基取代基者，反應則停留在第一次環化反應所形成的吲哚化合物，而非苯并[a]咔唑化合物。

關鍵字

鈀 ； 亞甲基烯茀 ； 苯并[a]咔唑

並列摘要

Abstract

In chapter two, the palladium-catalyzed annulation reaction of 2-(1-alkynyl)biphenyls with aryl iodides to give diarylmethylidenefluorenes is described. Specifically the pertinent synthesis involves 2-(1-alkynyl)biphenyls with 3 equivalents of aryl iodides in DMF/ H2O (10/1) in the presence of 5 mol % of Pd(OAc)2 and 2 equivalents of K2CO3 at 110oC. This method tolerates various functional groups in aryl iodide, such as OCH3, CH3, Cl, Br, CF3 and NO2. All proceed in good yield with the exception of 4-iodonitrobenzene.

In chapter three, the palladium-catalyzed cyclization of enediynes to benzo[a]carbazoles is described. Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines with 10 mol% of palladium dichloride and 2 equivalents of cupric chloride in refluxing THF gave benzo[a]carbazoles in good yields. A mechanistic study showed that this reaction must proceed through formation of haloindole followed by a palladium(II)-catalyzed atom transfer cyclization reaction to give the benzo[a]carbazoles.

In chapter four, we found iodine can also catalyzed the cyclization of haloindoles to give benzo[a]carbazoles. Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines with 1.2 equivalents of iodine in CH2Cl2 at room temperature gave benzo[a]carbazoles in good yields. In some cases, while the substrates bearing t-butyl at the terminal alkyne or electron withdrawing group at the amine, the reaction stop at the haloindoles rather than benzo[a]carbazoles.

並列關鍵字

palladium ； methylidenefluorenes ； benzo[a]carbazoles

參考文獻

參考文獻

1. (a) Wang, C.; Batsanov, A. S.; Bryce, M. R. J. Org. Chem. 2006, 71, 108. (b) Mills, N. S.; Tirla, C.; Benish, M. A.; Rakowitz, A. J.; Bebell, L. M.; Hurd, C. M. M.; Bria, A. L. M. J. Org. Chem. 2005, 70, 10709. (c) Ito, S.; Inabe, H.; Morita, N.; Tajiri, A. Eur. J. Org. Chem. 2004, 1774.

2. (a) Martín-Gomis, L.; Ortiz, J.; Fernández-Lázaro, F.; Sastre-Santos, A´.; Elliott, B.; Echegoyen, L. Tetrahedron 2006, 62, 2102. (b) Heeney, M.; Bailey, C.; Giles, M.; Shkunov, M.; Sparrowe, D.; Tierny, S.; Zhang, W.; McCulloch, I. Macromolecules 2004, 37, 5250. (c) Wong, W.-Y.; Lu, G.-L.; Choi, K.-H.; Lin, Z. Eur. J. Org. Chem. 2003, 365.

3. (a) Grisorio, R.; Mastrorilli, P.; Ciccarella, G.; Suranna, G. P.; Nobile, C. F. Tetrahedron Lett. 2008, 49, 2078. (b) Perepichka, D. F.; Bryce, M. R.; Batsanov, A. S.; McInnes, E. J. L.; Zhao, J. P.; Farley, R. D. Chem. Eur. J. 2002, 8, 4656. (c) Perepichka, D. F.; Bryce, M. R.; Perepichka, I. F.; Lyubchik, S. B.; Christensen, C. A.; Godbert, N.; Batsanov, A. S.; Levillain, E.; Mclnnes, E. J. L.; Zhao, J. P. J. Am. Chem. Soc. 2002, 124, 14227. (d) Perepichka, D. F.; Bryce, M. R.; Mclnnes, E. J. L.; Zhao, J. P. Org. Lett. 2001, 3, 1431.

4. (a) Mills, N. S.; Tirla, C.; Benish, M. A.; Rakowitz, A. J.; Bebell, L. M.; Hurd, C. M. M.; Bria, A. L. M. J. Org. Chem. 2005, 70, 10709. (b)Mills, N. S.; Benish, M. A.; Ybarra, C. J. Org. Chem. 2002, 67, 2003. (c) Mladenova, G.; Chen, L.; Rodriquez, C. F.; Siu, K. W. M.; Johnston, L. J.; Hopkinson, A. C.; Lee-Ruff, E. J. Org. Chem. 2001, 66, 1109. (d) Mills, N. S.; Malinky, T.; Malandra, J. L.; Burns, E. E.; Crossno, P. J. Org. Chem. 1999, 64, 511. (e) Luisa, M.; Franco, M. B.; Herold, B. J. J. Chem. Soc., Perkin Trans. 2 1988, 443. (f) Murphy, W. S.; Hauser, C. R. J. Org. Chem. 1966, 31, 85.