鹼催化分子內羥基三鍵加成反應之密度泛函理論研究

Density Functional Theory Study of Base-Assisted Intramolecular Alkyne Hydroalkoxylation

王雅柏(Ya-Po Wang)

指導教授 ： 陳信允

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2013年)

https://doi.org/10.6832/KMU.2013.00091

摘要

許多具有生物活性分子都有含氧雜環的結構，也因此含氧雜環的合成方法也愈來愈受到重視。羥基三鍵加成的分子內環化反應即是最佳方法之一。本文利用密度泛函理論，M06-2X/6-31+G*理論層級，探討以羥基三鍵加成之分子內環化反應的可能路徑。在此推估可能的路徑有二；先以羥基加成到炔上後質子轉移的alkyne路徑以及先質子轉移形成allene形式的結構後再環化的allene路徑。我們共探討了四種不同炔末端取代基，分別為氫、phenyl、anisole及trifluoromethyl benzene.計算結果顯示，在缺少鹼(K2CO3)的幫助下環化反應無法生成。四個不同取代基所呈現的結果，皆傾向以allene路徑進行環化反應。

關鍵字

密度泛函 ； 鹼 催化 ； 反應機制 ； 含氧雜環

並列摘要

Oxygen-containing heterocycles are present in a wide range of bioactive products. Synthesis methods of such heterocycle are growing importance. The addition of O-H nucleophile to alkyne represents one of the great methods. In this thesis, density functional theory of M06-2X/6-31+G* theory level was employed to investigate the base-assisted intra-molecular alkyne hydroalkoxylation reaction. It is assumed that there are two possible pathways; the “alkyne path” in which the cyclization directly occurs via the nucleophilic addition of the hydroxyl group on the alkyne, and the “allene path” where the allene intermediate is formed prior to the cyclization. Four terminal substituents (including hydrogen, phenyl, anisole and trifluoromethyl benzene) have been calculated.Our calculations show that, in the absence of the K2CO3 the intramolecular cyclization reaction cannot take place. For all the four molecular systems under investigation, the allene pathway is more favorable.

並列關鍵字

DFT ； mechanism

參考文獻

1 Gilmore, K.; Alabugin, I. V. Chem. Rev. 2011, 111, 6513-6556.

2 (a) Godoi, B.; Schumacher, R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937-2980.

(b) Yang, F.; Jina, T.; Bao, M.; Yamamoto, Y. Tetrahedron 2011, 67, 10147-10155.

3 Seo, S.Y.; Yu, X.; Marks, T. J. J. Am. Chem. Soc. 2009, 131, 263-276.

4 Huo, Z.; Gridnev, I. D.; Yamamoto, Y. J. Org. Chem. 2010, 75, 1266-1270.