金(I)離子催化含氮烯炔醇化合物合成非鏡像選擇3,4-雙取代吡咯啶

劉嘉倫(Jia-Lun Liou)

指導教授 ： 葉名倉

國立臺灣師範大學/理學院/化學系/碩士(2010年)

摘要

吡咯啶為許多天然物中常見的單位，因為他們具有高且多樣化的生物活性，所以發展快速且有效率的方法來合成含氮的五員環是相當重要的。本文旨在利用金銀共催化系統對含氮的烯炔醇化物進行分子內克萊森類型重排反應，得到順式的3,4-雙取代吡咯啶衍生物。

丙烯胺與芳香環碘化物在鈀金屬催化下進行Sonogashira反應得到（3-芳香環丙-2-炔)甲苯磺醯胺，接著再和(Z)-1-乙醯氧基-4-溴-2-丁烯進行加成反應，最後加入碳酸鉀，在甲醇及水當溶劑下進行水解，反應得到(Z)-8-芳香環-5-N-甲苯磺醯基-2,7-烯炔-1-醇衍生物。

(Z)-8-芳香環-5-N-甲苯磺醯基-2,7-烯炔-1-醇以二氯甲烷為溶劑，在室溫下與催化劑量的氯化三苯基膦金/三氟甲磺酸銀(Ph3PAuCl/AgOTf)反應，得到順式-3-醯基-4-乙烯基吡咯啶。此反應是經由羥基攻打被金活化的炔基，然後進行分子內克萊森類型重排反應，得到順式-3-醯基-4-乙烯基吡咯啶。X-ray繞射分析證明環化產物中的乙烯基和醯基為順式的。

關鍵字

金催化 ； 烯炔醇 ； 吡咯啶 ； 環化 ； 吡啶 ； 克萊森類型重排

並列摘要

Saturated nitrogen heterocyclic building blocks is great importance in natural product synthesis because of their high and diverse biological activities. Therefore, the development of an efficient method for the synthesis of functionalized nitrogen-containing five-membered ring derivatives is important. In the thesis, we report that gold and silver cocatalyzed intramolecular Claisen-type rearrangement of (Z)-8-Aryl-5-N-tosyl-2,7-enyl-1-ols produces cis-3-acyl-4-alkenylpyrrolidines.
Reaction of (prop-2-yn-1-yl)tosylamine with aryl iodine catalyzed by palladium(0) under Sonogashira reaction conditions produces (3-arylprop-2-yn- 1-yl)tosylamine. Addition of the corresponding (3-arylprop-2-yn- 1-yl)tosylamine to (Z)-4-bromobut-2-en-1-yl acetate followed by hydrolysis of the resulting acetates with K2CO3 in MeOH and H2O afforded the desired tosylamine-tethered 2,7-enyn-1-ols in good yields.
Treatment of the (Z)-8-Aryl-5-N-tosyl-2,7-enyl-1-ols with 10 mol% Ph3PAuCl/AgOTf in CH2Cl2 at 25 ℃ produced cis-3-acyl-4-alkenylpyrroli dines. The reaction proceeded via attack of the hydroxyl group onto the gold-activated alkynes followed by [3,3]-sigamatropic rearrangement to generate cis-3-acyl-4-alkenylpyrrolidines in good yields.Structural elucidation of pyrrolidines was achieved by using X-ray crystallography.

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