(一) 中心掌性轉換成軸掌性策略：不對稱合成 3-苯並呋喃基吲哚阻轉異構物 (二) 羥基芳基磺醯基吲哚生成插烯亞胺中間體與丙二腈經不對稱麥可加成/環加成/互變異構化反應合成2-胺基-4-氫-

I Asymmetric Synthesis of 3-Benzofuran-2-yl-indoles Atropisomers through Conversion from Central to Axial Chirality II Asymmetric Synthesis of 2-Amino-4H-chromenes via Michael Addition/Cyclization/Tautomerization Reaction of Malononitrile and Vinylogous Imine Intermediates Generated from Hydroxy Arylsulfonyl Indoles

薛智允(Hsueh Chih-Yun)

指導教授 ： 林文偉

國立臺灣師範大學/理學院/化學系/碩士(2023年)

https://doi.org/10.6345/NTNU202300817

摘要

第一部分：
利用羥基芳基磺醯基吲哚及 α-溴苯乙酮在鹼性條件下會形成插烯亞胺中間體，隨後再進行麥可加成反應、 (4+1) 合環反應得到 3-(2,3-二氫呋喃基)-吲哚，再經由氧化合成出 3-(苯並呋喃基)-吲哚。對於氧化成 3-(苯並呋喃基)-吲哚已做了一些實驗，不過目前尚無法合成出 3-(苯並呋喃基)-吲哚。
由於 α-溴苯乙酮作為起始物會產生少許副產物，使得產率不佳。因此將其更換成同是作為一個碳源的合成子起始物，N-苯甲醯甲基吡啶鹽類，解決了使用 α-溴苯乙酮而發生副反應的問題。此外也透過控制實驗的比較，提出了可能的反應機構。

此部分仍用一樣的起始物羥基芳基磺醯基吲哚，僅更換不同的親核試劑，丙二腈。在鹼性條件下，羥基芳基磺醯基吲哚會先形成插烯亞胺中間體再與丙二腈進行麥可加成/環加成/互變異構化不對稱反應合成 2-胺基-4氫-

關鍵字

羥基芳基磺醯基吲哚 ； α-溴苯乙酮 ； 插烯亞胺中間體 ； 3-(2,3-二氫呋喃基)吲哚 ； (4+1) 合環反應 ； 丙二腈 ； 2-胺基-4-氫- ； 有機催化

並列摘要

Under basic conditions, the hydroxy arylsulfonyl indoles first form vinylogous imine intermediates and then undergo Michael addition and (4+1) cycloaddition reaction to provide 3-(benzofuran-2-yl)-indoles. However, the use of α-bromoacetophenones resulted in poor yields due to the formation of byproducts. Therefore, N-benzoylmethylpyridinium salts are used as starting materials instead to avoid the side reactions. Additionally, we investigate the reaction mechanism of hydroxy arylsulfonyl indoles and α-bromoacetophenone and identified a possible mechanism through control experiments.

This section also uses the same starting materials, hydroxy arylsulfonyl indoles, and only changes the different nucleophilic reagent, malononitrile. Under basic conditions, the hydroxy arylsulfonyl indoles first form an vinylogous imine intermediates. Then the vinylogous imine intermediates react with malononitrile via asymmetric Michael addition/cyclization/tautomerization to provide 2-amino-4H-chromene derivatives.
Because the reactivity of the starting materials, hydroxy aryl sulfonyl indoles, are poor, we believe that the protecting group of indoles can significantly improve its reactivity. Currently, the reaction conditions can be optimized to achieve a yield of products up to 67% with up to 74% ee.
In addition, hydroxy arylsulfonyl indoles are replaced with amino arylsulfonyl indoles so that its products are expected to be possibly oxidized to obtain axial chirality compounds.
To expand the application of this synthetic strategy, different frameworks of arylsulfonyl-protected starting materials are also proposed in our preliminary study, such as 4-hydroxy arylsulfonyl coumarins and 2-hydroxy arylsulfonyl naphthoquinones.

並列關鍵字

hydroxy arylsulfonyl indole ； α-bromoacetophenone ； vinylogus imine ； 3-(benzodihydrofuran-2-yl) indole ； (4+1) cycloaddition ； malononitrile ； 2-amino-4H-chromene derivatives ； Michael addition ； organocatalyst

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