以連續性的二次 Michael 加成反應合成多官能基取代環己酮衍生物及其不對稱合成之研究
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2013
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摘 要
本論文分為兩大部分。都是以連續性的二次 Michael 加成反應建構碳-碳鍵的概念，以 [4+2] 的形式合成六員環合環產物。在第一部分中，我們變換起始物 -不飽和-1,3-雙酮 52 的 R2 與 R3 取代基與亞烷基丙二腈 56 的R1 取代基，以得到多樣化的多取代基環己酮結構產物 59；而在第二部分，將引入不對稱催化的概念合成掌性環己酮產物 59’。
第一部分，我們將重心放在探討 alpha,beta-不飽和-1,3-雙酮 52 與二氰乙烯 56 所進行的連續性的二次 Michael 加成反應，此反應具有極高的非鏡像選擇性 (de >99%)。且透過 alpha,beta-不飽和-1,3-雙酮 52、苯甲醛 24 及丙二腈 32 反應的三組分反應也可得到相同的環己酮產物 59，且非鏡像超越值一樣大於 99%。最後將薑黃素引入此連續性的二次 Michael 加成反應的概念中，一樣可得到高非鏡選擇性之環己酮產物。
第二部分，我們延續第一部份的連續性的二次 Michael 加成反應，且加入不對稱催化的概念。以奎寧 (quinine) 為催化劑催化起始物 52 及 56 取得具有兩個掌性中心的多取代環己酮產物 59’，產率為 58-86%，非鏡像超越值大於 99%，鏡像超越值為 57-92%。經過各種反應條件的篩選後，未來或許可以透過在現有的催化劑上修飾，以提升其鏡像選擇性。此部分仍有做進一步延伸的空間。
關鍵字:關鍵字:Michael加成,環己酮,三組分,奎寧
The thesis includes two chapters, and both of them focus on domino double Michael addition. In previous literature reports, intramolecular double-conjugate additions were applied for the synthesis of polycyclic natural compounds. In the first part of this thesis, we reported our efforts in domino double Michael addition of alpha,beta-unsaturated 1,3-diketones 52 to 1,1-dicyanoalkenes 56. The reaction provided 1,1,2,3,6-penta substituted cyclohexanones in good yields and excellent diastereomeric excess value. Furthermore, we have successfully constructed the same type of cyclohexanone derivatives with high de value through three-component reactions. In addition, curcumin can be utilized as the starting material according to our protocol to provide the cyclohexanone product. In the second part, our investigation of organocatalytic asymmetric domino double Michael addition of alpha,beta-unsaturated 1,3-diketones 52 to 1,1-dicyanoalkene 56 was carried out. Two-chiral-centered penta-substituted cyclohexanones 59’ were generated in 58-86% yields, and with good stereoselectivities (> 99% de, 57-92% ee). Further investigation of known organocatalysts to improve the enantioselectivities is currently underway in our laboratory. Key words:Michael addition,cyclohexanone,three-component,quinine
The thesis includes two chapters, and both of them focus on domino double Michael addition. In previous literature reports, intramolecular double-conjugate additions were applied for the synthesis of polycyclic natural compounds. In the first part of this thesis, we reported our efforts in domino double Michael addition of alpha,beta-unsaturated 1,3-diketones 52 to 1,1-dicyanoalkenes 56. The reaction provided 1,1,2,3,6-penta substituted cyclohexanones in good yields and excellent diastereomeric excess value. Furthermore, we have successfully constructed the same type of cyclohexanone derivatives with high de value through three-component reactions. In addition, curcumin can be utilized as the starting material according to our protocol to provide the cyclohexanone product. In the second part, our investigation of organocatalytic asymmetric domino double Michael addition of alpha,beta-unsaturated 1,3-diketones 52 to 1,1-dicyanoalkene 56 was carried out. Two-chiral-centered penta-substituted cyclohexanones 59’ were generated in 58-86% yields, and with good stereoselectivities (> 99% de, 57-92% ee). Further investigation of known organocatalysts to improve the enantioselectivities is currently underway in our laboratory. Key words:Michael addition,cyclohexanone,three-component,quinine
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Michael加成, 環己酮, 三組分, 奎寧, Michael addition, cyclohexanone, three-component, quinine