有機催化劑的設計合成及其在Michael加成反應之應用

The Design and Synthesis of the Organocatalyst and the Application of Michael Reactions

李思憲(Ssu-Shing Li)

指導教授 ： 陳焜銘

國立臺灣師範大學/理學院/化學系/碩士(2007年)

摘要

Michael加成反應可建構新的碳-碳鍵，為不對稱合成的重要反應形式之一，可應用在天然物與藥物合成上。利用有機催化劑進行不對稱Michael加成反應，是一符合經濟效益與環保的不對稱合成方法。以L-脯胺酸進行不對稱Michael加成反應可得到良好的產率與鏡像超越值，因此L-脯胺酸衍生之有機催化劑的合成與開發逐漸成為研究重要的議題。
本篇論文結合了本實驗特有的樟腦架構，及對掌硫尿素設計合成新的有機催化劑62及63，催化Michael加成反應及Baylis-Hillman反應，探討了不同溶劑對於反應的影響，結果並無法得到我們預期，未來將在針對其他反應做探討，相信有機催化劑62及63還是有其應用價值。
另外也結合樟腦架構與L-脯胺酸設計新的有機催化劑64。以β-硝基苯乙烯與異丁醛為反應物，進行不對稱有機催化Michael加成反應，改變不同溶劑種類、催化劑的劑量數、更換不同添加劑及取代基，探討對產物鏡像選擇性的影響，篩選出在室溫下以飽和食鹽水為溶劑，添加20 mol%催化劑64與20 mol%的苯甲酸為最適宜反應條件，產率為62 %，鏡像超越值達81% ee。取代基若為環戊醛結果最佳，產率可達80%，鏡像超越值高達90% ee，以不同的β-硝基乙烯與環戊醛為起始物，可得到產率為70-80%，鏡像超越值皆可達88% ee。
推測反應機構為由樟腦架構提供立體障礙，使催化劑64與醛類形成特定位向的烯胺，有機催化劑上的羥基會與β-硝基苯乙烯的硝基產生氫鍵，而得到高立體選擇性的產物。

關鍵字

有機催化

並列摘要

Michael addition reaction can create a new carbon-carbon bond and it is one of the important methods in asymmetric syntheses. It is useful in nature product and medicine synthesis. It has economic benefits and environmental protection to do asymmetric Michael addition by utilizing organic catalyst. The L-proline is one of the most well-known organocatalysts used in Michael addition, with high yield and enantioselective excess. How to introduce new functional groups into L-proline to get better result becomes more and more important.
This thesis discuss about the design of new type of organocatalyst. The new organocatalysts 62 and 63 combining camphor and thiourea has been designed and synthesized. Although they can’t get good result in Michael addition and Baylis-Hillman reaction, the ideal of design bifuctional catalyst with combining camphor and thiourea is creative and valuable.
In addition, the new type of organocatalyst 64 combining camphor and L-proline has also been designed and prepared. It shows excellent result to couple β-nitrostyrene and isobutylaldehyde via Michael addition. Herein, we also discuss the effect of solvent, additive, and so on. Furthermore the reaction was treated in brine in the presence of catalyst 64 (20 mol%) and benzoic acid (20 mol%). The yield of desired product is up to 80% and ee value can go up to it’s maximum (90% ee).

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