樟腦磺醯胺衍生之胺化合物與(2S,4R)-4-羥基-L-脯胺酸之縮合物催化酮類化合物對查耳酮衍生物進行不對稱Michael反應之研究

The Study on Asymmetric Michael Addition Reaction of Ketones to Chalcones Catalyzed by Camphorsulfonamide-Derived (2S,4R)-4-Hydroxy-L-Prolinamide

陳怡如(Yi-Ju Chen)

指導教授 ： 汪炳鈞

國立清華大學/理學院/化學系/碩士(2014年)

摘要

本篇論文旨在研究樟腦磺醯胺衍生之胺化合物與反式-4-羥基-L-脯胺酸縮合之衍生物催化酮類與查耳酮衍生物進行不對稱有機催化Michael反應。篩選最合適之有機催化劑，並探討添加溶劑的種類及用量、添加劑的種類及當量數、反應之溫度、催化劑的當量數對產物產率以及鏡像選擇性的影響；篩選出化合物11d作為最佳的有機催化劑並且應用在催化酮類與各種查耳酮衍生物進行不對稱Michael反應，其中以環己酮作為Michael donor對具有拉電子取代基之查耳酮衍生物進行加成可得到最佳的結果，可達到97%的產率、99:1的非鏡像選擇性，其中syn產物最好可得到93%的鏡像超越值。

關鍵字

不對稱有機催化 ； 不對稱加成反應

並列摘要

This thesis dealt with the synthesis and application of novel prolinamide-camphor organocatalysts that derived from the coupling of trans-4-hydroxy-L-proline and camphorsulfonamide. Organocatalyst 11d is proven to be an efficient catalyst for the asymmetric Michael reaction of ketone and a series of chalcone-derived. Treatment of cyclohexanone with chalcone- deriveds which have electron-withdrawing group using organocatalyst 11d provided the desired Michael products with high chemical yields (up to 97% yield), excellent diastereoselectivities (up to 99/1 dr) and high levels of enantioselectivities (up to 93% ee) for syn- products.

參考文獻

1.Flack, H. D. Acta Crystallagraphica, Section A, 2009, 65, 371.

5.Calne, D. B.; Sandlar, M. Nature 1970, 226, 21.

6.Helmchen, G.; Hoffman, R. W.; Mulzer, J.; Schaumann, E.; Eds.; Stereoselective synthesis, Methods of organic chemistry (Houben- Weyl), Vol. 3, edition E21, Thieme: Stuttgart, Germany, 1996.

7.Perlmutter, P. Conjugate Addition Reaction in Organic Synthesis, Pergamon, Oxford, 1992.

9.Berkessel, A.; Groger, H. Asymmetric Organocatalysis –From Biomimetic Concepts to Applications in Asymmetric Synthesis, Wiley-VCH, Weinheim, 2005.