樟腦分子架構衍生之有機催化劑合成與其在動力學分割之應用

Abstract

本實驗室利用有機催化的概念設計出以二級胺為活化中心，樟腦分子架構為立障中心之有機催化劑，在不對稱催化反應中皆有不錯的表現。另一方面，利用動力學分割，將外消旋化合物的兩個異構物進行分離，成功地製備出高光學純度的對掌純物質，也是本實驗室的研究主題。本篇論文以Baylis-Hillman得到的外消旋起始物和酮類化合物作用，進行不對稱共軛加成-脫去反應，以改變起始物掌性中心的方式，提昇產物的鏡像超越值，同時利用動力學分割，將外消旋化合物進行分離，得到高鏡像選擇性之產物及起始物。 利用本實驗室所開發之有機催化劑(116, 119-123, 139)，以外消旋混合物allylic acetate 133，3當量的環己酮19為起始物，進行不對稱共軛加成-脫去反應。經過一系列反應條件的篩選之後，篩選出在甲基第三丁基醚為溶劑、0 oC下，20 mol%的催化劑139進行反應，可得到最佳的結果，產物138c之產率為40%，鏡像選擇性94% ee；回收起始物133c之產率為35%，鏡像選擇性為89% ee。

Since last few years, our group has been focusing on the design and synthesis of pyrrolidinyl-camphor derived organocatalysts for the asymmetric reactions. These novel pyrrolidinyl-camphor derived organocatalysts have proven to be very effective in asymmetric synthesis. Kinetic resolution is one of the conventional methods to obtain enantiomerically enriched compounds from racemic mixtures. Herein, we have developed pyrrolidinyl-camphor derived organocatalysts for the kinetic resolution of nitroallylic acetates (derived from the Baylis-Hillman reaction) via conjugate addition-elimination reaction using ketones as a donor. In the beginning, we have employed pyrrolidinyl-camphor derivatives (116, 119-123, 139) in the reaction of cylcohexanone 19 to nitroallylic acetate 133 via conjugate addition-elimination pathway. After extensive optimization studies, the reaction was carried out in MTBE at 0 oC, in the presence of 20 mol% of organocatalyst 139. The densely functionalized product 138c was obtained with high chemical yield (40%) and excellent enantioselectivity (94% ee), and the acetate 133c was recovered with moderate chemical yield (35%) and good enantioselectivity (89% ee).