一、新有機催化劑的設計與製備 二、L-脯胺酸衍生之有機催化劑在動力學分割反應之探討

I. The Design and Synthesis of New Organocatalyst II. L-Proline Derived Organocatalysts for the Kinetic Resolution

陳思涵(Szu-Han Chen)

指導教授 ： 陳焜銘

國立臺灣師範大學/理學院/化學系/碩士(2010年)

摘要

本論文共分為兩大部分：第一部分為合成外消旋化合物5-(hydroxydiphenyl- methyl)-2-phenylpyrazolidin-3-one 42，並進行光學分割，成功接上對掌樟腦分子，利用管柱層析分離可得到(R)-form樟腦磺酸衍生物46，但無論使用酸性、鹼性或還原劑的方式，都無法順利將光學分割劑樟腦分子切割，無法得到高光學純度的(R)-form催化劑42。
第二部份為利用本實驗室所合成的L-脯胺酸衍生之有機催化劑，應用於不對稱共軛加成-脫去反應，以正戊醛166和allylic acetate 163作為起始物，篩選最佳有機催化劑、改變溶劑種類、添加劑效應、催化劑和正戊醛166的當量數、改變反應溫度、更換取代基，探討對產物產率和鏡像選擇性之影響，篩選出以20 mol%的催化劑和4當量正戊醛166，在-20 oC下以二甲苯為溶劑，且不須添加酸添加劑為最佳反應條件，當使用不同取代基之allylic acetate 168時，可得到產率26 ~ 40%，鏡像超越值高達98 ~ 99% ee；將起始物allylic acetate進行回收，可得到產率16 ~ 48%，鏡像超越值83 ~ 96% ee。由此結果，我們推測此反應是經由共軛加成-脫去反應來進行動力學分割，反應機構亦加以探討。

關鍵字

有機催化 ； 動力學分割 ； 脯胺酸

並列摘要

The dissertation is divided into two sections, they are as follows:
The first part to prepare racemic 5-(hydroxydiphenylmethyl)-2-phenyl- pyrazolidin-3-one 42 and carried out optical resolution. Treatment of racemic 5-(hydroxydiphenylmethyl)-2-phenylpyrazolidin-3-one 42 with chiral camphor
sulfonic acid and separated by flash column chromatography to obtain (R)-46. But using acid、base and reduction reagent can’t successfully cleavage of resolving agent to give the optically pure organocatalyst (R)-42.
The second part to study L-proline derived organocatalysts 155 ~ 162 and 102 for asymmetric conjugate addition-elimination of valeraldehyde 166 to allylic acetate 163. Herein, we choose the best organocatalyst, study the solvent effects, and so on. The reaction was carried out by using the valeraldehyde 166 (4.0 equiv) and allylic acetate 163 as the starting materials in xylene in the presence of catalyst 102 (20 mol%). The chemical yields of the desired product is up to 40% and ee value can be up to 99% ee. And the recovery of the allylic acetate is up to 48% and up to 96% ee. Therefore, we developed a novel kinetic resolution via asymmetric conjugate addition-elimination.

並列關鍵字

Organocatalytic ； Kinetic Resolution ； proline

參考文獻

2. List, B.; Lerner, R. A.; Barbas, C. F. Ⅲ. J. Am. Chem. Soc. 2000, 122, 2395.

3. Jacobsen, E. N.; Doyle, A. G. Chem. Rev. 2007, 107, 5713

4. Bertelsen, S.; Nielsen, M.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2007, 46, 7356.

5. List, B. Chem. Commun. 2006, 819.

7. (a) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2007, 129, 10054. (b) Ramasastry, S. S. V.; Zhang, H.; Tanaka, F.; Barbas, C. F. Ⅲ. J. Am. Chem. Soc. 2007, 129, 288. (c) Yang, J. W.; Stadler, M.; List, B. Angew. Chem. Int. Ed. 2007, 46, 609.