1.新有機催化劑之開發及其在不對稱合成之探討；2.含有樟腦分子架構之對掌硫尿素-L-脯胺酸有機催化劑在不對稱Aldol反應之研究

Abstract

本論文共分兩大部分：第一部分為本實驗室所合成的5-oxo-1-phenyl- pyrazolidine-3-carboxylic acid 37進行光學分割，得到高光學純度的新有機催化劑。以L-Val甲基酯之雙肽衍生物46利用管柱層析可簡易地分離純化，產率為86%，並在酸性條件下水解，即可得到光學純度高的(+)-(R)-及(-)-(S)-5-oxo-1-phenyl-pyrazolidine-3-carboxylic acid 37，其產率分別為94%及95%。將此新有機催化劑應用於催化直接不對稱aldol反應，以水當溶劑，產率可達52%、鏡像超越值達51%。 第二部分為本實驗室所設計的含樟腦分子架構之對掌硫尿素-L-脯胺酸有機催化劑110a-e可以被有效地合成製備；其亦可成功地應用在直接不對稱aldol反應，以水為溶劑的條件下，主要得到anti的aldol產物，且有極高的化學產率（95%）、高非鏡像及高鏡像選擇性（anti/syn = 96/4、> 99% ee）。

The dissertation is divided into two sections, they are as follows: Ⅰ、Optical resolution of racemic 5-oxo-1-phenyl-pyrazolidine-3-carboxylic acid 37 with L-amino acid methyl ester via the diastereomers formation were investigated. Treatment of racemic 5-oxo-1-phenyl-pyrazolidine-3- carboxylic acid 37 with L-valine methyl ester give the diastereomers 46 with a total of 86% yield. The diastereomeric dipeptides can be easily separated by flash column chromatography. Acidic cleavage of the derived diastereomers to give both the optically pure (+)-(R)- and (-)-(S)-5-oxo- 1-phenyl-pyrazolidine-3-carboxylic acid（(+)-(R)-37 and (-)-(S)-37）with a total of 94% and 95% yield, respectively. The new organocatalyst was used as a catalyst for direct asymmetric aldol reaction in the presence of water to achieve 52% chemical yield and 51% ee. Ⅱ、The bifunctional thiourea-amine organocatalysts bear a hydrophobic camphor scaffolding, which can be readily synthesized with good overall chemical yields. The new organocatalysts 110a-e were successfully used as a catalyst for direct asymmetric aldol reaction to afford the anti products with excellent chemical yield and diastereo- and enantioselectivity in the presence of water.