摘要：

本文选取抗艾滋病药物安普那韦的中间体(Ⅰ)以及氨基醇化合物(Ⅱ)为原料,通过一系列合成手段,最终得到非对称的单噁唑啉吡啶类配体(Ⅲ,Ⅳ)和C2-对称的双噁唑啉吡啶类配体(Ⅴ),并研究它们对一些标志性催化反应的催化活性.论文主要完成了以下工作: 1.以化合物(Ⅰ)为原料,通过立体选择性的还原,去保护基等步骤合成了手性氨基醇(Ⅵ),再与2-吡啶甲酸反应形成吡啶酰胺化合物(Ⅶ),然后通过叔丁基二甲基硅基(TBS)保护和甲磺酰化,最后用正丁基锂环合得到噁唑啉吡啶类手性配体(Ⅲ). 2.以氨基醇化合物(Ⅱ)为起始手性源,分别与2-吡啶甲酸和2,6-吡啶二甲酰氯反应,然后依次通过去Boc保护和苯甲酰化,最后环合得到单噁唑啉吡啶类配体(Ⅳ)和C2-对称的双噁唑啉吡啶类配体(Ⅴ). 3.研究了手性配体(Ⅲ,Ⅳ,Ⅴ)在二乙基锌与苯甲醛加成反应中的催化效率和不对称诱导效应.Ⅲ和Ⅳ对反应的催化活性有较大差别,说明噁唑啉环C-5'位上的不同取代基对催化活性是有较大影响的.非对称的单噁唑啉吡啶类配体Ⅳ与C2对称的手性配体Ⅴ在催化反应中得到的产物的绝对构型相反,且手性配体Ⅴ较Ⅳ的催化性能高. 4.选择了手性配体(Ⅳ,Ⅴ)与醋酸铜形成的配合物作为催化剂,对硝基甲烷与苯甲醛的不对称Henry反应进行催化,发现手性配体Ⅳ较Ⅴ的催化性能高,ee值分别为50.3%和24.5%.所得到的产物绝对构型相反,本文提出了可能的反应机理.Chiral pyridine mono(oxazoline) ligands (Ⅲ,Ⅳ) and C2-symmetric bis(oxazoline) ligand (Ⅴ) have been synthesized from one intermidiate (Ⅰ) of anti-AIDS drug Amprenavir and chiral amino alcohol (Ⅱ) as starting material through a series of approaches. In addition, we demonstrate the effectiveness of the ligands in some typical asymmetric benchmark-reactions, the diethylzinc addition to benzaldehyde and Henry reaction. Our main works are as following: 1. Pyridine amide (Ⅶ) was synthesized by diastereoselective reaction of the compound (Ⅰ) to form the alcohol chial center, deprotection to give the key amino alcohol (Ⅵ), coupling with picolinic acid. Pyridine mono(oxazoline) ligand (Ⅲ) was provided using TBS as protectional group, converted mesylate derivative and ring closure with n-BuLi. 2. Chiral ligands (Ⅳ) and (Ⅴ) were synthesized from amino alcohol (Ⅵ) which acts as both chiral source and starting material. The amino alcohol (Ⅵ) was converted to the corresponding hydroxyl amides after reaction with picolinic acid and pyridine-2,6-dicarbonyl dichloride respectively. After deprotection the Boc and benzoylation, pyridine mono(oxazoline) ligand (Ⅳ) and bis(oxazoline) ligand (Ⅴ) were synthesized by cycling in the presence of MsCl. 3. The chiral ligands (Ⅲ,Ⅳ,Ⅴ) were used as catalyst to promote the asymmetric addition of diethylzinc to benzaldehyde. The calalytic capability of the ligand (Ⅲ) and ligand (Ⅳ) was quite different, which shows that the substituent groups on C-5' have great effect on the enantioselectivity. It was showed that the mono(oxazoline) ligand (Ⅳ) and C2-symmetric bis(oxazoline) ligand (Ⅴ) induced the product with two opposite absolute configuration. In addition, C2-symmetric bis(oxazoline) ligand (Ⅴ) shows better catalytic capability than the mono(oxazoline) ligand (Ⅳ). 4. Chiral ligands (Ⅳ) and (Ⅴ) and their complexes with acetate copper were used as enantioselective catalysts in asymmetric Henry reaction of benzaldehyde with nitromethane. Investigation indicated that the mono(oxazoline) ligand (Ⅳ) gave higher enantioselectivity (50.3% ee) than the C2-symmetric bis(oxazoline) ligand (Ⅴ) (24.5% ee). A plausible mechanism for the opposite absolute configuration was proposed.

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