摘要: 手性酮类化合物普遍存在于具有生物活性的天然产物以及药物分子中，是一类非常重要的有机化合物，其同时也作为合成中间体在有机合成中有着重要的应用。与以往致力于研究手性催化剂催化合成β-手性含氟烷基的酮类化合物的相关报道相比，本文则是介绍了在不使用手性催化剂的情况下，仅利用手性辅基进行诱导，经过进一步的转化和处理，最终合成了β-手性含氟烷基的酮的一种新的合成方法。通过首先使用(R)-叔丁基亚磺酰胺制备了α，β-不饱三氟甲基酮亚胺，再利用格氏试剂作为亲核试剂进行1，4-加成得到β-手性三氟甲基烯胺中间体，最后在盐酸的乙醚溶液中，只需在常温下搅拌水解1h即可水解完全，经过简单处理后得到了预期产物β-手性三氟甲基酮。且当简单地改变反应底物以及格氏试剂时，利用同一种手性辅基，以同样的合成步骤，最后能够顺利得到了目标产物的对映体。61733

毕业论文关键词: α，β-不饱和三氟甲基酮亚胺；(R)-叔丁基亚磺酰胺；格氏试剂；β-手性三氟甲基烯胺；β-手性三氟甲基酮

Studies on the Asymmetric Synthesis of β- Chiral Fluorinated Alkyl Ketones

Abstract:As a kind of important organic compound, chiral ketones was commonly found in bioactive natural products and drug molecule, which is also has important applications as intermediates in organic synthesis. Comparing with the reports of synthesising  the chiral catalyst for the β- chiral fluorinated ketones. In this article, we developed a new method, without using chiral catalyst, we used chiral auxiliary to induce, and get β- chiral fluorinated alkyl ketones after further processing and conversion. Firstly, we completed the preparation of α, β- unsaturated trifluoromethyl ketimine with (R)-tert-butyl sulfonamide, then used the Grignard reagent as the nucleophile for 1,4-addition reaction to get the β- trifluoromethyl chiral enamine intermediate. Finally stirred 1h at room temperature in HCl/Et2O, we could get the desired product β- chiral trifluoromethyl ketone from the hydrolysis of enamine intermediate after a sample process. In addition, when we changed substrate and Grignard reagent, we could get the desired enantiomer in the same procedure by using the same chiral auxiliary.

Keywords:α, β- unsaturated trifluoromethyl ketimine; (R)-tert-butyl sulfonamide; Grignard reagent; β- chiral trifluoromethyl enamine; β- chiral trifluoromethyl ketone

目  录

1  前言 1

1.1  开题依据 1

1.2  文献综述 3

1.2.1  不对称合成 3

1.2.2  羰基类化合物的不对称合成的应用和研究 3

1.2.3  β-手性酮类化合物的不对称合成研究 7

1.2.4  β-手性含氟烷基酮类化合物的不对称合成研究 9

1.3  方案论证 10

1.4  工艺路线的确定 11

1.4.1  α，β-不饱和氟烷基酮亚胺的制备 11

1.4.2  β-手性氟烷基烯胺中间体的制备 12

1.4.3  β-手性氟烷基酮的制备 12

2  实验部分 13

2.1  主要实验仪器 13

2.2  试剂与原料