新型轴手性双膦配体的合成及其在不对称氢化中的应用

SYNTHESIS OF NOVEL ATROPISOMERIC BISPHOSPHINE LIGANDS AND THEIR APPLICATIONS IN ASYMMETRIC HYDROGENATION

杨春艳

11849228

硕士

化学工程领域工程

张绪穆

2020-06-02

2020-07-20

哈尔滨工业大学

深圳

在不对称催化氢化合成领域的研究过程中，手性催化剂的存在是反应高效和高选择性的原因。手性膦配体作为催化剂的重要组成部分，受到了广泛的研究，其中，轴手性双膦配体的研究最多。然而，以联苯类或联萘类为骨架的轴手性双膦配体大都具有较长的合成步骤和偏低的收率，因而，工业化应用价值大大降低。因此，设计一类新型轴手性双膦配体，其具有高收率、高效性和高选择性等优势，这对工业化应用是十分有必要的。本研究分析了轴手性双膦配体合成困难的原因，基于NUPHOS的设计理念和合成路线，本文设计了一类新型轴手性双烯双膦配体，并通过锆环金属化反应和双炔环化反应进行合成。具体研究内容如下：以(R, R)-1, 2-环己烷二甲酸为原料，经三步或者四步反应合成了两个新配体，产率达到了66%。当苯乙酮作为反应底物，只有把新配体制成双膦双胺催化体系时，苯乙酮及其衍生物的不对称催化才取得了好的结果，达到了与BINAP双膦双胺催化体系相当的催化活性。以2-特戊酰胺基-1-茚满酮作为标准底物，检测新配体的催化活性和对映选择性。反应转化率达到了99%，以96% ee得到产物，产物为有机合成中非常有用的手性胺基酮类化合物。拓展了反应的底物适用范围，完成了16个底物的不对称催化氢化反应实验，产物对映体过量最高可达到99% ee。

In the research process of asymmetric catalytic hydrogenation synthesis, the existence of chiral catalyst is the reason for the high efficiency and high selectivity of the reaction. Chiral phosphorus ligands are an important part of catalysts and have been extensively studied, with atropisomeric bisphosphine ligands as the most. However, most of the atropisomeric bisphosphine ligands based on biphenyls or binaphthalenes have long synthesis steps and low yields, and the industrial application value is greatly reduced. Therefore, a new class of novel atropisomeric bisphosphine ligands is designed which have high yields, and have high efficiency and high selectivity. It is very necessary for industrial application.This study analyzes the reasons for the difficulty in the synthesis of atropisomeric bisphosphine ligands. Based on the design concept and synthetic route of NUPHOS, a new type of novel atropisomeric bisphosphine ligands was designed and synthesized using metallacycle transfer from zirconium and dialkyne cyclization. The specific research content is as follows: Using (R, R) -1,2-cycloxylene as raw materials, two new ligands were synthesized through three-step or four-step reaction, reaching 66% yield. When acetophenone is used as the reaction substrate, only when the new ligand is made into a bisphosphine diamine catalytic system, the asymmetric reduction of the catalytic hydrogenation of acetophenone and its derivatives has achieved good results, reaching a catalytic activity comparable to the BINAP bisphosphine diamine catalyst system. 2-pivalamido-1-indanone is the standard substrate. The catalytic activity and enantioselectivity of new ligands are detected and good results are obtained by asymmetric reduction. The conversion rate reaches 99%, and the product are obtained with 96% ee. They are very useful chiral amino ketone compounds in organic synthesis. The application scope of the reaction substrate is expanded. The asymmetric catalytic hydrogenation experiment of 16 substrates is completed, and the enantiomeric excess of the product can reach 99% ee.

新型轴手性双膦配体 锆环金属化反应 双炔环化反应 环状α-脱氢胺基酮

novel atropisomeric bisphosphine ligands metallacycle transfer from zirconium dialkyne cyclization cyclic α-dehydroamino ketones

中文

联合培养

南方科技大学

杨春艳. 新型轴手性双膦配体的合成及其在不对称氢化中的应用[D]. 深圳. 哈尔滨工业大学,2020.