大学化学 >> 2022, Vol. 37 >> Issue (5): 2111009.doi: 10.3866/PKU.DXHX202111009

所属专题: 第2届全国大学生化学实验创新设计竞赛

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不对称催化合成手性α-氨基酮

文巍, 李朝星, 叶芳秀, 李静烽, 郭其祥()   

  • 收稿日期:2021-11-02 录用日期:2021-11-04 发布日期:2022-03-25
  • 通讯作者: 郭其祥 E-mail:qxguo@swu.edu.cn
  • 作者简介:郭其祥,Email: qxguo@swu.edu.cn
  • 基金资助:
    中央高校基本科研业务费专项资金(SWU119059)

Catalytic Asymmetric Synthesis of Chiral α-Amino Ketones

Wei Wen, Chaoxing Li, Fangxiu Ye, Jingfeng Li, Qixiang Guo()   

  • Received:2021-11-02 Accepted:2021-11-04 Published:2022-03-25
  • Contact: Qixiang Guo E-mail:qxguo@swu.edu.cn

摘要:

“对映异构”是有机化学中的基本概念,也是本科有机化学教学中的重点和难点内容。现有有机化学实验教材中关于对映体合成的实验极其有限,通过不对称催化来实现对映体合成的教学案例尤其少见。本文拟将文献报道的手性布朗斯特酸催化合成α-氨基酮的三组分不对称还原胺化反应开发为教学实验,通过同小组学生使用手性构型不同、取代基不同的催化剂来催化该反应,探究催化剂结构对对映选择性控制结果的影响,并引入核磁共振、比旋光度测定、手性高效液相色谱等分析技术,应用于所合成的手性化合物的结构鉴定、构型判断和对映体过量的测定。这是将现在常规的两组分、非手性合成教学实验升级到多组分、手性合成教学实验的新举措。结果表明,该实验重复性好、时长合适,同时兼具复杂性、探究性和创新性。它的实施有利于学生学习复杂化学反应操作、理解复杂化学反应历程、分析立体选择性控制影响因素以及培养学生进行创新性实验研究的能力。

关键词: 不对称催化, 对映异构, 还原胺化, α-氨基酮, 多组分反应

Abstract:

Enantiomerism, which is a fundamental concept in organic chemistry, is challenging for many undergraduate students. In current laboratory teaching books, asymmetric syntheses are very limited. Particularly, there are few experimental cases for the synthesis of enantiomers via asymmetric catalysis. We rationally designed a comprehensive experiment for the asymmetric catalysis based on a scientific report for use in teaching chemistry experiments. An optically active α-amino ketone is prepared using a chiral Brønsted-acid-catalyzed three-component asymmetric reductive amination reaction of aniline, 2, 3-butanedione, and benzothiazoline. To emphasize the influence of catalysts on the enantioselectivity of product, chiral Brønsted acids with different configurations and steric groups are introduced as catalysts. The target chiral products will then be analyzed using NMR, chiral HPLC, and polarimetry. This experiment effectively upgrades the current popular two-component, achiral synthesis to a multi-component, chiral synthesis. Results indicate that this experiment has good repeatability, is sufficiently challenging, and promotes exploration and innovation. Implementation of this project will benefit students in learning how to manipulate a multi-component reaction, further understand complicated reaction mechanisms, investigate the factors which influence stereoselectivity, and learn how to carry out an innovative experiment.

Key words: Asymmetric catalysis, Enantiomers, Reductive amination, α-Aminoketones, Multi-component reaction

MSC2000: 

  • G64