基拉尔布伦斯特德酸催化了反选择性曼尼赫型反应
Masahiro Yamanaka1, Junji Itoh, Kohei Fuchibe
1Contribution from the Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro Toshima-ku, Tokyo 171-8588, Japan. myamanaka@rikkyo.ac.jp
Journal of the American Chemical Society
|May 5, 2007
概括
化酸催化剂使基基乙烯和胺之间能够有效地进行曼尼赫式反应,产生高度反选择性的β-氨基乙烯. 优化的催化剂和特定的胺结构对于高立体选择性至关重要.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
- 机体催化剂是有机催化剂.
背景情况:
- 曼尼赫类反应是有机合成中基本的碳-碳键形成反应.
- 开发对曼尼赫反应的酶选择性方法对于合成奇拉分子至关重要.
- 奇拉尔·布伦斯特德酸,特别是酸衍生物,已经成为不对称转换的强大催化剂.
研究的目的:
- 开发一种新型的催化系统,用于 ketene silyl acetals 与 aldimines 的不对称的曼尼赫式反应.
- 为了获得高产量,在形成β-氨基乙烯的过程中实现了二聚体选择性 (syn异构体) 和酶选择性 (enantioselectivity).
- 用计算方法阐明反应机制并了解控制立体选择性的因素.
主要方法:
- 催化曼尼赫式反应采用从 (R) -BINOL中衍生出来的性酸二聚体.
- 系统地改变催化剂替代剂和胺结构以优化反应结果.
- 密度函数理论 (DFT) 计算 (BHandHLYP/6-31G*) 用于研究反应路径和过渡状态.
主要成果:
- 成功的催化曼尼赫类反应,产生具有高反选择性 (高达96% ee) 的β-氨基和良好的 syn同位素的二聚选择性.
- 鉴定一种酸二聚,在BINOL的3,3'-位置上有4 - - 尼托芬基,作为最有效的催化剂.
- 证明了N-2-基基在阿尔迪米因基质中对反应效率的重要作用.
- 理论计算支持了一条涉及九个成员周期过渡状态的非协调路径,解释了观察到的重面选择性和硬质障碍的影响.
结论:
- 通过使用性酸二体,已经建立了一个高度选的催化曼尼赫类反应.
- 反应机制通过非协调路径进行,通过DFT计算进行合理化,突出突出催化剂结构和基质特征的重要性.
- 这种方法提供了一条有效的途径,以获得有价值的性β-氨基.
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