直接非对称的反曼尼克类反应由设计的氨基酸催化
Susumu Mitsumori1, Haile Zhang, Paul Ha-Yeon Cheong
1The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|January 26, 2006
概括
一种新型的催化剂, (3R,5R) -5-甲基-3-罗利丁碳酸 (RR35),使高度选择性的反曼尼克类反应成为可能. 这种有机催化剂在温和条件下,在催化剂负荷较低的情况下,可以实现出色的立体控制和酶选择性.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 不对称的合成方法
背景情况:
- 之前的 (S) - 烯催化产生了syn-Mannich产品.
- 需要催化剂生产具有高选择性的反曼尼克产品.
- 为直接不对称的曼尼赫反应开发有机催化剂.
研究的目的:
- 设计一种新型的催化剂,用于酶选择性和抗选择性曼尼赫类反应.
- 在温和条件和低负载下调查催化剂性能.
- 通过实验合成和测试验证计算预测.
主要方法:
- 基于素催化原理的 (3R,5R) -5-甲基-3-罗利丁碳酸 (RR35) 的设计.
- 使用HF/6-31G*级理论预测催化剂有效性的计算研究.
- 使用未经修改的化物和N-PMP保护的α-imino的实验性有机催化曼尼赫型反应.
主要成果:
- 设计的催化剂 (RR35) 已成功合成.
- 反应产生了具有高二选择性 (anti:syn 94:6 至 98:2) 的抗曼尼克产物.
- 在温和条件下和低催化剂负荷 (1-5 mol %) 下,可以达到优异的酶选择活性 (>97%至>99% ee).
结论:
- 新的RR35催化剂有效地促进了直接的反选择性反选择性曼尼赫型反应.
- 实验结果在数量上与计算预测一致.
- 催化剂提供了一种温和而高效的方法来合成有价值的抗曼尼克产品.
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