有机催化和高度立体选择的直接维尼洛基Mannich反应
Tian-Yu Liu1, Hai-Lei Cui, Jun Long
1Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Journal of the American Chemical Society
|February 1, 2007
概括
一种新型的非对称维尼洛基曼尼赫反应,使用一种性器官催化剂,可有效合成有价值的三角氨基酸. 这种方法在室温下提供了高选择性和广泛的基板范围.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
背景情况:
- 曼尼赫反应是有机合成中的一个基本的碳-碳键形成反应.
- 开发不对称的变体对于获取质纯化合物至关重要.
- 直接不对称的维尼洛基曼尼赫反应的研究较少,特别是对具有挑战性的基质,如α,α-dicyanoolefins.
研究的目的:
- 开发了第一个直接的非对称维尼洛格曼尼赫 (AVM) 反应的alpha,alpha-dicyanoolefins和N-Boc aldimines.
- 为了确定一个高效和有选择性的有机催化剂进行这种转化.
- 为了证明添加物的实用性,以合成纯净的德尔塔氨基酸.
主要方法:
- 使用了一种性双功能氨酸-三级胺器官催化剂.
- 进行了alpha,alpha-dicyanoolefins和N-Boc aldimines之间的反应.
- 优化反应条件,包括催化剂负荷,温度和溶剂.
- 分析产品的立体化学,使用合性高性能液体染色学 (HPLC).
主要成果:
- 首次实现了阿尔法,阿尔法-二基亚诺烯和N-Boc胺的直接非对称维尼洛基曼尼赫反应.
- 反应以高效率进行 (基质与催化剂的比率高达1000).
- 显示出出色的区域和立体选择性 (一般>99%的二聚体过量和96到>99.5%的反聚体过量).
- 这种反应在室温下对广泛的基板有效.
- 从反应添加物中顺地制备出度纯的三角氨基酸.
结论:
- 已经建立了一种新且高效的直接非对称的维尼洛格斯曼尼赫反应.
- 一种简单的性双功能氨酸-三级氨酸器官催化剂对于这种转化是有效的.
- 这种方法提供了一条简单的途径,以致于获得酶丰富的三角氨基酸,这是药物化学中有价值的构建模块.
相关概念视频
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