1,5-不对称的诱导在介导的β-基甲基 aldol添加反应中的1,5-不对称的诱导
David A Evans1, Bernard Côté, Paul J Coleman
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Evans@chemistry.harvard.edu
Journal of the American Chemical Society
|September 4, 2003
概括
来自β-基甲基的乙烯酸盐实现了二分体选择性阿尔多尔添加,产生1,5-抗二醇. 反应条件允许通过酸盐或化物成分对立体化学进行控制.
科学领域:
- 有机化学 有机化学
- 立体选择性合成 立体选择性合成
背景情况:
- 阿尔多尔添加反应是有机合成中形成碳-碳键的基础.
- 控制阿尔多尔反应中的立体化学对于合成复杂分子,特别是药品至关重要.
研究的目的:
- 为了研究由β-alkoxy甲基基衍生乙酸盐的二选择性阿尔多尔添加.
- 探索方法来控制绝对立体化学在阿尔多尔反应涉及性β-基化.
- 为了阐明替代剂在 aldol 添加过程中对面部选择性的影响.
主要方法:
- 使用β-基甲基基衍生的乙烯酸盐添加阿尔多尔.
- 在双重立体差异化反应中使用奇拉性β-基化物.
- 调查易斯酸催化埃诺西兰添加剂.
主要成果:
- 甲基基衍生的β-基甲基乙烯酸盐始终具有1,5-抗二醇关系.
- 立体化学结果在各种类类似物和合物伙伴中是普遍的.
- 反应条件允许通过酸盐 (1,5-诱导) 或化物 (1,3-诱导) 组成部分选择性控制立体化学.
结论:
- 乙烯酸盐提供主导的1,5-抗诱导,占主导地位的化物影响.
- 易斯酸催化埃诺西兰添加有利于从化物中引入1,3-.
- 这项工作为立体控制的 aldol 添加提供了多功能策略.
相关概念视频
01:08Base-Catalyzed Aldol Addition Reaction
As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy carbonyl compound.
00:56Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction
The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.
01:10C–C Bond Formation: Aldol Condensation Overview
Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon–carbon bond under basic or acidic conditions. The aldol condensation reaction presented in Figure 1 constitutes an aldol addition reaction followed by the dehydration process.
01:15Acid-Catalyzed Aldol Addition Reaction
The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.
00:57C–C Bond Cleavage: Retro-Aldol Reaction
The reverse of the aldol addition reaction is called the retro-aldol reaction. Here, the carbon–carbon bond in the aldol product is cleaved under acidic or basic conditions to form two molecules of carbonyl compounds. The mechanism of the reaction consists of three steps.
In the first step, as depicted in Figure 1, the base deprotonates the β-hydroxy ketone at the hydroxyl group to form an alkoxide ion.
In the first step, as depicted in Figure 1, the base deprotonates the β-hydroxy ketone at the hydroxyl group to form an alkoxide ion.
01:33Aldol Condensation vs Claisen Condensation
Aldol condensation is an acid or base-catalyzed condensation between aldehydes or ketones to give an α,ꞵ-unsaturated carbonyl compound. A base-promoted condensation between ester molecules to produce a ꞵ-ketoester is known as the Claisen condensation. In the presence of a base, both reactions involve deprotonation of the acidic α hydrogen to produce the corresponding enolates. The nucleophilic enolates attack their respective nonenolized carbonyl compound forming a tetrahedral intermediate.