速率限制步骤在原型的氨酸催化分子内醇反应中C-C键形成之前
Hui Zhu1, Fernando R Clemente, K N Houk
1University of California, Merced, School of Natural Sciences, P.O. Box 2039, Merced, California 95344, USA.
Journal of the American Chemical Society
|February 5, 2009
概括
研究了Hajos-Parrish-Eder-Sauer-Wiechert反应,这是类催化的一个模型. 在这个关键的有机反应中,碳-碳键的形成并不是限制速度的步骤.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 反应机制 反应机制
背景情况:
- 哈约斯 - 帕里什 - 埃德 - 索尔 - 维赫特反应是林催化分子内醇反应的基本例子.
- 烯催化反应是有机合成中快速扩大的领域.
- 了解这些反应的机制对于开发新的合成方法至关重要.
研究的目的:
- 调查哈约斯-帕里什-埃德-索尔-维赫特反应中的速度限制步骤.
- 提供关于proline-catalyzed aldol反应的机制的最终实验证据.
主要方法:
- 使用了对 (13) C 动态同位素效应的实验测量.
- 在有机化学中应用已确定的技术来阐明机理学.
主要成果:
- 确切地证明,碳-碳键的形成不是限制速度的步骤.
- 提供了支持修订机制理解的定量数据.
结论:
- 这些发现挑战了以前关于这种原型反应中速度决定步骤的假设.
- 提供了对普罗林催化转换的更广泛类别的关键见解.
相关概念视频
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.
01:08Base-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.
00:57C–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.
01:15Acid-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.
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.
01:18Intramolecular Aldol Reaction
Intramolecular aldol reaction occurs in dicarbonyl compounds such as dialdehydes, diketones, and keto-aldehydes. The dicarbonyl compounds possess more than one nucleophilic ⍺ carbon for the base to deprotonate and form the enolates. For example, in symmetrical diketones, there are four ⍺ carbons. Hence, four types of enolates are possible when treated with a base. However, since the molecule is symmetrical, the enolates formed on either side of one carbonyl group are equivalent to those formed...