剖析一个催化不对称的chlorolactonization的立体控制元件:同添加避免了桥梁
Roozbeh Yousefi1, Kumar Dilip Ashtekar, Daniel C Whitehead
1Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
Journal of the American Chemical Society
|September 13, 2013
概括
这项研究揭示了选性化的立体化学,显示了对新形成的立体中心的独立控制. 这些发现表明了一种阶段性机制,与典型的桥梁离子中间体不同.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 立体化学是一种立体化学.
背景情况:
- 酵素选择性化是有机合成中的一个关键反应.
- 了解立体化学结果对于控制分子结构至关重要.
- 之前的模型经常通过桥接中间体假定协同的反添加.
研究的目的:
- 为了阐明在对抗选择性醇脱氧化中添加的绝对和相对立体化学.
- 为了研究4--4-丁酸衍生物的chlorolactonization的机制.
- 挑战离子桥梁的普遍模式.
主要方法:
- 通过 (DHQD) 2PHAL.催化而发生的酶选择性化.
- 使用同位素标记分析立体化学结果.
- 通过核磁共振 (NMR) 光谱学和衍生研究对产品进行表征.
主要成果:
- 观察到主要的离子和核的合成添加.
- 这两个新形成的立体中心是独立设置的.
- 立体化学结果受到不同的因素的影响,这表明非桥梁中间体.
结论:
- 观察到的立体化学支持一个阶段性机制为chlorolactonization.
- 一个非桥接中间体允许对立体中心进行独立控制.
- 这挑战了在类似反应中离子桥接的传统观点.
相关概念视频
02:46Halogenation of Alkenes
Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
02:23SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.