在C2-对称的循环催化酶选择性氨酸环化过程中
Feng Chen1, Chong Kiat Tan, Ying-Yeung Yeung
1Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543.
Journal of the American Chemical Society
|January 15, 2013
概括
这项研究引入了一种新型的催化不对称循环化方法,用于从氨酸胺基中制造性罗利丁. 这些pyrrolidines可以转化为高度丰富的piperidines,展示了一个新的合成途径.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
- 合成方法论 合成方法论
背景情况:
- 在药物化学中,开发高效的合成复杂含异环的方法至关重要.
- 非对称催化提供了一种强大的方法来控制有机合成中的立体化学.
研究的目的:
- 报告一种新型的催化不对称的三替代胺胺的环化.
- 开发一种固态选择性合成的酶丰富的pyrrolidine和piperidine衍生物.
主要方法:
- 使用C(2) -对称的曼尼托尔衍生的循环催化剂.
- 采用N-甲胺作为化剂.
- 研究了罗利丁产品的重新排列到piperidines的情况.
主要成果:
- 实现了三位置换的氨基胺的催化不对称环化.
- 产生具有两个立体中心的增抗丰富型罗利丁产品.
- 证明了对2,3-非替代型皮佩里丁的重新排列,具有较高的二聚体选择性和方位特异性.
结论:
- 开发的方法提供了有效的获取有价值的性pyrrolidines和piperidines.
- 催化系统为异环的立体控制合成提供了一个新的策略.
- 重组的高enantiospecificity是这种转换的一个关键特征.
相关概念视频
Halogenation 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.
Formation of Halohydrin from Alkenes
An alkene, such as propene, reacts with bromine in the presence of water to yield a halohydrin. Halohydrins contain a halogen and a hydroxyl group attached to adjacent carbons. When the halogen is bromine, it is called a bromohydrin, while a chlorohydrin has chlorine as the halogen.
Radical Substitution: Allylic Bromination
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
SN2 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.
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
Radical 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.


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