有机催化不对称的循环β-ketoesters的直接alpha-alkynylation循环β-ketoesters的组织催化不对称
Thomas B Poulsen1, Luca Bernardi, José Aleman
1Department of Chemistry, Center for Catalysis, Danish National Research Foundation, Aarhus University, DK-8000 Aarhus C, Denmark.
Journal of the American Chemical Society
|January 11, 2007
概括
这项研究引入了第一个使用奇拉相转移催化剂的β-ketoester和3-acyl oxindoles的有机催化酶选择性直接alpha-alkynylation. 该方法实现了对各种基质的高产量和出色的酶选择性.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
背景情况:
- 碳化合物的直接α功能化在有机合成中至关重要.
- 酶选择性基化是一个重要的合成挑战.
研究的目的:
- 开发第一个有机催化对beta-ketoesters和3-acyl oxindoles进行异位选择性直接alpha-alkynylation.
- 探索这种新奇反应的范围和机制.
主要方法:
- 利用性相转移催化剂来调解核性乙替代.
- 采用活性β--基因作为化试剂.
- 通过X射线分析对催化剂-基质中间体进行表征.
主要成果:
- 在一系列β-ketoesters和3-acyl oxindoles中实现了高产率 (74-99%) 和优异的酶选择活性 (88-97% ee).
- 证明了对乙烯基单元的立体控制的附着和对光学活性1,4-enynes的合成.
- 提出了一种催化中间模型来解释观察到的反选择性.
结论:
- 建立了一种新且高效的对抗选择性α-alkynylation的方法.
- 开发的方法提供了广泛的基板范围和高立体控制.
- 机理学见解为进一步进步非对称催化剂提供了基础.
相关概念视频
α-Alkylation of Ketones via Enolate Ions
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the strong interaction...
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.
Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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...
Aldol Condensation with β-Diesters: Knoevenagel Condensation
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
Preparation of Aldehydes and Ketones from Alcohols, Alkenes, and Alkynes
Aldehydes and ketones are prepared from alcohols, alkenes, and alkynes via different reaction pathways. Alcohols are the most commonly used substrates for synthesizing aldehydes and ketones. The conversion of alcohol to aldehyde, which involves the oxidation process, depends on the class of the alcohol used and the strength of the oxidizing agent. For instance, primary alcohol will form an aldehyde when treated with a weak oxidizing agent; however, it gets over-oxidized to a carboxylic acid in...


