化物选择性瓦克尔氧化法他胺保护的氨酸胺:一种新的催化路径到β3-氨基酸
Barbara Weiner1, Alejandro Baeza, Thomas Jerphagnon
1Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Journal of the American Chemical Society
|July 9, 2009
概括
一种新的瓦克尔氧化方法从氨酸中合成β-α-氨基酸前体. 这种高效的工艺产生了大量的化物,使得各种β-氨基酸和酒精合成成为可能.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 催化剂是一种催化剂.
背景情况:
- β 3 氨基酸是药物化学和科学中至关重要的构建基.
- 现有的β-α-氨基酸合成路径通常涉及多个步骤和有限的基质范围.
- 开发有效和多用途的方法来合成β-α-氨基酸是非常可取的.
研究的目的:
- 提出一种新的,高效的方法来合成β-α-氨基酸.
- 探索使用瓦克尔氧化方法来选择性合成阿尔代中间体.
- 建立一个多功能平台,用于随后合成β-氨基酸和酒精.
主要方法:
- 使用瓦克尔条件,氧化甲胺保护的氨胺.
- 使用互补的和铜催化剂系统 (例如,PdCl(2) /CuCl或Pd(MeCN) ((2)Cl(NO(2)) /CuCl(2)).
- 随后的氧化或减少所产生的化物,其次是去保护.
主要成果:
- 选择性氧化氨酸胺到化在优秀的产量.
- 对瓦克尔氧化反应的广泛基质范围的演示.
- 成功合成各种β-氨基酸和β-氨基醇.
结论:
- 开发的瓦克尔氧化方法提供了一种高效和多功能途径,可获得β-α-氨基酸前体.
- 这种方法在合成有价值的β-氨基酸衍生物方面取得了重大进展.
- 该方法的广泛适用性使其成为有机合成和药物发现的宝贵工具.
相关概念视频
Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The Wittig reaction, which converts aldehydes or ketones to alkenes using phosphorus ylides, proceeds through a nucleophilic addition‒elimination process.
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
Preparation of 1° Amines: Gabriel Synthesis
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Aldehydes and Ketones to Alkenes: Wittig Reaction Overview
The Wittig reaction is the conversion of carbonyl compounds-aldehydes and ketones-to alkenes using phosphorus ylides, or the Wittig reagent. The reaction was pioneered by Prof. Georg Wittig, for which he was awarded the Nobel Prize in Chemistry.
Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...
The carbonyl center is activated by...
Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...


