胺基与化物具有高度反选择性的催化性阿尔多尔反应
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO, Japan Science Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|July 6, 2006
概括
氧化催化了胺和化物之间的直接阿尔多尔反应,实现了高的抗选择性. 这种方法在温和条件下与各种类甲基一起工作,有效地产生所需的产品.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 合成方法论 合成方法论
背景情况:
- 阿尔多尔反应是有机合成中基本的碳-碳键形成反应.
- 与传统方法相比,胺的直接阿尔多尔反应提供了一种简化方法.
- 开发高度选择性和高效的催化系统仍然是一个关键的挑战.
研究的目的:
- 开发一种新的氧化催化直接阿尔多尔反应的胺与化物.
- 为了在温和的反应条件下实现高抗选择性和产量.
- 探索开发的催化系统的范围和局限性.
主要方法:
- 利用氧化作为直接阿尔多尔反应的催化剂.
- 使用略微多余的胺来促进反应的顺利进展.
- 研究了与多种芳香,异环和α,β-不和化物反应的反应.
主要成果:
- 成功开发了一种高度反选择性的胺与化物直接阿尔多尔反应.
- 实现了高产量和优秀的抗选择性对于所需的阿尔多尔添加物.
- 已证明适用于广泛的化物基质.
- 报告了一种使用奇拉性配体的催化酶选择性变体.
结论:
- 氧化是胺的直接阿尔多尔反应的有效催化剂.
- 开发的方法提供了一个简单而有效的途径,以抗选择性阿尔多尔产品.
- 催化酶选择方法扩大了这种反应的合成效用.
相关概念视频
01:13Relative Reactivity of Carboxylic Acid Derivatives
Carboxylic acid derivatives such as acid halides, anhydrides, esters, and amides undergo nucleophilic acyl substitution reactions with varying degrees of reactivity.
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
01:12Acid Halides to Esters: Alcoholysis
Alcoholysis is a nucleophilic acyl substitution reaction in which an alcohol functions as a nucleophile. Acid halides react with alcohol to produce esters. The mechanism proceeds in three steps:
01:19Reactions of Acid Anhydrides
The reactions of acid anhydrides are analogous to the reactions of acid chlorides and proceed via a nucleophilic acyl substitution. They only differ in the identity of the leaving group. During an acid chloride reaction, the leaving group is a chloride ion, and the by-product is hydrochloric acid. However, in an acid anhydride reaction, the leaving group is a carboxylate ion, and the by-product is a carboxylic acid.
01:21Acid-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...
01:15Acid Halides to Alcohols: Grignard Reaction
Organomagnesium halides, commonly known as Grignard reagents, convert acid halides to tertiary alcohols. The reaction requires two equivalents of the Grignard reagent and proceeds via a ketone intermediate.
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs,...
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs,...
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.