通过铜催化连续的索诺加希拉合和氨基循环化合成化骨
Heng He1, Jian-Quan Liu1, Xiang-Shan Wang1
1School of Chemistry and Materials Science, Jiangsu Key Laboratory of Green Synthesis for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, China. liujq316@jsnu.edu.cn.
Organic & biomolecular chemistry
|September 25, 2023
概括
这项研究提出了一种新的铜催化方法,用于合成胺融合化合物. 这种高效的协议为各种分子结构提供了一个模块化的方法,具有广泛的适用性.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 药用化学 医学化学
背景情况:
- 胺衍生物是药物化学中的重要支架.
- 有效的合成途径,使新的化皮里米丁系统非常受欢迎.
研究的目的:
- 开发一种新的,高效的,模块化合成策略,用于pyrimidine融合骨.
- 探索一种铜催化级联反应,涉及索诺加希拉合和氨基循环.
主要方法:
- 采用了一种铜催化反应序列.
- 关键步骤包括索诺加希拉合和5个外位数氨基循环.
- 作为起始材料,使用了一种2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - .
主要成果:
- 该协议有效地合成了多种类型的胺融合骨.
- 反应表明了广泛的基质范围和卓越的功能组兼容性.
- 酸性条件导致了 (Z) 产物的立体选择性异构化到 (E) 异构体.
结论:
- 建立了一个控制和模块化合成方法,用于pyrimidine-fused化合物.
- 开发的方法提供了高效率和功能组耐受性.
- 在酸性条件下的立体选择性转化为 (E) 异构体扩大了合成效用.
相关概念视频
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
3.0K
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the...
3.0K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
3.5K
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
3.5K
Preparation of 1° Amines: Azide Synthesis
4.0K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
4.0K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.2K
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.2K
Cycloaddition Reactions: Overview
2.6K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
2.6K
Preparation of 1° Amines: Gabriel Synthesis
3.6K
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...
3.6K


