在无铜的点击化学中,二利拉扎环氧氨酸的活性
Chelsea G Gordon1, Joel L Mackey, John C Jewett
1Departments of Chemistry, University of California - Berkeley, 94720, United States.
Journal of the American Chemical Society
|May 5, 2012
概括
应变和电子显著影响无铜点击化学动力学. 基因结合角度的降低和基阻碍在比亚利拉扎环氧 (BARAC) 类似物中与反应性相关,使新的点击化学试剂的合理设计成为可能.
科学领域:
- 生物对等化学的化学.
- 化学动力学 化学动力学
- 有机合成 有机合成
背景情况:
- 无铜点击化学,cyclooctynes和azides之间的1,3-双极循环添加,对于生物发现至关重要.
- 了解反应动力学对于动态过程研究至关重要,特别是在体内.
研究的目的:
- 系统地分析应变和电子因素对循环丁酸反应动力学的影响.
- 为了调查biarylazacyclooctynone (BARAC) 和其类型的反应性.
- 为设计新型点击化学试剂建立结构-反应关系.
主要方法:
- 实验动力测量. 实验动力测量.
- 使用密度函数理论 (DFT) 扭曲/相互作用过渡状态模型的计算研究.
- 用于确定基结合角度的X射线晶体学.
主要成果:
- 巴拉克的环上的替代物通过电子或硬质效应影响过渡状态能量.
- 电子干扰对反应速率产生了适度的影响,而固态障碍显著减缓了反应.
- 在降低基因结合角度和增加循环基因反应性之间发现了相关性.
- 巴拉克的乳形状影响了化合物的反应性.
结论:
- 扭曲/相互作用模型和结合角度分析可以预测循环催化素的反应性.
- 这些发现有助于合理设计新的试剂,用于无铜点击化学.
- 优化硬体和电子性能是提高点击反应效率的关键.
相关概念视频
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
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 para position.
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
Cycloaddition Reactions: Overview
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.
Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism
Birch reduction uses solvated electrons as reducing agents. The reaction converts benzene to 1,4-cyclohexadiene. The reaction proceeds by the transfer of a single electron to the ring to form a benzene radical anion. This anion is highly basic—it abstracts a proton from the alcohol to form a cyclohexadienyl radical. Another single electron transfer gives the cyclohexadienyl anion. A proton transfer from the alcohol forms 1,4-cyclohexadiene. Since this reduction occurs via radical anion...


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