通过有机催化剂[12 + 2]循环添加物构建Cycl[3.2.2]azine核心
Nicolaj Inunnguaq Jessen1, Giulio Bertuzzi1, Maksimilian Bura1
1Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Journal of the American Chemical Society
|April 19, 2021
概括
一种新型的[12 + 2]循环添加反应使用器官催化产生了性循环[3.2.2]azine核心. 这一单步过程为复杂分子合成提供了高立体选择性.
科学领域:
- 有机化学
- 不对称的合成
- 催化剂
背景情况:
- 在药物化学中构建复杂的性支架至关重要.
- 开发高效和立体选择性的循环加法反应是一个持续的挑战.
- 奇拉环[3.2.2]亚核是有价值的,但在合成上具有挑战性的图案.
研究的目的:
- 开发第一个可选择性[12 + 2]循环添加,用于构建奇拉性循环[3.2.2]azine核心.
- 通过氨基催化剂来研究机制并优化立体选择性.
- 探索新开发的循环添加反应的范围和效用.
主要方法:
- 有机催化的一步[12 + 2]循环添加反应.
- 使用5H-[a]pyrrolizine-3-carbaldehydes和缺电子的2π组件进行氨基催化.
- 结合实验和计算调查以阐明反应机制和立体选择性.
- 对各种缺电子2π组件的不同氨基催化剂的应用.
主要成果:
- 首次成功开发用于奇拉性cyc[3.2.2]azine合成的选择性[12 + 2]循环添加.
- 在目标支架上获得良好的产量.
- 证明对多种替代物模式的稳定性以及对各种2π组件的扩展范围.
- 确定了一个阶段性机制,关键的环闭步骤是立体化学结果.
结论:
- 开发的有机催化[12 + 2]循环添加提供了一个有效的途径,以奇拉循环[3.2.2]azine衍生物.
- 反应机制涉及氨基催化剂的双激活,解释了高度的立体选择性.
- 该方法是多功能且适用于各种基质,产生具有潜在光物理性质的化合物.
更多相关视频
相关概念视频
01:16Cycloaddition Reactions: Overview
3.0K
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.
3.0K
![[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12417.jpg&w=3840&q=75)
01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
11.2K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
11.2K
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
3.9K
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
3.9K
01:12Cycloaddition Reactions: MO Requirements for Photochemical Activation
2.3K
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.
2.3K
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
2.5K
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).
2.5K
01:17Thermal Electrocyclic Reactions: Stereochemistry
2.2K
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
2.2K