有机催化不对称的合添加到艾伦酸和酸
Petteri Elsner1, Luca Bernardi, Giorgio Dela Salla
1Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Journal of the American Chemical Society
|March 18, 2008
概括
这项研究引入了使用奇拉四等盐的有机催化式enantioselective结合加法反应. 这些反应有效地从循环β-ketoesters和glycine imines中产生奇拉ββ,玛不和碳基化合物和α-氨基酸衍生物.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
- 机体催化剂是有机催化剂.
背景情况:
- 结合物添加反应对于碳-碳键的形成至关重要.
- 开发复杂分子合成的enantioselective方法仍然是一个挑战.
研究的目的:
- 报告第一个循环β-ketoesters和glycine imines的有机催化式enantioselective结合添加到电子缺乏的allenes.
- 建立有效的催化系统,以生产性不和碳烯化合物和氨基酸衍生物.
主要方法:
- 阶段转移催化使用基基或双基的奇拉四级盐.
- 用各种循环β-ketoesters和glycine imine衍生物进行反应优化和范围探索.
主要成果:
- 单独形成具有高产量和优良的 (90-96% ee) 酶选择性 (enantioselectivities) 的奇拉ββ,玛不和碳烯化合物.
- 顺利的不对称的合添加甘氨酸胺,产生光学活性的α-氨基酸衍生物 (60-88% ee).
- 通过转化成六二二子和替代性酸盐的合成实用性的证明.
结论:
- 开发了一种新型的有机催化酶选择性结合添加剂,用于缺电子的基.
- 建立了一种通用的方法来获取有价值的性构建块.
- 突出了在进一步的化学转化过程中生成的奇拉产品的合成潜力.
相关概念视频
01:09Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α,β-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in the molecule leads to three resonance structures. The hybrid form exhibits two probable electrophilic sites: the carbonyl carbon and the β carbon.
01:08Conjugate Addition of Enolates: Michael Addition
The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.
01:10α-Alkylation of Ketones via Enolate Ions
Ketones with α protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the α carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the α carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the strong interaction...
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.
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
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).
01:08Base-Catalyzed Aldol Addition Reaction
As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a β-hydroxy carbonyl compound.