六甲基伊尔迪西拉齐德介导的乙烯化:三乙烯胺对E/Z选择性和乙烯酸盐反应性的影响
Peter F Godenschwager1, David B Collum
1Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
Journal of the American Chemical Society
|June 19, 2008
概括
在三乙烯/多中,六甲基二甲基化物 (LiHMDS) 快速以高选择性对和质进行乙醇化. 氨基化酸盐增强了阿尔多尔和爱尔兰-克莱森反应,显示出改善的二选择性和加速的重新排列.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
背景情况:
- 六甲基西拉化物 (LiHMDS) 是一种在有机合成中广泛使用的强型非核基.
- 溶剂效应显著影响有机金属试剂的反应性和选择性.
研究的目的:
- 为了研究使用LiHMDS在三乙烯胺 (Et3N) /多中对非环基和的乙醇化.
- 探索涉及Et3N溶解乙烯酸盐的反应的机械路径和立体化学结果.
- 将反应性和选择性与THF等传统溶剂系统进行比较.
主要方法:
- 在Et3N/toluene中使用LiHMDS进行和 Ester的化.
- 使用光谱和运动分析的机械学研究.
- 对阿尔多尔凝结和爱尔兰-克莱森重组产物的立体化学分析.
主要成果:
- 实现了具有高E/Z选择性的非循环和的快速化.
- 机理学研究支持Et3N.中LiHMDS的二元基机制.
- 与THF化酸盐相比,Et3N化酸盐在阿尔多尔和爱尔兰-克莱森反应中表现出增强的二选择性.
- 观察到爱尔兰-克莱森重组的加速是20倍,有自催化作用的证据.
结论:
- 在Et3N/toluene中的LiHMDS提供了一种高度选择性和高效的方法来产生酸盐.
- 氨基化乙烯酸盐在反应性和对后续转换的立体控制方面具有明显的优势.
- 这些发现强调了氨基溶解在有机金属化学和反应优化中的重要性.
相关概念视频
01:33Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
02:43E2 Reaction: Stereochemistry and Regiochemistry
Elimination reactions of alkyl halides can yield one or more alkenes depending on the specific regiochemical and stereochemical considerations. While the regiochemistry of the reaction governs the location of the double bond in the product, the stereochemical requirements often influence the geometry.
When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major product and...
When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major product and...
01:12Stereochemical Effects of Enolization
The chiral α-carbon of the carbonyl compound is the stereocenter of the molecule. As shown in the figure below, when such a carbonyl compound undergoes racemization under an acidic or basic condition, an achiral enol is formed.
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...
02:43E1 Reaction: Stereochemistry and Regiochemistry
One of the critical aspects of the E1 reaction mechanism, as also observed in E2, is the regiochemistry, with multiple regioisomers obtained as products. In the example discussed, the presence of water as a weak base favors elimination over substitution to generate two alkenes. Given that alkenes’ stability increases with the number of alkyl groups across the double bond, typically, E1 reactions lead to the Zaitsev product, for this is more substituted and stable than the Hofmann product.
01:18Reactivity of Enols
Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is governed by factors like...