通过水合甲基化合成四等碳中心的合成
1Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Journal of the American Chemical Society
|August 7, 2010
概括
这项研究引入了一种新的水合甲基化方法,用于创建复杂的四等碳中心. 一个独特的指导小组策略使得在温和条件下高选择性高效合成.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 合成方法论 合成方法论
背景情况:
- 四等碳中心是许多药品和天然产品中关键的结构动图.
- 这些中心的高效和选择性合成仍然是有机化学的一个重大挑战.
- 甲基化是一种强大的碳-碳键形成反应,但其用于构建四元中心的应用有限.
研究的目的:
- 开发一种用于合成四等碳中心的新型水合甲基化策略.
- 使用催化导向组来提高反应效率和选择性.
- 为了证明这种新合成方法的广泛适用性.
主要方法:
- 在甲基化反应中应用一种新型指导组 (基 1) .
- 定向组对基质和催化剂的共价和可逆结合.
- 反应条件的优化,包括温度和催化剂负载.
主要成果:
- 通过甲基化成功合成了高度替代的四级碳中心.
- 指导小组的策略显著加快了反应速度.
- 在温和的条件下 (35-55°C) 实现了优异的区域选择性 (分支:线性比> 94:6).
结论:
- 开发的水合甲基化方法为四级碳中心提供了一条有效的途径.
- 分子内定向小组策略是实现高反应性和选择性的关键.
- 这种方法在有机化学中为复杂分子合成提供了有价值的工具.
相关概念视频
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
01:28Multiple Halogenation of Methyl Ketones: Haloform Reaction
A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with the deprotonation of α hydrogen to form an enolate ion which reacts with the electrophilic halogen to give an α-halo ketone. The step continues until all the α protons are substituted to form a trihalomethyl ketone. The resulting molecule is unstable, and in the presence of a hydroxide base, it readily undergoes nucleophilic acyl substitution.
01:32Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
02:15Preparation of Alcohols via Addition Reactions
Overview
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...