不和O-基酸盐的分子内氧化:一种非常多功能的氧乳糖的入口
Duncan J Wardrop1, Edward G Bowen, Raymond E Forslund
1University of Illinois at Chicago, Department of Chemistry, 845 West Taylor Street, Room 4500, Chicago, Illinois 60607-7061, USA. wardropd@uic.edu
Journal of the American Chemical Society
|October 1, 2009
概括
一种新的多功能方法使用中介氧化制备五至八个成员的酸乳酸. 这种立体特异性和区域选择性转换为复杂的循环胺合成提供了一个新的合成途径.
科学领域:
- 有机化学 有机化学
- 合成方法论 合成方法论
- 药用化学 医学化学
背景情况:
- 乳酸盐是许多药品中发现的至关重要的异环化合物.
- 有效合成中型乳酸 (五至八个环) 仍然是一个合成挑战.
- 开发新的循环化策略对于获得多样化的乳支架至关重要.
研究的目的:
- 开发一种多功能和高效的方法来合成五至八个成员的氧乳酸盐.
- 探索一种新的 (III) 介导的氧化化反应,用于乳的形成.
- 为了研究这种新合成转化的立体化学和区域化学结果.
主要方法:
- 使用 (III) 介导的不和O-基酸盐的氧化.
- 研究了反应机制,提出单片和双循环N--N-氧化离子中间体.
- 在22种不同的基质上检查了反应的立体特异性和区域选择性.
主要成果:
- 成功制备了一系列五至八个成员的氧乳糖.
- 证明了 (III) 中介氧化化方法的多功能性.
- 在大多数测试病例中观察到高立体特异性和区域选择性,表明可预测的反应结果.
- 提供了对拟议的中间体的机制性见解.
结论:
- 开发的(III) 介导的氧化化是一种强大而通用的酸乳合成方法.
- 这种方法提供了一个立体特异性和高度区域选择性的途径,以获得有价值的五至八个成员的乳结构.
- 这些发现为获得与药物发现相关的复杂异环化合物的新合成策略做出了贡献.
相关概念视频
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
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.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...