通过催化的酸盐酸盐化,通过化的化
Diem H T Phan1, Byoungmoo Kim, Vy M Dong
1Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Journal of the American Chemical Society
|October 10, 2009
概括
研究人员开发了一种新的原子经济方法,用于使用enantioselective ketone hydroacylation合成phthalides. 这种方法产生具有高反选择性的化物产品,在有机合成中取得了显著的进步.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 催化剂是一种催化剂.
背景情况:
- 聚化物是具有重要的生物相关性的五个成员乳,在各种植物来源中自然存在.
- 现有的化物合成方法可能缺乏原子经济或高效的酶选择性控制.
研究的目的:
- 为了引入第一个原子经济方法用于甲合成.
- 通过分子内基水酸化,在化物生产中达到高的酶选择性.
- 为了研究 counterions 对催化性能的影响.
主要方法:
- 使用带有Duanphos连接体的催化剂,采用酶选择性分子内基水酸化.
- 使用各种2-二甲作为基质.
- 为复合体研究了不同的 counterions (NO3,OTf,OMs).
主要成果:
- 在甲产品方面取得了良好的产量.
- 证明了高的反抗选择性,范围从92%到98% ee.
- 确定了 counterions 在调节反应性和 enantioselectivity 中的关键作用.
- 成功地进行了 (S) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 的简洁的不对称的总合成.成功地进行了 (S) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 的简洁的不对称的总合成.
结论:
- 开发的酶选择性酸水酸化是一种高效且原子经济的化物生产途径.
- 对比选择对于优化催化过程至关重要.
- 这种方法提供了一个有价值的工具,用于获取含聚丰富的甲酸,包括天然产品.
相关概念视频
Acid-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...
Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The Wittig reaction, which converts aldehydes or ketones to alkenes using phosphorus ylides, proceeds through a nucleophilic addition‒elimination process.
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
Alkynes 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.
Preparation of Alkynes: Dehydrohalogenation
Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an α-hydroxy ketone product. The α-hydroxy ketone is also called acyloin, so the reaction is referred to as ‘acyloin condensation.’
Acid Halides to Carboxylic Acids: Hydrolysis
Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid...


