已解决的奇拉性3,4-酸和它们在催化不对称基基化中的应用
Thomas P Clark1, Clark R Landis
1Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|September 25, 2003
概括
研究人员开发了用于催化应用的新型性素. 这些新型化合物在催化基化反应中表现出高的反选择性,显示出对不对称合成的希望.
科学领域:
- 有机化学 有机化学
- 不对称的催化剂.
- 有机化学化学 有机化学
背景情况:
- 化素是不对称催化中的关键配体,可合成化纯化合物.
- 为推进催化方法,开发高效的合成路径以获得新性氨酸联体是必不可少的.
- 帕拉催化基化是一种强大的碳-碳键形成工具,通常需要性配体来实现反选择性.
研究的目的:
- 为了合成一种新的类型的性素连接体.
- 为了研究这些连接体在催化不对称基化中的实用性.
- 探索连接体结构和反应条件对选择性的影响.
主要方法:
- 单凝结反应合成了血性素前体.
- 通过二聚体盐结晶的赛米混合物的溶解.
- 溶解后的氨酸与氨基酸和氨基酸的合,产生性联结物库.
- 帕拉催化不对称的基基化,使用合成的性素.
主要成果:
- 一种新的素,rac-N,N'-phthaloyl-2,3-(2-carboxyphenyl) -phenyl-3,4-diazaphospholane (rac-2),以88%的产量进行了合成.
- 通过分辨率和随后的衍生来获取奇拉尔素 (3).
- 在基酸的基化催化过程中,获得了高选择性 (高达97% ee).
- 观察到对氨基酸替代剂和PF6-盐的存在具有显著的酶选择性敏感性.
结论:
- 建立了一种新且高效的方法来合成多种性素连接体.
- 合成的性素是催化非对称性基化酶的有效连接体.
- 配体设计,特别是氨基酸附属物和反附属物,在实现高反选择性方面发挥着至关重要的作用.
相关概念视频
01:01Acid 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...
01:12Acid Halides to Esters: Alcoholysis
Alcoholysis is a nucleophilic acyl substitution reaction in which an alcohol functions as a nucleophile. Acid halides react with alcohol to produce esters. The mechanism proceeds in three steps:
01:07Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
01:19Acid Halides to Alcohols: LiAlH4 Reduction
Acid halides are reduced to alcohols in the presence of a strong reducing agent like lithium aluminum hydride.
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
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...
01:10Factors Affecting α-Alkylation of Ketones: Choice of Base
α-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed by nucleophilic substitution. The choice of base employed is essential as it is the key factor in determining the reaction outcome.
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence, side reactions...
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence, side reactions...