角替代的1-azabicyclic环系统的选合成:使用aza-Cope重排的动态动态分辨率
Tatsuya Ito1, Larry E Overman, Jocelyn Wang
1Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II, Irvine, California 92697-2025, USA.
Journal of the American Chemical Society
|February 24, 2010
概括
一种新型的酶选择性合成提供了角度替代的1-azabicyclic amines,具有高产率和99%的酶因子过量 (ee). 这种方法利用独特的动态动力学分辨率策略来实现高效的立体选择合成.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 立体化学是一种立体化学.
背景情况:
- 1-阿扎比环分子是药物化学中的重要支架.
- 开发高效的酶选择性合成路径对于获得纯立体异构体至关重要.
研究的目的:
- 报告一个新的对角替代的1-azabicyclic分子的enantioselective合成.
- 为了获得高产量和合成的双循环氨基酸中的反体过量 (ee).
主要方法:
- 在五个步骤中,从循环阿尔卡诺和纯 (R) -2--3-丁胺中组装起始材料.
- 应用一个涉及动态动态分辨率的级联转换.
- 结合了iminium离子的快速平衡与 diastereoselective sigmatropic重排的组合.
主要成果:
- 成功合成角替代的cis-octahydrocyclopenta[b]pyrroles,cis-octahydroindoles,cis-decahydrocyclohepta[b]pyrroles和cis-octahydrocyclopenta[b]pyridine在良好的产量和99% ee.
- 对于大多数自行车产品,CIS立体异构体的独占形成.
- 作为高EE的cis和trans立体异构体的混合物,生成十基诺林.
结论:
- 开发的酶选择合成为动态动力学分辨率提供了一个新的策略.
- 这种方法可以有效地获得有价值的立体化学定义的1-azabicyclic化合物.
- 该方法适用于一系列循环原料.
相关概念视频
[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement
The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
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In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
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Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position.
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Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...


