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Asymmetric reaction by means of movel high activation of aza-aromatics

氮杂芳香族化合物的Movel高活化不对称反应

基本信息

批准号：
10650832
负责人：
YAMAGUCHI Ryohei
金额：
$ 2.05万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10650832/
关键词：
Asymmetric Reaction Aza-aromatics Allylsilane Quinolinium Ion Isoquinolinium Ion

项目摘要

Development of methodology for stereoselective introduction of useful carbon substituents into nitrogen heterocycles is of great importance for synthesis of various physiologically and pharmacologically active nitrogen heterocyclic cmopounds. One of the methodology comprises addition reactions of various carbon nucleophiles to activated aza-aromatics and has been extensively investigated. All of them reported so far, however, have exploited diastereoselctive additions of achiral organometallic reagents to aza-aromatics bearing a chiral auxiliary in an activating group or on the aromatic ring. There has been no highly enantioselective addition reaction of a chiral organometallic reagent to achiral aza-aromatics.We have found that highly activated N-acylated aza-aromatic ions can be generated when aza-aromatics such as us isoquinoline and qinoline are treated with phenyl chloroformate and silver triflate and that N-acylated aza-aromatic ions thus produced can readily react with allylsilanes and alkynylsilanes.On the basis of the above results, we have found in the present study that the addition reactions of a chiral allylsiane to highly activated N-acylated aza-aromatic ions proceed in a highly enantioselective manner. To the best of our knowledge, this is the first example of a highly enantioselective addition reaction of a chiral organometallic reagent to an aza-aromatic.A variety of functional groups, such as ester, bromo, formyl, cyano, and nitro, on isoquinoline and quinoline are tolerated in the present asymmetric addition reactions with more than 90% enantioselectivity, showing the high chemoselectivty. The absolute configurations of the products are confirmed and it is supported that the reactions proceed via anti-periplanar anti-SE' mechanism.

氮杂环化合物立体选择性引入碳取代基的方法学研究对于合成具有生理活性和生物活性的氮杂环化合物具有重要意义。其中一种方法包括各种碳亲核试剂与活性氮杂芳烃的加成反应，并已被广泛研究。然而，迄今为止报道的所有这些都利用了非手性有机金属试剂对在活化基团或芳环上带有手性助剂的氮杂芳族化合物的非对映选择性加成。手性有机金属试剂与非手性氮杂芳烃没有高对映选择性的加成反应，我们发现，用氯甲酸苯酯和三氟甲磺酸银处理氮杂芳烃如异喹啉和喹啉，可以生成高活性的N-酰化氮杂芳烃离子，这样生成的N-酰化氮杂芳烃离子很容易与烯丙基硅烷和炔基硅烷反应。我们在本研究中发现，手性烯丙基硅烷与高度活化的N-酰化氮杂芳族离子的加成反应以高度对映选择性的方式进行。这是第一个手性有机金属试剂与氮杂芳香化合物进行高对映选择性加成反应的实例，该反应可容许异喹啉和喹啉上的酯基、溴基、甲酰基、氰基和硝基等多种官能团参与，对映选择性均大于90%，显示出较高的化学选择性.证实了产物的绝对构型，并支持反应是通过反包平面反SE '机理进行的。