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

在氮杂环中立体选择性引入有用碳取代基的方法的发展对于合成各种具有生理和药理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化的氮杂芳烃的加成反应，并已被广泛研究。然而，到目前为止，所有的报道都是利用非手性有机金属试剂的非对映选择性加成到在活化基团或芳环上具有手性助剂的氮杂芳香化合物上。手性有机金属试剂对非手性氮杂芳烃的加成反应尚无高度的对映选择性。我们发现，用氯甲酸苯酯和三酸银处理偶氮芳香族化合物（如异喹啉和喹啉）可以生成高度活化的n -酰化偶氮芳香族离子，并且由此产生的n -酰化偶氮芳香族离子很容易与烯丙基硅烷和炔基硅烷反应。基于以上结果，本研究发现手性烯丙基烷与高度活化的n -酰化氮杂芳香离子的加成反应具有高度的对映选择性。据我们所知，这是手性有机金属试剂与氮杂芳香化合物高度对映选择性加成反应的第一个例子。在不对称加成反应中，异喹啉和喹啉上的酯、溴、甲酰基、氰基、硝基等多种官能团均能被耐受，对映选择性超过90%，显示出较高的化学选择性。证实了产物的绝对构型，并证实了反应是通过反周面反se机制进行的。

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.