An Unique Reaction Selctivity of Electron Deficient Allylic Tin Reagonts and Synthesis of Multi Functionalized 1,4-Dihydropyridines

缺电子烯丙基锡试剂的独特反应选择性及多官能化1,4-二氢吡啶的合成

基本信息

批准号：
06651006
负责人：
YAMAGUCHI Ryohei
金额：
$ 0.26万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Development of methodology for introduction of useful functional carbon substituents into nitrogen heterocycles is of great importance for synthesis of various physiologically and pharmacologically active nitrogen heterocyclic compounds. We have studied reactions of beta-substituted electron deficient allylic tin reagents with nitrogen heterocycles activated by acyl chlorides and developed a highly selective method for introduction of those Michael acceptors to heterocycles.It has benn found that reactions of electron deficient allylic tin reagents with 4-acylpyridines proceed in a regioselective 1,4-addition manner to give multi functionalized 4,4-disubstitued 1,4-dihydropyridines in contrast with the 1,2-addition observed in the reactions of normal allylic tin reagents. On the other hand, the predominant 1,4-addition has not been observed in the reactions of electron deficient allylic tin reagents with 4-cyanopyridine, 3-substituted pyridines, or 3,5-dimethoxycarbonylpyridine.Electron densities and frontier molecular orbitals of various allylic tin reagents and 4-substituted pyridinium ions have been calculated by a semi-empirical molecular orbital method to clarify the reasons for the regioselective 1,4-addition observed specifically in the reactions of electron deficient allylic tin reagents with 4-acylpyridines. The calculations suggest that practical HSAB principle can not account for the above 1,4-regioselectivity and that some stabilizing interaction between the electron deficient carbocation and the 4-acyl group in the intermediate would make an important role.In addition, the Michael acceptors can be introduced into isoquinoline and beta-carboline systems by the same method as above and a new synthesis of polycyclic alpha-methlene-gamma-lactams has been achieved.

将有用的功能性碳取代基引入氮杂环的方法对于合成各种生理和药理活性氮异质化合物至关重要。我们已经研究了β-基建造的电子缺乏烯丙基锡试剂与酰基氯化物激活的氮杂环的反应，并开发了一种高度选择性的方法来引入这些迈克尔受体对异性生物的引入。功能化的4,4-脱卵形1,4-二氢吡啶与在正常烯丙基烯丙基TIN试剂的反应中观察到的1,2个结合相反。另一方面，在电子缺乏酸酸的锡试剂的反应中尚未观察到主要的1,4个结构，与4-氰基吡啶，3-溶解的吡啶或3,5-二甲氧基甲氧基吡啶二吡啶的反应。已经通过半经验的分子轨道方法计算得出，以阐明在电子缺乏烯丙基烯丙基TIN试剂与4-酰基吡啶的反应中特别观察到的区域性选择性1,4增添的原因。计算表明，实用的HSAB原理无法说明上述1,4不良选择性，并且中间体中电子缺乏的碳分配与4-酰基群之间的某些稳定相互作用将发挥重要作用。在同一方法中，可以将迈克尔受体引入等二喹啉和beta-carboline Systems，以及上述新的方法，以及POTYCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCOCCCCY and e new poloty new poloty conticess and poloty consessiss new Synsiss of poloty consessis已经实现了α-甲氧乙烯 - 甲酰胺酰胺。