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

在氮杂环上引入有用的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。本文研究了β-取代缺电子烯丙基锡试剂与酰氯活化的氮杂环的反应，并发展了一种高选择性地将Michael受体引入杂环的方法，发现缺电子烯丙基锡试剂与4-酰基吡啶的反应以区域选择性的1，4-加成方式进行，得到多官能化的4，4-二取代1，4-二氢吡啶与正常烯丙基锡试剂的反应中观察到的1，2-加成形成对比。用半经验分子轨道方法计算了缺电子锡试剂与4-氰基吡啶、3-取代吡啶和3，5-二甲氧羰基吡啶的电子密度和前线分子轨道，解释了缺电子锡试剂与4-取代吡啶的区域选择性1，4-加成的原因。在缺电子烯丙基锡试剂与4-酰基吡啶的反应中观察到4-加成。计算结果表明，实际的HSAB原理不能解释上述1，4-区域选择性，中间体中缺电子碳正离子与4-酰基之间的稳定作用可能起重要作用。用同样的方法将Michael受体引入异喹啉和β-咔啉体系中，合成了多环α-亚甲基-γ-已经实现了内酰胺。

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.