Studies on the Development of New Generation Method of Nitrogene Centered Radicals and their Application to Intermolecular Cycloaddition Reaction

本研究开发了用碘氮杂环丙烷类化合物生成各种氮杂高烯丙基自由基(2-烯基酰胺基)的方法及其在分子间[3+2]环加成反应中的应用。2004年的研究结果如下：1.不对称自由基[3+2]环加成反应合成光学活性八氢吲哚衍生物去年，我报道了利用光学活性双环碘氮杂环进行的不对称自由基[3+2]环加成反应。该反应产物有望成为多种天然八氢吲哚生物碱的有效合成中间体。然而，自由基反应通常不适用于天然产物的合成，因为随着反应的放大，化学产率通常会显著下降。2.碘甲基环丙烷衍生物与二烯和烯炔的自由基级联反应。关于目前使用的碘烷基化三元环化合物的反应，我报道了环上有两个电子的碘甲基环丙烷进行的碘原子转移自由基[3+2]环加成反应。也就是说，在三乙基硼烷存在下，碘甲基环丙烷通过与各种烯烃的碘原子转移环加成反应，有效地生成了烯丙化的活性亚甲基自由基，从而得到了产率和立体选择性都很好的环戊烷衍生物。在这一年里，我研究了进食和烯烃的激进级联反应。我发现，碘甲基环丙烷与1，4-二烯和1，4-烯炔反应，通过[3+2]环加成和随后的5-外环化，以很好的产率得到了双环[3.3.0]辛烷衍生物。

The present research is development of efficient generation method of various aza-homoallyl radical (2-alkenylated amidyl radicals) species using iodoaziridine derivatives and their application to intermolecular radical [3+2] cycloaddition reaction. The results in 2004 are as follows.1.Synthesis of optically active octahydroindole derivatives through asymmetric radical [3+2] cycloadditionIn last year, I reported asymmetric radical [3+2] cycloaddition using optically active bicyclic iodoaziridine. The product of the present reaction should be useful synthetic intermediate of various natural octahydroindole alkaloids. However, radical reaction is not generally useful for natural product synthesis, because remarkable decrease in the chemical yield is often observed by the scale up of the reaction. On the other hand, I found that the present reaction can scale up to 5 mmol without the decrease in the chemical yield and the stereoselectivity2.Radical cascade reaction of iodomethylcyclopropane derivative with dienes and enynesIn relation to the present reaction using iodoalkylated three-membered ring compound, I have reported iodine atom transfer radical [3+2] cycloaddition reaction using iodomethylcyclopropane having two electron-with drawing group on the ring. That is, in the present of triethylborane, the iodomethylcyclopropane efficiently generates allylated active methine radical which gives cyclopentane derivatives with good yields and stereoselectivities through the iodine atom transfer cycloaddition with various alkenes. In this year, I invesigated radical cascade reaction with dines and enynes. I found that the reaction of iodomethylcyclopropane with 1,4-dienes and 1,4-enynes gives bicycle [3.3.0] octane derivatives in good yields through [3+2] cycloaddition and subsequent 5-exo-cyclization.