Synthesis of Biologically Active Compounds Based on the Regio- and Stereo-Controlled Radical Cyclizations

1.烯键末端含硫原子或腈基的ω-卤代烯烃的自由基环化反应均以外向方式进行。对实验结果进行了机理分析，并将其应用于（±）-伊巴比丁和（±）-毒扁豆碱关键中间体的合成.采用5-外环自由基环合立体选择性合成了（3R^*，3aS ^*，7aS^*）-3-芳八氢吲哚-2-酮，并将该方法应用于（±）-泛克拉辛的形式合成.发现N-乙烯基2-碘苯甲酰胺自由基反应生成6-内环化产物是通过连续的5-外芳基环化和新叶基重排进行的.在N-（邻溴苄基）烯酰胺自由基环化反应的研究中，首次发现了烯键上无取代基的烯烃生成6-内环化产物的例子。我们还发现，在末端有两个苯硫基或N-乙烯基键的烯酰胺进行自由基环化在5-exo方式排他性。后一种方法应用于抗疱疹病毒化合物马匹辛酮模型化合物的合成.在卤代化合物的自由基反应中，碘原子的使用被认为比氯原子的使用产生更好的结果。我们惊奇地发现，在α-卤代酰胺的5-内环化反应中，使用氯原子可以得到高产率的环化产物，而使用碘原子只能得到有限量的预期环化产物。发展了Mu（OAc）_3/Cu（OAc）_2介导的α-甲硫基酰胺的氧化自由基环化反应，并将该方法应用于一种简洁的藜芦烷骨架的构建。

1. Radical cyclization of ω-haloalkenes having a sulfur atom or a nitrile group at the terminus of their alkenic bond was found to undergo in an exo manner exclusively. A mechanistic rationalization for the results was proposed and the methods were applied to the syntheses of the key intermediates for (±)-ipalbidine and (±)-physostigmine.2. Stereoselective synthesis of (3R^*, 3aS^*, 7aS^*)-3-aryloctahydroindol-2-ones using 5-exo radical cyclization was developed and the method was applied to a formal synthesis of (±)-pancracine.3. Formation of 6-endo cyclization products by radical reaction of N-vinylic 2-iodobenzamides was found to proceed through a consecutive 5-exo aryl radical cyclization and neophyl rearrangement.4. In the course of the study on the radical cyclization of N-(ο-bromobenzyl) enamides, we found a first example of the formation of 6-endo cyclization product onto alkene having no substituent on the alkenic bond. We also found that the enamides having two phenylthio groups at the terminus or the N-vinylic bond underwent radical cyclization in a 5-exo manner exclusively. The latter method was applied to the synthesis of a model compound of mappicine ketone, an anti-herpesvirus compound.5. The use of an iodine atom is recognized to give a better result than does that of a chlorine atom in the radical reactions of halogeno compounds. We found, surprisingly, that in the 5-endo cyclization of α-halo amides, the use of a chlorine atom gave the cyclization products in high yields, whereas that of an iodine atom gave only a limited amount of the expected cyclization product.6. Mu(OAc)_3/Cu(OAc)_2-mediated oxidative radical cyclization of α-(methylthio) amides was developed and the method was applied to a concise construction of an erythrinane skeleton.