Development of Efficient Methods for the Synthesis of Medium- and Large-Sized Carbocycles with the Aid of Samarium

利用sml_2促进的分子内Reformatsky反应，在温和条件下制备了环骨架全部由sp^3碳组成的中、大尺寸碳环化合物。该反应似乎是通过硝酸钐中间体进行的，这是连续的2 -ekx-tron还原a-溴酯的结果。钐的离子半径大、配位灵活、亲氧性高等特性对环化反应起着重要作用：与钐相连的大尺寸螯合物，其碳-碳键形成过程类似环状收缩，而环化后的六元螯合物可能参与了这一过程。在质子源存在下，采用Sml_2-THF-HMPA还原体系，在室温下实现了共轭酯的瞬间加氢二聚，并在N， N-二苄基克罗顿酰胺反应中实现了完美的立体选择。然而，该方法不能成功地应用于大环化。结合本研究，还开发了一种利用sml_2促进的电子转移过程选择性还原α、β -不饱和酯和amkles的高效方法。在初步实验中，Pinacol与镧系三酸盐-碘化钐体系偶联反应可获得中等产率的中等碳循环。这种方法似乎很有前途，正在本实验室进一步研究。所有其他开发有用的环化方法以获得中等碳环的努力都以失败告终：尝试的方法是(i) w-氧烯丙基卤化物的分子内barbier型反应，（ii）丙环缩合反应，以及（iii）酮-烯或酮-炔还原偶联反应。但是，最后一种方法被发现是有效的碳-碳自由基成键反应。

Medium- as well as large-sized carbocyclic compounds whose ring skekitorls are composed entirely of sp^3 carbons have been prepared in high yields under mild conditions by utilizing Sml_2-promoted intramolecular Reformatsky reaction. The reaction seems to proceed through samarium enorate intermediate as the result of successive two-ekx-tron reduction of a-bromo esters. The distinct property of samarium such as large ionic radius, flexible coordination, and high oxophilicity should play an important role for the cyclizadion : The samarium-linked large-sized chelate, from which the carbon-carbon bond formation would take place like a ring contraction, and the six-membered chelate after cyclization might be involved in the process.Conjugated esters were instantaneously hydrodimerized at room temperature by use of the reduction system, Sml_2-THF-HMPA, in the presence of proton sources, and perfect stereoselection was realized in the reaction of N, N-dibenzyl crotonamide. However, the method could riot be successfully applied to macrocyclization. In connection with the present study, a very efficient method for the selective reduction of alpha, beta-unsaturated esters and amkles via Sml_2-promoted electron transfer process was also developed.Pinacol coupling reaction with lanthanide triflate-samarium (II) iodide system afforded medium-sized carbocycle in moderate yield in the preliminary experiment. This approach seems to be promising and is being further studied in this laboratory.All other efforts to develop useful cyclization methods to botain medium-sized carbocycles ended in failure : The attempted methods are (i) intramolecular Barbier-type reaction of w-oxo allylic halides, (ii) acyloin condensation, and (iii) ketone-alkene or ketone-alkyne reductive coupling reaction. But, the last method was found to be useful as carboncarbon bond-forming reaction via radical process.