【作者】 陈祖良；

【导师】 路勇； 张俊良；

【作者基本信息】 华东师范大学 ， 物理化学， 2012， 博士

【摘要】 环状(杂环或者碳环)化合物广泛存在于大多数具有重要生物活性的天然产物和药物分子中。因此,发展一些新型有效的环化/环加成反应对于天然产物全合成和发现有潜在生物活性的分子有着十分重要的意义。本论文的研究工作有两大部分组成：(1)环氧乙烷衍生物的环化反应及机理研究；(2)缺电子烯炔化合物的环化反应研究。在论文的第一部分我们首次实现了活化的环氧化合物在路易斯酸催化下的碳-碳键选择性断裂并形成羰基叶立德中间体,该中间体能被醛所捕获。首先,我们设计合成了一系列环氧乙烷基二酮类化合物。经过条件优化,我们发现该化合物和醛在Yb(OTf)3的催化下,能以高非对映选择性和高化学选择性得到多取代的1,3-二氧杂环戊烷类化合物。当我们把环氧乙烷的活化基团换成二酯时,实现了该类化合物和醛的化学选择性环化。经过大量的条件摸索,最终在Sn(OTf)2做催化剂时,得到了基于C-O键断裂的环化产物；在Ni(ClO4)2做催化剂时,得到了基于C-C键断裂的环化产物,提出了导致这种不同断键的可能反应机制,并对该机制给予计算化学和实验上的验证。最后我们还实现了Ni(ClO4)2催化下1-芳基环氧乙烷和环氧乙烷基二酯的环加成反应,值得说明的是,在该反应中Ni(ClO4)2起到了双活化的功能。在论文的第二部分我们以三乙胺为碱,实现了缺电子烯炔和巴豆酸酯衍生的锍盐的环化反应,可以快速高效地得到一系列多官能团化的4-亚烷基二环[3.1.0]己烯类衍生物。我们还发展了缺电子烯酮和修饰的MBH产物在三苯基膦催化下的[4+1]环加成反应,以高区域选择性和高非对映选择性构建了一系列多取代的二氢呋喃产物。在该反应中修饰的MBH产物是作为一碳组分参与到反应中的,不同于Lu等人报道的修饰的MBH产物作为三碳组分参与的[3+n]环加成反应。更多还原

【Abstract】 Cyclic compounds are present in many natural products and medicinal molecules with biological activity. Therefor, it is very important to develop some novel and efficient cyclization reactions for synthesis of natural products and construction of a wide range of molecules with potential biological activity. This thesis mainly consist of two parts:(1) cyclization of oxirane derivatives and their mechanism study,(2) cyclization of electron-deficient enynes.In the first part, we established for the first time an efficient approach to carbonyl ylides which trapped with aldehydes by Lewis acid catalyzed chemoselective C-C bond hetorolysis of activated oxiranes. Initially, We synthesized various rationally designed aryl oxiranyl diketones. After numerous attempts, we found that the reaction of aryl oxiranyl diketones and aldehydes proceeded smoothly to afford highly substituted1,3-dioxolanes with excellent diasteroselectivity and chemoselectivity under the catalysis of Yb(OTf)3. When the activated groups were switched to dicarboxylates, we achieved chemodivergent cycloaddtion reactions of activated oxiranes with aldehydes. The reaction worked well to produce the corresponding cycloadduts with C-O bond cleavage of oxiranes under the catalysis of Sn(OTf)2, however, the expected1,3-dioxolanes with C-C bond cleavage of oxiranes were obtained when the Ni(ClO4)2was involved. Based on a series of control experiments and computational study, a mechanism was proposed. Finally, the cycloaddition reactions of styrenyl epoxides and aryl oxiranyl dicarboxylates catalyzed by Ni(ClO4)2was also achieved in mild conditions. It is noteworthy that dual activation of both the two reagents is the key to this reaction.In the last part, we developed a novel tandem Michael addition and ylide annulation of a crotonate-derived sulfur ylide with readily available electron-deficient enynes catalyzed by Et3N, which provide a rapid, efficient and selective route to multi-functionalized4-alkylidenebicyclo-[3.1.0]hex-2-enes. We also discovered an unexpected phosphine-catalyzed regio-and diastereoselective [4+1] annulation reaction of modified Morita-Baylis-Hillman adducts with activated enones to afford multifunctionalized dihydrofurans. In these annulations, Morita-Baylis-Hillman carbonates act as the one carbon unit, which is distinguished from Lu et al. reported modified allylic compounds as the three carbon units in [3+n] annulation reactions.更多还原