【作者】 田均均；

【导师】 贺峥杰；

【作者基本信息】 南开大学 ， 有机化学， 2013， 博士

【摘要】 环化反应是从简单易得原料构建结构多样化的碳环、杂环的有效途径之一除了著名的Diels-Alder反应和金属催化的环化反应外,最近十几年来发展的亲核性叔膦催化的环化反应,也为构建复杂分子骨架提供了可靠的平台。由于叔膦催化通常具有反应条件温和及操作简便的特点,近年来叔膦催化的环化反应己成为化学家研究的热点,发展了许多不同类型的环化反应,为构建含有不同官能团和结构特点的环状骨架分子提供了新方法。叔膦催化的环化反应有其本身的底物范围。现有研究发现,Morita-Baylis-Hillman (MBH)醇的衍生物和缺电子联烯通常可方便地与叔膦作用,产生的活性偶极中间体易与不同类型的亲电试剂作用,从而实现多种环化反应。寻找具有适当反应活性的亲电试剂因而成为探索叔膦催化的环化反应的重要手段。缺电子共轭体系作为亲电试剂可参与多种环化反应,而膦催化下其参与的环化反应却鲜有报道。因此,本论文系统地探索了三类膦催化下缺电子共轭体系参与的新颖环化反应,并取得了以下结果。1.首次实现了三苯基膦催化下MBH碳酸酯作为一碳合成子与查尔酮衍生的不饱和亚胺之间的[1+4]环化反应。该反应具有较宽的底物适应范围和非对映体选择性,在温和条件下均能够以较高的收率生成相应的环化产物,同时,与叔膦催化下MBH衍生物或者联烯酸酯与缺电子亚胺的[3+2]环化反应不同,该[1+4]环化反应获得2-吡咯啉衍生物,为该类化合物的合成提供了有效的新方法。机理研究表明,该反应代表了首例磷叶立德与1,3-氮杂二烯的[1+4]环加成反应。2.根据磷叶立德与1,3-氮杂二烯的[1+4]环化反应模式,进一步探索了原位形成的磷叶立德活性中间体与缺电子共扼烯烃的环化反应,实现了叔膦催化下MBH衍生物与双氰基活化的共轭二烯之间的[1+4]环化反应,提供了高效合成多取代环戊烯的新方法。同时研究发现,底物分子的取代基对该反应的环化模式存在显著影响,通过调整底物取代基类型可以实现高度化学选择性的[1+4]环化反应和区域选择性的[3+2]环化反应。这些环化模式为合成重要的五元碳环化合物提供了有效途径。3.采用酯基活化的不饱和亚胺作为亲电试剂,首次实现了α-烷基取代的联烯酸酯与活化烯烃的膦催化[3+2]环化反应。该反应提供了构建含有一个全碳季手性中心的环戊烯骨架的新方法,与文献报道中其他膦催化的[3+2]环化反应构建全碳季手性中心的方法不同,该反应中季碳中心碳原子由联烯酸酯的α-位碳继承而来。机理研究表明,该反应经由活化烯辅助的质子迁移步骤完成环化反应,催化循环中关键一步氢迁移发生在联烯酸酯的β-位与γ-位碳原子之间,而非传统的Lu[3+2]环化反应中,氢迁移发生在联烯酸酯α-位与β-位碳原子之间。这一环化反应代表了一种新颖的叔膦催化联烯酸酯的[3+2]环化反应,并显著扩大了Lu[3+2]环化反应的底物范围。更多还原

【Abstract】 Annulation reaction is one of the most powerful tools for rapid assembly of structurally diverse carbo-and hetero-cycles from readily available substrates. Besides the existing annulation protocols such as Diels-Alder reaction and transition-metal catalyzed ring-closure reactions, during the last decade, nucleophilic phosphine catalytic annulation reactions have provided a reliable platform for efficient construction of complicated molecular architectures. Since tertiary phosphine catalysis generally features mild condition and simplicity of operation, recently a great deal of effort has been poured into this field of phosphine-catalyzed annulation reactions. As a result, an array of various phosphine-triggered annulations has been developed, providing new synthetic methodology for cyclic structures with diversity.Phosphine-catalyzed annulation reactions depend on a range of peculiar substrates. It is known that, upon treatment with tertiary phosphines, the Morita-Baylis-Hillman (MBH) derivatives and electron-deficient allenes readily generate reactive dipoles which are entrapped with varied electrophiles, leading to a number of annulation reactions. Consequently, exploring electrophiles with proper reactivity has become a key to develop phosphine-catalyzed annulations. Electron-deficient conjugated systems are often involved in a variety of annulation reactions as electrophiles. However, the phosphine-catalyzed annulations of electron-poor conjugated systems are rarely touched. Thus, in this dissertation three novel phosphine-catalyzed annulation reactions of electron-deficient conjugated systems have been systematically investigated, and the following results have been achieved.1. For the first time, a PPh3-catalyzed [1+4] annulation of MBH acetates as a C1synthon with α,β-unsaturated imines derived from chalcones has been developed. Under mild conditions, a broad scope of substrates readily afforded the [1+4] annulation products in good diastereoselectivity and high yield. In contrast with the phosphine-catalyzed [3+2] annulations of MBH derivatives or allenoates, this [1+4] annulation produced2-pyrolines instead, providing a facile access to this kind of heterocycles. Mechanistic investigation unveiled this [1+4] annulation reaction represents the first example of the [1+4] cycloaddition of phosphorus ylides and1,3-azadienes.2. Following the [1+4] annulation mode between phosphorus ylides and1,3-azadienes, the phosphine-catalyzed annulations of in situ formed phosphorus ylides and polar conjugated dienes have been further explored. As a result, a novel phosphine-catalyzed [1+4] annulation reaction between MBH derivatives and1,1-dicyano-1,3-dienes has been developed, providing a new method to synthesize polysubstituted cyclopentenes. It was also found that the substituents of substrates impose significant influence on the annulation mode. Through choosing differently substituted substrates, highly chemoselective [1+4] annulation or regioselective [3+2] annulation could be readily achieved, which provide facile access to five-membered carbocycles.3. For the first time, a phosphine-catalyzed [3+2] annulation reaction of a-substituted allenoates and ester-activated α,β-unsaturated imines has been developed, which provides new and efficient access to highly functionalized cyclopentenes with one all-carbon quaternary center. This reaction also represents a novel variation of the famous Lu [3+2] cycloaddition reaction. Our findings in this study unveiled that the ester-activated alkene-assisted formal [1,2]-proton shift between β-and γ-carbon of the allenoate could serve as an alternative pathway to facilitate formation of the Lu [3+2] cycloaddition product. This reaction is the first example of α-alkyl substituted allenoates engaged [3+2] annulation under phosphine catalysis, illustrating a scope expansion in the famous Lu [3+2] cycloaddition reaction.更多还原