【作者】 陈维；

【导师】 陈应春； 吴勇；

【作者基本信息】 四川大学 ， 药物化学， 2007， 博士

【摘要】 本课题研究了两方面的内容。第一部分：基于亚胺离子活化的不对称有机催化反应研究；第二部分：硫脲-钯配合物催化的Heck和Suzuki反应研究。不对称有机小分子催化已经成为不对称合成领域至关重要的组成部分。小分子催化所实现的全新的底物活化方式给人们提供了除过渡金属催化剂外的更多的选择。值得关注的是，小分子催化最年轻分支之一的亚胺离子活化领域已经随着小分子催化的发展而日臻成熟。本文研究发现，简单易得的α，α-二芳基脯胺醇的盐能非常有效的催化偶氮次甲基亚胺和α，β-不饱和醛的不对称[3+2]偶极环加成反应。同时，催化剂芳基的取代基的电子效应对反应影响很大，具有强拉电子基的催化剂表现出高的立体选择性和催化剂活性。在室温下反应，便可方便的制得一系列高对映选择性连续多手性中心的双吡唑烷-3-酮衍生物(81:19 to 98:2 exo:endo，77-97% ee forexo product)。在继续研究基于亚胺离子活化的不对称有机反应研究时，我们把目光投向未解决好的吲哚和简单α，β-不饱和酮的不对称Friedel-Crafts反应。我们首次发现从天然金鸡纳碱衍生的手性伯胺催化剂能有效的催化吲哚和简单α，β-不饱和酮的不对称付克反应，得到中等到良好的对映选择性(47-89% ee)。我们从天然金鸡纳碱出发，设计了新的多功能手性伯胺催化剂。首次发现该催化剂能高效的催化偶氮次甲基亚胺和环状α，β-不饱和酮的不对称[3+2]偶极环加成反应(endo:exo:>99:1，86-95%ee)。催化剂中引入的羟基对催化剂和1,3-偶极之间的氢键形成至关重要，而这又直接影响反应的对映选择性。这也是首次观察到亚胺离子催化过程中催化剂对不同底物活化的协同作用。我们设计并合成了大位阻的非环状和环状双硫脲配体，发现双硫脲能和钯形成非常稳定的配合物。对于碘苯和溴苯的Heck和Suzuki反应，能得到高的TON值和TOF值(对于碘苯，TON值高达1000000，TOF值高达200000；对于溴苯TON值高达89000)。通过核磁和ESI-MS研究，我们证实催化剂的活性形式是双硫脲和钯1:1配合。我们进一步设计并合成了大位阻，结构刚性的双硫脲配体，并成功的将得到的自组装硫脲钯配合物应用于对于芳基溴和苯硼酸的水相Suzuki反应中。催化剂可以方便的回收。更多还原

【Abstract】 Two projects were investigated in my dissertation. The first part was about organocatalytic asymmetric reactions based on iminium activation, the second part was on Heck and Suzuki reactions catalyzed by thiourea-palladium complex.Enantioselective organocatalysis has become a field of central importance for the asymmetric synthesis of chiral molecules. Novel modes of substrate activation have been achieved using organic catalysts that can now deliver unique, orthogonal, or complementary selectivities comparable to many established metal-catalyzed transformations. Notably, the concept of iminium catalysis, one of the youngest subfields of organocatalysis, has grown almost hand in hand with the general field of organocatalysis.In the current work, readily availableα,α-diarylprolinol salts were found to be active catalysts for the stereoselective [3+2] dipolar cycloadditions of azomethine imines withα,β-unsaturated aldehydes. The catalyst with strongly electron-withdrawing groups exhibited high stereoselectivity and catalytic activity in the cycloaddtion reactions. Variously structured enantiomerical bipyrazolidin-3-one derivatives with multiple contiguous chiral centers were smoothly prepared under mild conditions (81:19 to 98:2 exo:endo, 77-97% ee for exo product).During our continuous studies on the organocatalysis based on iminium strategy, we are interested in the undeveloped asymmetric reactions between indoles andα,β-unsaturated ketones. We found that a chiral primary amine derived from natural cinchonine was an efficient organocatalyst for the asymmetric Michael-type Friedel-Crafts alkylations of indoles andα,β-unsaturated alkyl ketones for the first time. Moderate to high enantioselectivity (47-89% ee) has been achieved.Novel organocatalysts have been designed based on multifunctional primary aminocatalysts derived from cinchona alkaloids to catalyze the first organocatalytic and highly enantioselective 1,3-dipolar cycloaddition of cyclic enones and azomethine imines (endo:exo : > 99:1, 86-95% ee). The additional hydrogen bonding interaction of catalyst and 1,3-dipole is essential for the stereocontrol. To the best of knowledge, this is the first example which involves the synergistic activation of reactants in iminium catalysis.We firstly presented the synthesis of the bulky N,N-disubstituted acyclic and cyclic bis-thiourea ligands. They acted as strong coordinating ligands for palladium and the complexes demonstrated high thermal stability. Good catalytic activity for aryl iodides and bromides in Heck and Suzuki coupling reactions was exhibited under aerobic conditions for the bis-thiourea-Pd catalysts, and high TONs and TOFs were achieved (for PhI, TONs up to 1 000 000, TOFs up to 200 000; For activated bromide, TONs up to 89 000)). Moreover, spectroscopic investigation of the bis-thiourea-Pd complexes demonstrated that the active catalyst was the chelating specie in a.1:1 ratio.We have designed and synthesized the bulky and rigid bis-thiourea ligands, and the self-supported thiourea-PdCl2 complexes were firstly prepared. They acted as efficient heterogeneous catalysts in the Suzuki reaction of aryl bromides and aryl boronic acids in neat water under aerobic conditions. Moreover, facile recovery use of the heterogeneous catalysts was demonstrated without palladium leaching.更多还原