【作者】 高军龙；

【导师】 李耀先； 张锁秦；

【作者基本信息】 吉林大学 ， 有机化学， 2009， 博士

【摘要】 有机催化剂催化的不对称合成反应是近年迅速发展起来的一个研究领域,设计、合成具有高活性、高选择性、可以循环利用的有机催化剂是该领域的前沿。本文以天然的手性氨基酸为原料,经保护、酰胺化、脱保护等6步反应合成出9个末端带吡啶环的二肽衍生物,又以4-羟基-L-脯氨酸为原料合成二肽催化剂,然后以4位羟基为活性位点通过和三乙氧基硅基丙基异氰酸酯反应将催化剂固载到硅胶上,固载量为0.43mmol/g,从而对固载催化剂的方法进行初步探讨研究,采用本文合成的催化剂催化环己酮与芳香醛的不对称直接aldol反应,详细地考察了反应温度、溶剂、催化剂用量、添加剂等因素对反应活性和对映选择性的影响。研究结果表明催化剂表现出较好的催化活性和对映选择性,在优化的反应条件下,aldol产物的产率最高达96%,ee值最高可达94%,dr值最高>99:1。此类催化剂在环己酮与硝基苯乙烯的nitro-Michael,也表现出一定的的催化活性,产率最高达91%,dr值最高达99:1,ee最高达70%。通过偶联反应将催化剂1固载到硅胶上,并将其用于催化环己酮和硝基苯甲醛的aldol反应,dr值最高达到90:10,ee最高76%。催化剂重复6次以上,催化活性几乎没有变化,为今后硅胶固载催化剂和催化剂的回收利用提供了经验借鉴。本文在大量合成实验的基础上,归纳总结二肽衍生物的合成条件和方法,为新颖有机小分子催化剂的进一步合成奠定了基础,同时也为催化剂的固载提供了经验。更多还原

【Abstract】 Organocatalysts have widely applications in the field of asymmetric synthesis, especially, enantioselective C-C bond forming reactions,such as aldol reaction, Michael reaction, etc. Recently, many researchers have focused on the design and synthesis of new and highly efficient organocatalystsIn this paper, we incorporated both prolinamide moieties and aminopyridine in one molecule could give the potential organocatalysts.Boc-1～Boc-9 (65%～92%,yield )were synthetized by mixed anhydride method or DCC condensation using N-Boc-L- proline N-Boc-4-OH-L-proline and Picolinamide respectively, Finally, the catalysts 1-9 were synthesized after being deprotected by TFA.The aldol reaction is one of the most important organic reactions, because it is a carbon-carbon bond forming reaction which produces highly functionalized compounds with a pair of newly generated chiral centers. We first examined the ability of the catalysts 1-9 to promote the direct aldol reaction between cyclohexanone and 4-nitrobenzaldehyde under various conditions. Catalysts 1, 4 and 9 are identified as the best catalysts for this reaction which lead to aldol adduct with excellent enantioselectivity and ee value up to 96%, dr value upto >99:1.The reactions of different aromatic aldehydes with cyclohexanone were studied under the optimized conditions (using 20 mol% of 1 as catalyst in CHCl3). The reactions of different aromatic aldehydes, which bear an electron-withdrawing group on the benzene ring, proceeded smoothly in excellent enantioselectivities (ee 94%, dr> 99:1) to furnish the aldol adducts. In addition, halogenated benzaldehydes led to decreased yields. Interestingly, the ee values of the products remained at good levels. On the other hand, this catalytic system was proven to be completely ineffective for the aromatic aldehydes with an electron-donating group or without any substitution.The Michael reaction is also an important C-C bond forming reaction in organic synthesis. We investigated the application of catalysts 1, 4and 9 for the Michael reaction between cyclohexanone and trans-β-nitrostyrene under the optimized reaction conditions. In the presence of 10 mol% catalyst loading, catalysts 1, 4 and 9 gave the product of cyclohexanone reacting with trans-β-nitrostyrene in moderate yield (up to 91% yield) and high diastereoselectivity( dr up to 99:1), but poor poor to moderate enantioselectivity( up to 70%, ee).The catalyst 1 was supported using Mesoporous-silica. We first examined the ability of the catalyst to promote the direct aldol reaction between acetone and 4-nitrobenzaldehyde under various conditions. Resultly, The catalyst had moderater catalytic activity ( ee 76, dr 90:10). The supported catalyst could be easily separated from the reaction system by filtration and reused at least six times without significant lost of activity and enantioselectivity.Via the researching work of this dissertation, suggest a new strategy in the design of new organocatalystss for direct asymmetric aldol reactions and related reactions and make the design and synthesis of catalyst possible to multiple reactions. While, our work provide experience for silica supported organocatalyst.更多还原