【作者】 王雷；

【导师】 唐瑞仁；

【作者基本信息】 中南大学 ， 有机化学， 2013， 硕士

【摘要】 L-脯氨酸及其衍生物为一类高效的有机手性小分子催化剂。与传统过渡金属手性催化剂和生物酶相比,有机小分子催化剂具有价格低、无毒、操作简单等优点。近年来,大量的L-脯氨酸衍生物类催被合成出来并广泛应用于催化不对称的Aldol反应,Michael加成反应和Mannich反应中,取得了较好结果。但也存在溶解性差,反应条件较难控制,有时需要加入添加剂等问题。针对有机小分子催化剂中的问题,论文设计并合成了系列含吡啶二甲酰基的脯氨酸衍生物类有机小分子催化剂：以市售的L-脯氨酸和吡啶-2,6-二甲酸(DPA)为起始物,经过羧基还原、氨基保护、羟基保护、叠氮化、叠氮还原、缩合等系列反应合成得到了三未见文献报导的L-脯氨酸衍生物：(S)-N2-(四氢吡咯-2-亚甲基)-N6-甲苯磺酰基吡啶-2,6-二羧基酰胺,(S)-N2-(2,4,6-三甲苯磺酰)-N6-(四氢吡咯-2-亚甲基)吡啶-2,6-二羧基酰胺和(S)-N2-((4-十二烷基苯基)磺酰基)-N6-(四氢吡咯-2-亚甲基)吡啶-2,6-二羧基酰胺；化合物的结构经红外光谱(FT-IR)和核磁共振氢谱(1H-NMR)得以确认,并对相关合成工艺进行了优化。旨在通过催化剂设计改进催化剂的催化活性和溶解性等性能。以环己酮和对硝基苯甲醛的Aldol反应作为模板反应系统地考察了上述化合物的催化性能,结果表明：以上三种化合物对不对称Aldol反应具有较好的催化性能,对映体过量值(ee值)最高达到了85%,非对映体过量值(dr值)最高达到了90：10；反应简单,室温下即可得到较高的产率和较高的立体选择性,无需额外加入添加剂,通过对底物的普适性研究显示催化剂对于酮具有较好的适应性但是对于醛的适用性不好；并对反应的机理进行了初步的探讨。更多还原

【Abstract】 Since2000, the early discovery of List and Barbas that L-proline was used as the catalyst for the enantioselective direct aldol reaction, asymmetric organic catalytic have been greatly developed and applied for highly enantioselective direct aldol reaction, Michael addition and Mannich reaction. Compared with the traditional chiral catalysts of enzyme and transition metal-chiral legend, the organocatalyst showed lots of advantages such as inexpensive, low toxicity and simply operation. However, the organocatalyst also owns some shortcomings as poor solubility, rigorous reaction condition and extra addition of additives et.al.To overcome the shortcomings, we designed and synthetized a series of L-proline derived organocatalysts containing pyridine-2,6-biformacyl.Commercial available L-proline and pyridine-2,6-dicarboxylic acid were taken as the starting materials, bifunctional L-prolinamide derivative organocatalysts were synthesized via the reduction of carboxyl, protection of amino and hydroxy, azidation et.al. These catalysts are (S)-N2-(pyrrolidin-2-ylmethyl)-N6-tosylpyridine-2,6-dicarboxamide,(S)-N2-(mesitylsulfonyl)-N6-(pyrrolidin-2-ylmethyl) pyridine-2,6-dicarboxamide and (S)-N2-((4-dodecylphenyl)sulfonyl)-N6-(pyrrolidin-2-ylmethyl)pyridine-2,6-dic ar-bo-xamide, all the organocatalysts and a part of important intermediates were confirmed by Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (’H-NMR). Some synthesis processes were refined in order to improve catalytic activity and solubility of the catalysts.Catalystic performance were performed by the reactions between cyclohexanone and p-nitrobenzaldehyde; the results suggested that these catalysts could catalyze Aldol reaction efficiently, with ee up to85%, dr up to90:10. High yield and stereoselectivity were obtained under simple conditions that room-temperature, without additive or water. Universality study showed that these catalysts could well apply to multifarious ketones, but gave disappointing results when aldehyde varies. Additionally, reaction mechanism was preliminary discussed.更多还原