基于新型硫脲—双膦配体过渡金属—有机小分子共催化的不对称氢化研究

发布时间：2018-04-13 16:32

本文选题：硫脲-双膦配体 + 双功能活化　；参考：《浙江工业大学》2017年博士论文

【摘要】：过渡金属与有机小分子共催化的策略(例如cooperative catalysis,sequential/relay catalysis以及synergistic catalysis),因其独特的催化模式受到广泛的关注。经过近十年发展和较系统研究,这一策略已经攻克了很多挑战性的不对称催化体系。最近,我们课题组基于硫脲-双膦配体双功能活化策略,巧妙地将两种类型的配体键合到一个分子结构中,在有机小分子活化底物的基础上实现过渡金属催化的新策略,并在多个挑战性的不对称氢化反应中得到展示。本论文进一步将该体系拓展到更多类型的不饱和官能团化烯烃的不对称氢化中,研究发现在硝基烯酰胺和α,β-不饱和-N-酰基吡唑等两个体系中有很好的反应活性以及对映选择性。反应产物可以进一步衍生化,用作有机合成和药物合成的重要中间体。论文主要研究内容如下。1.成功地发展了Rh/Zhaophos催化体系对于硝基烯酰胺类底物的不对称氢化反应。在优化条件下,该反应能够取得很好的转化率以及ee值(转化率99%,ee值最高达96%)。反应产物,手性β-氨基硝基化合物,可以转化为一系列药物中间体或者其他具有生物活性的分子,例如Voseltamivir,GR-205171A,(+)-CP-99.994,Asimadoline。2.成功地将Rh/Zhaophos催化体系运用到α,β-不饱和-N-酰基吡唑的不对称氢化反应中。研究结果表明该催化体系具有很好的反应活性(转化率99%)以及很高的对映选择性(ee值最高达99%)。控制实验结果表明,底物和配体间的氢键作用力在不对称氢化中起到了重要作用。反应产物(手性吡唑酰胺类化合物)脱除吡唑基团后衍生得到相应的手性羧酸化合物,也是重要的手性合成或药物合成的中间体。3.成功地发展了Rh/Zhaophos催化体系对于氮杂卓/氧氮杂卓类型的七元环亚胺盐酸盐的不对称氢化反应。在优化条件下,该反应能够取得很好的转化率以及ee值(转化率99%,ee值最高达99%)。控制实验结果表明,底物的氯离子和zhaophos的硫脲基团之间的离子对相互作用力对于该体系取得的高对映选择性具有至关重要作用。
[Abstract]:The strategies of co-catalysis of transition metals with small organic molecules (such as cooperative catalyst sequentialrrelay catalysis and synergistic catalyst) have attracted much attention for their unique catalytic modes.After nearly a decade of development and systematic research, this strategy has overcome many challenging asymmetric catalytic systems.Recently, based on the bifunctional activation strategy of thiourea-bisphosphine ligands, our team cleverly bonded two types of ligands into a single molecular structure to realize a new strategy of transition metal catalysis based on the activation of organic small molecules.It has been demonstrated in several challenging asymmetric hydrogenation reactions.In this paper, the system was further extended to the asymmetric hydrogenation of more unsaturated alkenes. It was found that the system had good reactivity and enantioselectivity in the two systems of nitrilenamide and 伪, 尾 -unsaturated -N-acylpyrazole.The reaction products can be further derivatized and used as important intermediates in organic synthesis and drug synthesis.The main contents of this paper are as follows. 1.The asymmetric hydrogenation of nitrilenamide substrates with Rh/Zhaophos catalyst system was successfully developed.Under the optimized conditions, good conversion and ee value can be obtained.The reaction product, a chiral 尾 -amino-nitro compound, can be converted into a series of pharmaceutical intermediates or other bioactive molecules, such as Voseltamivirus GR-205171An (CP-99.994Asimadoline.2).The Rh/Zhaophos catalyst system was successfully applied to the asymmetric hydrogenation of 伪, 尾 -unsaturated -N-acylpyrazole.The results show that the catalytic system has good reaction activity (conversion 99) and high enantioselectivity ee value up to 99%.The experimental results show that the hydrogen bond force between substrate and ligand plays an important role in asymmetric hydrogenation.The reaction product (chiral pyrazolamide) was derived from the pyrazole group to obtain the corresponding chiral carboxylic acid compound, which is also an important intermediate of chiral synthesis or drug synthesis.The asymmetric hydrogenation of azazepines / oxazazepines was successfully developed in the Rh/Zhaophos catalytic system.Under the optimized conditions, good conversion and ee value can be obtained.The results show that the ion pair interaction between the chloride ions of the substrate and the thiourea group of zhaophos plays an important role in the high enantioselectivity of the system.
【学位授予单位】：浙江工业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

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