氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

引用本文: 朱庆英, 沈海民, 杨祖金, 纪红兵. 氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应[J]. 催化学报, 2016, 37(8): 1227-1234. doi: 10.1016/S1872-2067(15)61122-6 shu

Citation: Qingying Zhu, Haimin Shen, Zhujin Yang, Hongbing Ji. Biomimetic asymmetric Michael addition reactions in water catalyzed by amino-containing β-cyclodextrin derivatives[J]. Chinese Journal of Catalysis, 2016, 37(8): 1227-1234. doi: 10.1016/S1872-2067(15)61122-6 shu

氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

a. 中山大学化学与化学工程学院化工系, 广东广州 510275;
b. 浙江工业大学化学工程学院, 浙江杭州 310014
基金项目:
国家自然科学基金（21425627，21376279）.

摘要: 在不对称Michael加成反应中，有机小分子如伯胺、吡咯烷类衍生物、（硫）脲类、手性方酰胺、联萘类、奎宁类、手性膦、离子液体和肽类等是目前使用的主要催化剂，如果能避免或少量使用有机溶剂，则更符合“绿色化学”的环境友好发展方向.β-环糊精的内腔疏水，而外部亲水，可以类似酶分子结合有机反应物，在水相体系进行催化反应.当β-环糊精分子上连接催化部位或结合部位时，能产生更优异的包结底物和诱导对映选择性的能力.目前基于β-环糊精衍生物构筑人工类酶催化剂用于不对称Michael加成反应的报道较少.本文通过亲核取代反应将氨基类有机小分子与单（6-O-p-甲苯磺酰基）-β-环糊精结合，得到9个氨基修饰β-环糊精衍生物CD-1-CD-9（收率在24.2%-64.9%，分子结构通过¹H NMR，¹³C NMR和ESI-MS表征确认），并用于室温水相体系不对称Michael加成的仿生催化反应，以期获得较好的催化反应活性和对映选择性.通过设计不同β-环糊精衍生物的修饰基团结构、改变反应介质pH值和反应底物结构，分析了Michael加成反应体系产物产率和对映选择性的变化，采用2D-¹H ROESY NMR、紫外吸收光谱、红外光谱和和量子化学计算，分析了β-环糊精衍生物和反应底物分子的包结状态，探究了反应过程机理.结果显示，在该水相体系中进行的不对称Michael加成反应产物产率和对映体过量值（ee值）受修饰基团结构、反应介质pH值和底物结构影响较大.当反应介质pH值低于6.0时，由于氨基分子被质子化而失去催化活性；当pH值为7.5时，获得中等水平的对映选择性，通过量子化学在ONIOM（B3LYP/6-31G（d）：PM3）水平上的优化计算发现，底物分子与β-环糊精衍生物的包结可以出现两种形式：当底物分子的活性部位接近β-环糊精衍生物小口端的修饰基团时，产生分子内催化，诱导反应产生较好的对映选择性；当底物分子的活性部位远离β-环糊精衍生物小口端的修饰基团时，产生分子间催化，几乎没有对映选择性，而这两种情况同时存在.当底物分子以较大的空间位阻与β-环糊精疏水性空腔结合时，产生较好的对映选择性，邻位取代的2-硝基-β-硝基苯乙烯比对位取代的4-硝基-β-硝基苯乙烯ee值更高，通过量子化学优化计算证实空间位阻效应.应用2-金刚烷酮与β-环糊精衍生物空腔形成竞争性的包结反应实验，产物产率和ee值都下降，说明β-环糊精衍生物的疏水性空腔是产生不对称诱导和催化活性不可或缺的部分，底物分子与β-环糊精衍生物的包结过程通过2D-¹H ROESY NMR和紫外吸收图谱获得确认.其中L-2-氨甲基吡咯烷修饰β-环糊精CD-1表现出较好的反应对映选择性，在溶剂（pH=7.5，0.5mol/LCH₃COONa-HCl）2mL，环己酮2mmol，2-硝基-β-硝基苯乙烯0.2mmol，CD-1用量0.04mmol，25℃反应96.0h的条件下，环己酮与2-硝基-β-硝基苯乙烯Michael加成产物的ee值达71%，产率为47%.该反应过程在β-环糊精衍生物的疏水性空腔内进行，修饰基团L-2-氨甲基吡咯烷与环己酮形成烯胺的催化反应.

关键词:

English

Biomimetic asymmetric Michael addition reactions in water catalyzed by amino-containing β-cyclodextrin derivatives

a. School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, Guangdong, China;
b. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
Received Date: 11 March 2016
Revised Date: 24 April 2016
Fund Project:
This work was supported by the National Natural Science Foundation of China (21425627, 21376279).

Abstract: Nine β-cyclodextrin derivatives containing an amino group were synthesized via nucleophilic substitution from mono(6-O-p-tolylsulfonyl)-β-cyclodextrin and used in asymmetric biomimetic Michael addition reactions in water at room temperature. The mechanism responsible for the moderate activity and enantioselectivity of the β-cyclodextrin derivatives was explored using nuclear magnetic resonance spectroscopy, namely 2D ¹H rotating-frame overhauser effect spectroscopy (ROESY), ultraviolet absorption spectroscopy, and quantum chemical calculations, which provide a useful technique for investigating the formation of inclusion complexes. The effects of the pH of the reaction medium, the β-cyclodextrin derivative dosage, the structure of the modifying amino group, and various substrates on the yield and enantioselectivity were investigated. The results indicated that these factors had an important effect on the enantiomeric excess (ee) in the reaction system. Experiments using a competitor for inclusion complex formation showed that a hydrophobic cavity is necessary for enantioselective Michael addition. A comparison of the reactions using 4-nitro-β-nitrostyrene and 2-nitro-β-nitrostyrene showed that steric hindrance improved the enantioselectivity. This was verified by the optimized geometries obtained from quantum chemical calculations. An ee of 71% was obtained in the asymmetric Michael addition of cyclohexanone and 2-nitro-β-nitrostyrene, using (S)-2-aminomethylpyrrolidine-modified β-CD as the catalyst, in an aqueous buffer solution, i.e., CH₃COONa-HCl (pH 7.5).

Key words:

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氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

English

Biomimetic asymmetric Michael addition reactions in water catalyzed by amino-containing β-cyclodextrin derivatives

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氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

English

Biomimetic asymmetric Michael addition reactions in water catalyzed by amino-containing β-cyclodextrin derivatives

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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