新型手性胺的設計、合成及其手性識別(精)

1、新型手性胺的設計、合成及其手性識別與不對稱催化性能研究摘要本論文首先較全面地歸納和綜述了有機不對稱催化， 特別是手性 胺催化不對稱 Michael 加成反應研究進展，在此基礎上，對新型手性 胺的設計、制備、表征及其手性設別和不對稱催化 Michael 加成和 Michae-aldol 串聯反應性能進行了較深入的研究。設計合成了一類以氨基酸為原料，經還原、溴化、季銨化和離子 交換反應得到的新型離子化手性胺。 該類離子化手性胺表現出離子液 體的特性，具有較低的玻璃化溫度和良好的熱穩(wěn)定性（Tdec在210C以上）。其晶體結構表明質子化的手性胺通過形成氫鍵和離子鍵等形 式構建成穩(wěn)定的網狀超分子結構。

2、核磁共振波譜研究表明： 該新型離 子化手性胺可提供有效的手性環(huán)境，具有明顯的手性識別性能。設計了一類新型手性胺硫基咪唑類化合物， 并通過氨基酸衍生 物a溴代脂肪胺氫溴酸鹽與巰基咪唑進行硫醚化反應高收率高選擇 性地得到該類化合物，其結構通過 NMR、IR、MS和X-射線單晶衍 射分析確認。 在核磁共振波譜研究中發(fā)現： 該類化合物對外消旋酸具 有良好的手性識別性能。ESI-MS分析發(fā)現：以設計的（S）-吡咯烷硫基咪唑與質子酸形成 的離子型手性胺可有效地被 PEG800 包裹，形成類似超分子結構的穩(wěn)定催化體系，在酮與硝基烯烴的不對稱 Michael 加成反應中表現出 優(yōu)異的催化活性和立體選擇性，在室

3、溫下反應1248小時，得到收率高達97%的Michael產物，d/r比大于90: 10, ee值高達99%。該 離子型手性胺 PEGs 催化體系還具有良好的穩(wěn)定性，可穩(wěn)定重復使 用 7 次以上。聚乙二醇包裹陽離子和陰離子的有效游離是顯現優(yōu)異催 化性能的主要原因。設計的（S）-吡咯烷-硫基咪唑鹽在烯醛與水楊醛的不對稱 Michaelaldol 串聯反應合成手性苯并吡喃衍生物中也具有良好的催 化性能。由于催化劑中的硫醚基團與底物水楊醛之間的靜電相互作 用，不對稱誘導生成以S構型為主的苯并吡喃衍生物。關鍵詞：離子化手性胺，手性胺硫基咪唑， 手性識別，不對稱 Michael 加成，不對稱 Michae

4、laldol 串聯反應Novel Chiral Amines: Design, Preparation and Properties inChiral Recognition and Asymmetric OrganocatalysisABSTRACTIn this dissertation, the recent advances in the asymmetric organocatalysisand especially in chiral amine catalyzed enantioselevtive Michael addition reactions were summarize

5、d and reviewed. Then, novel classes of chiral amines were extensively studied on their design, preparation, characterization and properties in chiral recognition and asymmetric organocatalysis.Firstly, a novel class of ionic chiral amines (ICAs) was designedand synthesizedefficiently from natural am

6、ino acids. They could behavelike ionic liquids with low melting point (Tm) or glass transition temperatureT(g) and good thermal stability (Tdec210C). X-ray diffraction analysis result confirmed their netlike supramolecular structures formed through the hydrogen bonding and the electrostatic attracti

7、on. The NMR chiral recognition study indicated that these novel ICAs could provide efficient chiral environment and good enantiometic discrimination to Mosher acid was achieved by19F NMR.Secondly, the novel chiral-amine-thioimidazoles were designed and synthesized by treating (S)-bromine-substituted

8、 alkylamine hydrongen bromide salt with 1-alkyl-2-mercaptoimidazole,and their structures were19 characterized by NMR、 IR、MS and X-ray diffraction analysis. 19F NMR1and H NMR measurementsalso indicated that they had excellent enantiomeric acid recognition properties due to their multifunctionalties.T

9、hirdly, novel pyrrolidinyl-thioimidazolium salts were developed as chiral multifunctional organocatalysts. ESI-MS spectrometric detection gave the apparentevidence for the ionic organocatalystcoordination ability of polyethylene glycols (PEGs) to form the like supramolecular structure. The unique st

10、able PEGs-ionic-pyrrolidine complex was applied as a highly efficient and reusable system for the direct enantioselective Michael addition of ketones to nitroalkenes with 7097% yields and up to 99% ee enantioselectivities obtained. The complexsystem and the resulting freely dissociable anion were co

11、nsidered to distribute to the excellent performance of the organocatalysts.Lastly, the novel S( )-pyrroline-thioimidazolium salts were further applied and exhibited good catalytic performance in the asymmetric Michael-aldol tan dem reacti ons of a B -un saturated aldehydes and 2-hydroxybenzaldehyde to form the chiral benzopyran derivatives as well. The desired products