新型手性胺的設計、合成及其手性識別

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(lián)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(jīng)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(xiàn)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210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(wǎng)狀超分子結構。核磁共振波譜研究表明：該新型

2、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-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(xiàn)：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(xiàn)：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(xiàn)出優(yōu)異的催化活性和立體選擇性，在室溫下反應1248小時，得到收率高達97的Michael產(chǎn)物，

3、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(xiàn)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(lián)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Michaelaldol串聯(lián)反應Novel Chiral Amines: Design, Preparation

4、 and Properties in Chiral Recognition and Asymmetric Organocatalysis ABSTRACTIn this dissertation, the recent advances in the asymmetric organocatalysis and especially in chiral amine catalyzed enantioselevtive Michael addition reactions were summarized and reviewed. Then, novel classes of chiral am

5、ines 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 designed and synthesized efficiently from natural amino acids. They could behave like ionic liquid

6、s with low melting point (Tm) or glass transition temperature (Tg) and good thermal stability (Tdec210). X-ray diffraction analysis result confirmed their netlike supramolecular structures formed through the hydrogen bonding and the electrostatic attraction. The NMR chiral recognition study indicate

7、d that these novel ICAs could provide efficient chiral environment and good enantiometic discrimination to Mosher acid was achieved by 19F NMR.Secondly, the novel chiral-amine-thioimidazoles were designed and synthesized by treating (S)-bromine-substituted alkylamine hydrongen bromide salt with 1-al

8、kyl-2-mercaptoimidazole, and their structures were characterized by NMR、IR、MS and X-ray diffraction analysis. 19F NMR and 1H NMR measurements also indicated that they had excellent enantiomeric acid recognition properties due to their multifunctionalties. Thirdly, novel pyrrolidinyl-thioimidazolium

9、salts were developed as chiral multifunctional organocatalysts. ESI-MS spectrometric detection gave the apparent evidence for the ionic organocatalyst coordination ability of polyethylene glycols (PEGs) to form the like supramolecular structure. The unique stable PEGs-ionic-pyrrolidine complex was a

10、pplied 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 complex system and the resulting freely dissociable anion were considered to distribute to the excellent

11、performance of the organocatalysts.Lastly, the novel (S)-pyrroline-thioimidazolium salts were further applied and exhibited good catalytic performance in the asymmetric Michael-aldol tandem reactions of ,-unsaturated aldehydes and 2-hydroxybenzaldehyde to form the chiral benzopyran derivatives as well. The desired products were