新型手性胺的设计、合成及其手性识别(精)

新型手性胺的设计、合成及其手性识别

与不对称催化性能研究

摘要

本论文首先较全面地归纳和综述了有机不对称催化，特别是手性胺催化不对称Michael加成反应研究进展，在此基础上，对新型手性胺的设计、制备、表征及其手性设别和不对称催化Michael加成和Michae-aldol串联反应性能进行了较深入的研究。

设计合成了一类以氨基酸为原料，经还原、溴化、季铵化和离子交换反应得到的新型离子化手性胺。该类离子化手性胺表现出离子液体的特性，具有较低的玻璃化温度和良好的热稳定性（T dec在210℃以上）。其晶体结构表明质子化的手性胺通过形成氢键和离子键等形式构建成稳定的网状超分子结构。核磁共振波谱研究表明：该新型离子化手性胺可提供有效的手性环境，具有明显的手性识别性能。

设计了一类新型手性胺－硫基咪唑类化合物，并通过氨基酸衍生物α-溴代脂肪胺氢溴酸盐与巯基咪唑进行硫醚化反应高收率高选择性地得到该类化合物，其结构通过NMR、IR、MS和X-射线单晶衍射分析确认。在核磁共振波谱研究中发现：该类化合物对外消旋酸具有良好的手性识别性能。

ESI-MS分析发现：以设计的(S)-吡咯烷－硫基咪唑与质子酸形成的离子型手性胺可有效地被PEG－800包裹，形成类似超分子结构的

稳定催化体系，在酮与硝基烯烃的不对称Michael加成反应中表现出优异的催化活性和立体选择性，在室温下反应12～48小时，得到收率高达97％的Michael产物，d/r比大于90：10，ee值高达99％。该离子型手性胺－PEGs催化体系还具有良好的稳定性，可稳定重复使用7次以上。聚乙二醇包裹阳离子和阴离子的有效游离是显现优异催化性能的主要原因。

设计的(S)-吡咯烷－硫基咪唑盐在烯醛与水杨醛的不对称Michael－aldol串联反应合成手性苯并吡喃衍生物中也具有良好的催化性能。由于催化剂中的硫醚基团与底物水杨醛之间的静电相互作用，不对称诱导生成以S构型为主的苯并吡喃衍生物。

关键词：离子化手性胺，手性胺－硫基咪唑，手性识别，不对称Michael 加成，不对称Michael－aldol串联反应

Novel Chiral Amines: Design, Preparation and Properties in Chiral Recognition and Asymmetric Organocatalysis

ABSTRACT

In 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 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 designed and synthesized efficiently from natural amino acids. They could behave like ionic liquids with low melting point (T m) or glass transition temperature (T g) and good thermal stability (T dec≥210℃).X-ray diffraction analysis result confirmed their netlike supramolecular structures formed through the hydrogen bonding and the electrostatic attraction. The NMR chiral recognition study indicated 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-alkyl-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 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 applied as a highly efficient and reusable system for the direct enantioselective Michael addition of ketones to nitroalkenes with 70~97% yields and up to 99% ee enantioselectivities obtained. The complex system and the resulting freely dissociable anion were considered 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 tandem reactions of α,β-unsaturated aldehydes and 2-hydroxybenzaldehyde to form the chiral benzopyran derivatives as well. The desired products were S configuration escess.

KEY WORDS: ionic chiral amines, chiral amine-thioimidazoles, chiral recognition, asymmetric Michael addition, asymmetric Michael-aldol tandem reaction