一种由钙离子参与的光学拆分

将外消旋体解析成纯对映异构体的方法很多，有化学拆分法、酶拆分法、薄层拆分法和高效液相拆分法等。其中化学拆分法应用历史比较悠久。对于特定外消旋体只要能找到合适的拆分剂和溶剂，就可以通过结晶或诱导结晶的途径将外消旋体解析。不过用于化学拆分的拆分剂并不多见...     

“Dutch”拆分研究进展

本文综述了第一代Dutch拆分、第二代Dutch拆分及反义Dutch拆分的拆分机理和研究进展,并展望了Dutch拆分的应用前景。Dutch拆分能以高收率和近于100％ee值与所有的实验消旋体迅速形成非对映体的结晶。第一代Dutch拆分中Family拆分试剂在形成非对映体晶体过程是典型的固溶体行为。在第二代Dutch拆分中,成核抑制剂改变了非对映异构体的亚稳区宽度,溶解度较大的非对映体盐比溶解度较小的非对映体盐的结晶温度下降得更多,使溶解度较小的非对映体盐更容易析出。     

高效液相色谱手性固定相的研究Ⅴ——二肽叔丁酰胺型手性固定相拆分α-氨基酸、二茂铁基氨基酸及二肽衍生物对映异构体

 ]本文应用高效液相色谱(L，L)-二肽叔丁酰胺型键合硅胶手性固定相拆分N-乙酰基--氨基酸甲酰、N-乙酰基--二茂铁基丙氨酸乙酯及N-叔丁氧羰驶基亮氨酰亮氨酸甲酯等对映异构体、结果表明：部分固定相对氨基酸衍生物对映异构体有拆分效果；大部分固定相对二茂铁基丙氨酸衍生物对映异构体有较好拆分效果；所有固定相对由（D，D）-及（L，L）-亮氨酰亮氨酸衍生物构成的外消旋体均有良好的拆分效果，分离系数最高达1.79。本文对部分化合物对映异构体的拆分机制进行了初步探讨。     

天然冰片新手性化合物的合成及其晶体结构

利用天然丰产的手性助剂冰片醇与5-羟基-2(5H)-呋喃酮反应得到液体的5-冰片氧基-2(5H)-呋喃酮差向异构体混合物,后者通过硫酚的不对称Michael加成反应,得到固体的非对映异构体混合物.进一步采用分步结晶拆分的方法,得到了光学纯新的冰片手性化合物,de>98%.通过X-射线四圆衍射确定了其立体化学绝对构型.此方法的成功为天然手性助剂的利用,为液体差向异构体混合物制备光学纯非对映体化合物提供了一条新的有效途径.     

胺类拆分剂从水溶液中拆分外消旋有机酸的研究

具有光学活性的化学物质目前已在药物、食品、饮料、农药等领域得到了广泛的应用,需求日益增长,但化学合成的产物多为无活性的外消旋体(混合物、化合物或固体溶液),要从中得到单一对映体必须进行拆分,非对映体盐结晶法是目前工业应用最广泛的一种拆分技术,其原理是采用一种光学活性物质与外消旋体反应生成一对非对映立体异构体,依据两者在特定溶剂中的溶解度差异实现拆分.该技术尤其适合于外消旋的有机酸、有机碱的拆分,有关这方面拆分实例的报道较多[1～3].但迄今为止,还没有该技术系统的规律性研究报道.本文以若干外消旋有机酸为对象,试图通过以水为溶剂的拆分实验研究,探讨有机酸拆分过程的特性,从而为非对映体盐结晶拆分技术规律性的研究及外消旋有机酸拆分过程工业化的实施创造条件.     

用循环拆分法制备手性萘乙胺

研究了1-(1-萘基)乙胺[(RS)-1]和1-(2-萘基)乙胺[(RS)-2]的循环拆分方法。以D-酒石酸为拆分剂,分别拆分(RS)-1和(RS)-2得到了(R)-1-(1-萘基)乙胺(收率31%,98%ee)和(R)-1-(2-萘基)乙胺(收率30%,98%ee),并对母液中的非目标对映异构体成功的进行了消旋化,实现了循环拆分。     

经非对映异构盐的外消旋体拆分实用方法

经非对映异构盐拆分外消旋体的经典拆分方法，仍是提供对映纯化合物的有效方法之一。然而对许多外消旋体来讲，获得需要的异构体远小于50%。如何通过经典拆分使需要的异构体获得最大产率？本文阐述了一种外消旋体拆分的实用方法，通过非对映异构盐的形成可得到所需的异构体最大产率。运用该实用策略，在拆分外消旋哌啶甲酸乙酯、Corey内酯和石杉碱甲中间体上都成功实现。该策略的实践基础是著名的Marckwald 原理。     

色谱分离条件对己唑醇对映体手性拆分的影响

在自制的直链淀粉-三(苯基氨基甲酸酯)手性固定相上,成功地拆分了己唑醇对映异构体,系统研究了色谱分离条件对手性拆分的影响．结果发现,流动相中醇的结构及浓度对己唑醇对映异构体的手性拆分均有影响．在所研究温度范围15～40℃内,己唑醇对映体的In α与1／T关系呈非线性关系,分离温度在15～30℃内,其手性拆分过程受熵控制;分离温度在30～40℃内,其手性拆分过程受焓控制．     

溶剂诱导聚合物结晶的研究进展

溶剂诱导结晶(SINC)又称为液体诱导结晶,它是结晶性高聚物在溶剂(或包括其蒸汽)作用下,在低于通常Tg下诱导结晶,而在高于通常Tg时能加速结晶的现象。本文主要对溶剂诱导结晶的机理、动力学和形态学进行了讨论。     

石英晶体微天平用于预测非对映体盐结晶分离手性扁桃酸的分离效率

研究了以石英晶体微天平(QCM)手性识别结果预测手性选择剂对外消旋物的手性识别能力的新方法。经过两步组装方式将手性选择剂L-苯丙氨酸(L-Phe)组装到QCM电极表面。通过检测电极共振频率、接触角和X射线光电子能谱的变化对组装结果进行了表征。应用蒸气扩散分子组装(VDMA)方式检测L-Phe修饰QCM电极对L-扁桃酸(MA)的手性识别能力,其手性识别选择性系数约为8。随后用L-Phe作为拆分剂试验了非对映体盐结晶法拆分手性扁桃酸,并优化了手性拆分条件。结果显示,以L-Phe作为拆分剂进行非对映体盐结晶法拆分手性扁桃酸的结果与QCM手性识别结果高度吻合,表明QCM手性识别可用作辅助筛选和预测非对映体盐结晶手性拆分法的手性拆分剂。     

A practical synthesis of 3-ethyl-l-norvaline

An efficient process for the synthesis of 3-ethyl-l-norvaline has been developed. The route makes use of a Strecker reaction, whereby (S)-(−)-α-methylbenzylamine acts as a chiral auxiliary to provide nearly diastereomerically pure α-amino nitrile. Crystallization-induced asymmetric transformation enhances the yield and diastereomeric ratio and allows for efficient isolation of the product. The amino nitrile intermediate is converted to enantiomerically pure 3-ethyl-l-norvaline in three steps.     

Benzosiloles with Crystallization-Induced Emission Enhancement of Electrochemiluminescence: Synthesis,Electrochemistry, and Crystallography

Crystallization-induced emission enhancement (CIEE) was demonstrated for the first time for electrochemilunimescence (ECL) with two new benzosiloles. Compared with their solution, the films of the two benzosiloles gave CIEE of 24 and 16 times. The mechanism of the CIEE-ECL was examined by spooling ECL spectroscopy, X-ray crystal structure analysis, photoluminescence, and DFT calculations. This CIEE-ECL system is a complement to the well-established aggregation-induced emission enhancement (AIEE) systems. Unique intermolecular interactions are noted in the crystalline chromophore. The first heterogeneous ECL system is established for organic compounds with highly hydrophobic properties.     

Efficient crystallization-induced dynamic resolution of alpha-substituted carboxylic acids

Herein we present a novel route to enantiomerically enriched chiral alpha-substituted carboxylic acids by crystallization-induced dynamic resolution (CIDR) of their diastereomeric salts with chiral amines. Thus, the racemic alpha-bromo acid 3 is converted reliably with (1R,2S)-2-amino-1,2-diphenylethanol in the presence of a catalytic amount of tetrabutylammonium bromide into its R-enantiomer 4 in 90% yield with 88% ee. Similarly, the racemic alpha-thiobenzoyl acid 5 could be resolved to 90% ee in 74% yield. Further enrichment to enantiomeric homogeneity could be achieved in both cases by crystallization. In a telescoped, two-step process, S-alpha-thiobenzoyl acid 6 (>or=99.6% ee) was prepared from the racemic bromide 3 in 63% yield. State-of-the-art parallel experimentation enabled rapid screening for suitable dynamic resolution conditions. Kinetic studies defined the influence of temperature, tetrabutylammonium bromide concentration, molarity, and solvent polarity on the resolution rate, product yield, and enantiomeric excess.     

Dynamic kinetic resolution of 1-substituted-3-methyl-3-phospholene oxides via the formation of diastereomeric alkoxyphospholenium salts

A dynamic kinetic resolution method based on the formation of covalent diastereomeric intermediates was elaborated for the preparation of enantiomerically enriched 1-substituted-3-methyl-3-phospholene oxides. The 3-phospholene oxides were first converted to the corresponding chloro-3-phospholenium chlorides. The dynamic interconversion between the enantiomers of the chlorophospholenium salts was verified experimentally, as it is the key step for a dynamic resolution. The cyclic chlorophospholenium salts were reacted with a chiral auxiliary bearing a hydroxy function to form the corresponding diastereomeric alkoxyphospholenium salts in unequal amounts. The diastereomeric species then rearranged into the corresponding optically active 3-phospholene oxides upon heating. After a screening of chiral auxiliaries and the optimization of the reaction conditions, several scalemic 1-aryl- or 1-alkyl-3-methyl-3-phospholene oxides were prepared in excellent yields and with ee-s up to 35%. The key steps of this resolution were investigated by quantum chemical calculations to get some insights into the factors responsible for the stereoselection.     

Routes toward enantiopure 2-substituted indolines: an overview

Chiral-2-substituted indolines are an important class of compounds with numerous applications in organic synthesis and as constituents of a number of biologically active molecules. Consequently, there has been a continued interest in the development of efficient methods for the syntheses of this class of chiral compounds. In this review, a detailed survey of the important efforts toward the synthesis of enantioenriched 2-substituted indolines by means of the kinetic resolution or the use of a chiral auxiliary in stoichiometric or catalytic processes is provided. The resolution of racemic mixtures through diastereomeric separation is not considered in the article.     

Enantioselective decarboxylation of beta-keto esters with Pd/amino alcohol systems: successive metal catalysis and organocatalysis

The kinetics and mechanisms of one-pot cascade reactions of racemic beta-keto esters to give chiral ketones in the presence of Pd/C-chiral amino alcohol catalyst systems were studied. Transformation of 2-methyl-1-tetralone-2-carboxylic acid benzyl ester (1) into 2-methyl-1-tetralone (4) in the presence of Pd/C and cinchona alkaloids or ephedrine was chosen as a model reaction. After the first reaction step, the Pd-catalysed debenzylation of 1 to afford the corresponding beta-keto acid (2), there are two possible reaction routes that may be catalysed by the chiral amino alcohol in solution or by Pd(0) sites on the metal surface in cooperation with the adsorbed amino alcohol. The reaction intermediate 2 was synthesized, and the kinetics of decarboxylation were followed by NMR, UV and IR spectroscopy. The studies revealed that the role of Pd is to trigger the reaction series by deprotection of 1. The subsequent dominant reaction route from the racemic beta-keto acid 2 to the chiral ketone 4 is catalysed by the chiral amino alcohol in the liquid phase. It is shown that kinetic resolution of the diastereomeric salt of rac-2 and the chiral amino alcohol plays a key role in the enantioselection. High enantioselectivity necessitates an amino alcohol/rac-2 ratio of at least 2. A high ratio favours the formation of 1:1 amino alcohol/acid diastereomeric complexes, and the second amino alcohol molecule may be responsible for the enantioselective protonation of 2 in the diastereomeric complex.     

Dynamic thermodynamic and dynamic kinetic resolution of 2-lithiopyrrolidines

Dynamic resolution has been studied as a method for the asymmetric synthesis of 2-substituted pyrrolidines. Highly enantioselective electrophilic substitutions of racemic 2-lithiopyrrolidines in the presence of a chiral ligand have been achieved. The organolithium compounds were prepared by tin-lithium exchange from the corresponding tributylstannanes and n-butyllithium or by deprotonation of N-(tert-butyloxycarbonyl)pyrrolidine with sec-butyllithium. A range of N-substituents and chiral ligands were investigated for the dynamic resolution. Electrophilic quench of the resolved diastereomeric 2-lithiopyrrolidine-chiral ligand complexes provided the enantiomerically enriched 2-substituted pyrrolidines. With N-alkyl derivatives, the resolution occurs conveniently at (or just below) room temperature and either enantiomer of the product can be formed by appropriate choice of the chiral ligand. The asymmetric induction occurs as a result of a thermodynamic preference for one of the diastereomeric complexes. The minor complex was found to have a faster rate of reaction with the electrophile. The use of N-allylic derivatives provides a means to prepare the N-unsubstituted pyrrolidine products. Best results were obtained with the N-2,3-dimethylbut-2-enyl derivative, and this N-substituent could be cleaved using 1-chloroethyl chloroformate. With N-Boc-2-lithiopyrrolidine, the enantioselectivity arises by a kinetic resolution and high levels of asymmetric induction in the presence of excess n-butyllithium can be obtained. Dynamic kinetic resolution of the N-Boc derivative is limited in the scope of electrophile that can be used.     

Preparation of two new liquid chromatographic chiral stationary phases based on diastereomeric chiral crown ethers incorporating two different chiral units and their applications

Two new liquid chromatographic chiral stationary phases based on diastereomeric chiral crown ethers incorporating two different chiral units such as optically active 3,3'-diphenyl-1,1'-binaphthyl and tartaric acid unit were prepared. Between the two CSPs, one was much superior to the other especially in the resolution of tocainide and its analogues (for example, in the resolution of tocainide the separation factor, alpha, was 4.26 vs. 1.00 on the two CSPs). From these results, the two chiral units composing the two diastereomeric chiral crown ether moieties of the stationary phases were expected to show "matched" or "mismatched" effect on the chiral recognition according to their stereochemistry. The different chiral recognition abilities of the two CSPs were rationalized by the different three-dimensional structures of the two diastereomeric chiral crown ethers.     

A new class of versatile chiral-bridged atropisomeric diphosphine ligands: remarkably efficient ligand syntheses and their applications in highly enantioselective hydrogenation reactions

A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann coupling reaction of the biaryl diphosphine dioxides is featured by highly efficient central-to-axial chirality transfer with diastereomeric excess >99%. This substrate-directed diastereomeric biaryl coupling reaction is unprecedented for the preparation of chiral diphosphine dioxides, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure diphosphine ligands. The effect of chiral recognition was also revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of the chiral tether. The enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied to the catalytic enantioselective hydrogenations of alpha- and beta-ketoesters (C=O bond reduction), 2-(6'-methoxy-2'-naphthyl)propenoic acid, alkyl-substituted beta-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been attained for the catalytic reactions. In addition, the significant ligand dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N-heteroaromatic compounds were also revealed.     

Application of (1S,2S)- and (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate to the indirect enantioseparation of racemic proteinogenic amino acids

The application of (1S,2S)- or (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate as a new chiral derivatizing agent for the resolution of compounds possessing an amino group is described. The reagent is easily accessible in both enantiomeric forms after a simple two-step synthesis. Its applicability was demonstrated on the example of the resolution of a series of alpha-amino acids. The diastereomeric thiourea derivatives produced were separated by reversed-phase high-performance liquid chromatography. The effects of pH, temperature and reagent excess on the derivatization kinetics were investigated, as were the effects of pH and organic modifier on the separation.