平面手性二茂铁的合成及其在不对称催化反应中应用 的最新进展

平面手性二茂铁由于其独特的立体结构和电子效应,在不对称催化反应中已成为一类优良的手性配体。合成高光学纯度的平面手性二茂铁已受到高度重视,将成为设计、合成手性配体研究以及应用中的热点之一。本文综述了近年来其合成方法及其在不对称催化反应中应用研究的进展。     

Resolution of Cycloplatinated Ferrocenylketimines

Ferrocene derivatives especially the chiral and optically active 1,2-disubstituted ferrocenes are the most extensively investigated metallocenes. The common way to obtain the planar chirality in the ferrocene moiety is the usage of a chiral precursor. Sokolov et al have reported the asymmetric cyclopalladation with the salts of optically active carboxylic acids as nucleophilic catalysts, however, this method was suitable only when the reaction experienced the diastereomeric transition states^[1]. The only report,of the resolution of cyclometallated ferrocene derivatives was given by Nonoyama and his coworkers^[2]. They resolved dimethyl-aminomethylferrocene to optically pure enantiomers using the (S)-proline as chiral auxiliary and separated the diastereomers by solubility difference.     

Catalytic asymmetric synthesis of ferrocenes and P-stereogenic bisphosphines

The catalytic asymmetric synthesis of planar chiral ferrocenes and P-stereogenic phosphines and bisphosphines (important classes of chiral ligands for metal-catalyzed asymmetric processes) is successfully demonstrated using n-BuLi or s-BuLi in combination with substoichiometric quantities (0.1-0.5 equiv) of (-)-sparteine or the (+)-sparteine surrogate.     

Allylic Imidate Rearrangements Catalyzed by Planar Chiral Palladacycles

The discovery that palladacycles are efficient catalysts for the allylic imidate rearrangement has resulted in the successful application of several such complexes to this reaction based on planar chiral iron and cobalt containing metallocenes. These palladacycles enable the efficient and highly enantioselective synthesis of a wide variety of protected allylic amines, which are valuable building blocks for use in asymmetric synthesis.     

Comparative analysis of chiral drugs in view of chemometrics

With the development of methods for obtaining chiral compounds as potential drugs, there is also need to develop analytical methods for the separation of both enantiomers. Keeping in mind that the physical and chemical properties of both enantiomers are identical, their different nature will only be revealed in a chiral environment that is appropriately designed. Physicochemical systems can be used to predict the differences in biological activity of both enantiomers. The complexity of the problem requires the use of additional tools, which are various chemometric methods. This paper reviews the application of chemometry in the analysis of chiral drugs and discusses the effects of a combination of chromatographic, electrophoretic, and spectroscopic analysis (UV-Vis absorption spectroscopy, and near-IR spectroscopy aided by cyclodextrin inclusion complexes) with chemometrics for improving the methods of enantioseparation (experimental design), explaining the mechanisms of behavior and chiral recognition (quantitative structure-enantioselective retention relationships) and indicating chiral purity (enantiomeric excess).     

Chiral separation of quinolones by liquid chromatography and capillary electrophoresis

The quinolones are derivatives of oxoquinolines and mostly known for their antibacterial and antiviral activities. Many quinolones are chiral compounds having asymmetric centers and important due to their enantioselective biological activities. In order to study the biological activities of quinolone enantiomers, to control the manufacturing of homochiral drugs and to prepare necessary quantities of pure enantiomers for preclinical or clinical trials, respective chiral separation methods are urgently needed. In this context, the present review discusses chromatographic and electrophoretic methods for the enantioseparation of chiral quinolones and provides some useful information on their physical and pharmaceutical properties. The drawbacks of currently used techniques are revealed and ways to overcome them are outlined. Moreover, recommendations for an optimal choice of a separation protocol are given.     

PdII‐Catalyzed Regio‐ and Enantioselective Oxidative C−H/C−H Cross‐Coupling Reaction between Ferrocenes and Azoles

Asymmetric C?H bond functionalization reaction is one of the most efficient and straightforward methods for the synthesis of optically active molecules. Herein we disclose an asymmetric C?H/C?H cross‐coupling reaction of ferrocenes with azoles such as oxazoles and thiazoles. Palladium(II)/monoprotected amino acid (MPAA) catalytic system which exhibits excellent reactivity and regioselectivity for oxazoles and thiazoles. This method offers a powerful strategy for constructing planar chiral ferrocenes. Mechanistic studies suggest that the C?H bond cleavage of azoles is likely proceeding through a S_EAr process and may not be a turnover limiting step.     

毛细管电泳新型手性分离体系研究进展

在现代分离科学中,手性化合物的分离分析一直是研究的重点和难点。相比于高效液相色谱（HPLC）、气相色谱（GC）等传统色谱分析方法,毛细管电泳（CE）技术凭借其高效率、低消耗、分离模式多样化等诸多优势,已经发展成为手性分离研究领域最有应用前景的分析方法之一。近年来,研究人员在CE手性分析方法的构建过程中,基于毛细管电动色谱（EKC）、配体交换毛细管电泳（LECE）、毛细管电色谱（CEC）等各种基础电泳模式,不断地对传统手性分离体系进行优化和改造,构建出了许多高性能的新型手性CE分离体系。如利用各类功能化离子液体以"手性离子液体协同拆分""手性离子液体配体交换""离子液体手性选择剂"等模式设计出多种基于离子液体的CE手性分离体系;利用纳米材料独特的尺寸效应、多样性、可设计性等特点,直接或与传统手性选择剂有机结合构建CE手性分离体系。此外,金属有机骨架材料修饰、低共熔溶剂修饰、非连续分段式部分填充等各式新颖的CE手性分离体系也都被研究人员成功开发,并表现出较大的发展潜力。该综述将对近年来（尤其是2015~2019年）此类新型CE手性分离体系的发展状况进行梳理,并结合相应的手性识别机理研究和手性CE方法实际应用情况,对该领域存在的问题及发展前景进行分析和展望。     

1-Phosphino-2-sulfenylferrocenes as planar chiral ligands in enantioselective palladium-catalyzed allylic substitutions

The synthesis of a wide structural variety of enantiopure 1-phosphino-2-sulfenylferrocene ligands 1 possessing exclusively planar chirality is described. In the case of the readily available tert-butylsulfenyl derivatives very high enantioselectivities were obtained in the palladium-catalyzed allylic substitution of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate (ee's up to 97%) and nitrogen nucleophiles (ee's up to 99.5%). Palladium complexes of these ferrocenes were characterized by NMR and X-ray diffraction, revealing the P,S-bidentate character of the ligands 1 and the formation of a single epimer on the stereogenic sulfur atom resulting from the complexation with palladium. A model justifying the observed asymmetric induction exerted by this novel family of chiral ferrocenes, supported by solution NMR studies on a palladium allylic complex, is discussed.     

Developments of chiral metallocenes as polymerization catalysts

This review article describes developments in chiral metallocenes as polymerization catalysts focusing on C2 symmetric ansa-zirconocene complexes. Selective synthesis of rac-isomers of ansa-zirconocenes are surveyed. Isospecific polymerizations of propylene catalyzed by chiral zirconocenes are summarized. Advanced series of polymerizations by chiral metallocenes such as asymmetric polymerization and polymerization of polar monomers are also introduced.     

Recent development trends for chiral stationary phases based on chitosan derivatives,cyclofructan derivatives and chiral porous materials in high performance liquid chromatography

The separation of enantiomers by chromatographic methods, such as gas chromatography, high‐performance liquid chromatography and capillary electrochromatography, has become an increasingly significant challenge over the past few decades due to the demand of pharmaceutical, agrochemical, and food analysis. Among these chromatographic resolution methods, high‐performance liquid chromatography based on chiral stationary phases has become the most popular and effective method used for the analytical and preparative separation of optically active compounds. This review mainly focuses on the recent development trends for novel chiral stationary phases based on chitosan derivatives, cyclofructan derivatives, and chiral porous materials that include metal‐organic frameworks and covalent organic frameworks in high‐performance liquid chromatography. The enantioseparation performance and chiral recognition mechanisms of these newly developed chiral selectors toward enantiomers are discussed in detail.     

Chiral analysis of pollutants and their metabolites by capillary electromigration methods

Chiral separation of enantiomers is one of the most challenging tasks for any analytical technique including CE. Since the first report in 1985 showing the great possibilities of CE for the separation of chiral compounds, the amount of publications concerning this topic has quickly increased. Although chiral electromigration methods have mainly been used for enantioseparation of drugs and pharmaceuticals, they have also been applied to analyze chiral pollutants. This article intends to provide an updated overview, including works published till January 2005, on the principal applications of CE to the chiral analysis of pollutants and their metabolites, with special emphasis on articles published in the last 10 years. The main advantages and drawbacks regarding the use of CE for chiral separation of pollutants are addressed including some discussion on the foreseen trends of electromigration procedures applied to chiral analysis of contaminants.     

Membranes and membrane processes for chiral resolution

This critical review is devoted to an active field of research on chiral separation, membrane-based enantioseparation technique, which has potential for large-scale production of single-enantiomer compounds. Adsorption-type enantioselective membranes and membrane-assisted resolution systems with non-enantioselective solid membranes have attracted much attention recently. The principles and recent developments of both enantioselective liquid and solid membranes and membrane-assisted processes for chiral resolution will be summarized comprehensively in this review, in which the contents are of interest to a wide range of readers in a variety of fields from analytical, organic and medicinal chemistry, to pharmaceutics and materials, to process engineering for fabricating pharmaceuticals, agrochemicals, fragrances and foods, and so on (148 references).     

Ferrocene-based derivatization in analytical chemistry

Ferrocene-based derivatization has raised considerable interest in many fields of analytical chemistry. This is due to the well-established chemistry of ferrocenes, which allows rapid and easy access to a large number of reagents and derivatives. Furthermore, the electrochemical properties of ferrocenes are attractive with respect to their detection. This paper summarizes the available reagents, the reaction conditions and the different approaches for detection. While electrochemical detection is still most widely used to detect ferrocene derivatives, e.g., in the field of DNA analysis, the emerging combination of analytical separation methods with electrochemistry, mass spectrometry and atomic spectroscopy allows ferrocenes to be applied more universally and in novel applications where strongly improved selectivity and limits of detection are required.     

Toggling enantioselective catalysis--a promising paradigm in the development of more efficient and versatile enantioselective synthetic methodologies

The increasingly needed synthesis of both enantiomers of a chiral compound usually requires the use of both enantiomers of a chiral catalyst. Several of the usually employed chiral ligands are naturally available in only one enantiomeric form, the antipode often being of labor-intensive preparation. Enantiodivergent asymmetric catalysis has accrued in importance in this regard, in that it allows expeditious access to both enantiomers of a product without any direct modification on the chemical structure of the chiral promoter. Various promising examples will be discussed throughout the review. If available or envisageable, a mechanistic rationale for the observed enantioinversion will be outlined.     

Catalytic enantioselective synthesis of axially chiral allenes

The conventional procedures for preparing optically active axially chiral allenes generally require stoichiometric chiral sources as either substrates or reagents. On the other hand, examples of catalytic asymmetric synthesis of axially chiral allenes are rare and it is a relatively underdeveloped area in synthetic organic chemistry. In this review article, various methods for preparing enantiomerically enriched axially chiral allenes using substoichiometric chiral sources are surveyed. Some reactions with stoichiometric but recoverable chiral sources are also mentioned. Most of the asymmetric reactions in these categories are transition-metal-catalyzed reactions, and there are a few examples of organocatalytic reactions. In addition, some enzymatic/microbial systems are also known.     

Chiral ionic liquids,a renewal for the chemistry of chiral solvents? Design,synthesis and applications for chiral recognition and asymmetric synthesis

Chiral ionic solvents were almost unexplored before the last five years. This field which is of increasing importance could constitute a renewal for the chemistry of chiral solvents. So far reported examples are designed either from the chiral pool (aminoacids, hydroxyacids, amines, aminoalcohols, terpenes and alkaloids) or by asymmetric synthesis; they can bear central, axial or planar chirality. Modern applications in asymmetric synthesis, enzymatic chemistry, chiral chromatography and NMR are surveyed. Their use in the field of liquid crystals and for stereoselective polymerisation are also discussed. At the end of the article, a series of tables is compiled including all the CILs described to date and their physical properties.     

Chiral separation and quantitation of cetirizine and hydroxyzine by maltodextrin-mediated CE in human plasma: effect of zwitterionic property of cetirizine on enantioseparation

In the present study, a very simple CE method for chiral separation and quantitation of zwitterionic cetirizine (CTZ), as the main metabolite of hydroxyzine (HZ), and HZ has been developed. In addition, the effect of zwitterionic property of CTZ on enantioseparation was investigated. Maltodextrin, a linear polysaccharide, as a chiral selector was used and several parameters affecting the separation such as pH of BGE, concentration of chiral selector and applied voltage were studied. The best BGE conditions for CTZ and HZ enantiomers were optimized as 75 mM sodium phosphate solution at pH of 2.0, containing 5% w/v maltodextrin. Results showed that, compared to HZ, pH of BGE was an effective parameter in enantioseparation of CTZ due to the zwitterionic property of CTZ. The linear range of the method was over 30-1200 ng/mL for all enantiomers of CTZ and HZ. The quantification and detection limits (S/N=3) of all enantiomers were 30 and 10 ng/mL, respectively. The method was used to quantitative enantioseparation of CTZ and HZ in spiked human plasma.     

毛细管电泳在手性化合物分离中的应用进展

由于手性化合物尤其是手性药物的两个对映体具有不同的化学性质和生理活性,对手性化合物进行分离在医药、生物、食品和环境等领域都具有十分重要的意义。毛细管电泳由于其独特的优势已广泛应用于手性物质的分离。本文对2013~2015年毛细管电泳用于手性分离的最新进展进行了综述,并对其发展前景进行了展望。     

Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods

Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual.