Asymmetric Electrochemical Transformations

The field of electrochemical synthesis has developed rapidly over the last decade and has provided alternative synthetic methods with the absence of stoichiometric amounts of chemical oxidants or reductants. Although sustainable electrosynthetic procedures have been developed, relatively few examples of highly enantioselective catalytic electrosynthesis have been reported to date. The development of general strategies for electrochemical enantiocontrol has thus proven to be a considerable challenge. This Minireview highlights the current knowledge and recent advances in the synthetic utility of electrochemical transformations for asymmetric synthesis. Specifically, three major types of catalytic enantioselective strategy in electrosynthesis are outlined, including electrochemical activation of chiral catalyst‐bound substrates, asymmetric cascade electrochemical processes, and chemically modified chiral electrodes.     

Enantioselective Nanoporous Carbon Based on Chiral Ionic Liquids

One of the greatest challenges in modern chemical processing is to achieve enantiospecific control in chemical reactions using chiral media such as chiral mesoporous materials. Herein, we describe a novel and effective synthetic pathway for the preparation of enantioselective nanoporous carbon, based on chiral ionic liquids (CILs). CILs of phenylalanine (CIL(Phe)) are used as precursors for the carbonization of chiral mesoporous carbon. We employ circular dichroism spectroscopy, isothermal titration calorimetry (ITC), and chronoamperometry in order to demonstrate the chiral nature of the mesoporous carbon. The approach presented in this paper is highly significant for the development of a new type of chiral porous materials for enantioselective chemistry. In addition, it contributes significantly to our understanding of the structure and nature of chiral nanoporous materials and surfaces.     

The Electron Spin as a Chiral Reagent

We show that enantioselective reactions can be induced by the electron spin itself and that it is possible to replace a conventional enantiopure chemical reagent by spin‐polarized electrons that provide the chiral bias for enantioselective reactions. Three examples of enantioselective chemistry resulting from electron‐spin polarization are presented. One demonstrates the enantioselective association of a chiral molecule with an achiral self‐assembled monolayer film that is spin‐polarized, while the other two show that the chiral bias provided by the electron helicity can drive both reduction and oxidation in enantiospecific electrochemical reactions. In each case, the enantioselectivity does not result from enantiospecific interactions of the molecule with the ferromagnetic electrode but from the polarized spin that crosses the interface between the substrate and the molecule. Furthermore, the direction of the electron‐spin polarization defines the handedness of the enantioselectivity. This work demonstrates a new mechanism for realizing enantioselective chemistry.     

Poly(pyrroles) containing chiral side chains: effect of substituents on the chiral recognition in the doped as well as in the undoped state of the polymer film

The chiral discrimination of different poly(pyrroles) grafted by chiral side chains was investigated both in the doped and undoped state of the polymer films. To verify the enantioselective properties in the doped state, cyclic voltammograms were recorded in acetonitrile in the presence of the enantiomers of camphorsulfonic acid and the potentiodynamic polymerization of the appropriate monomers was performed using the same chiral electrolytes. The enantiomericrecognition in the undoped state was investigated by the application of these modified electrode surfaces in the enantioselective electroreduction of the prochiral ketones 4-methyl benzophenone and 2,5-dimethyl benzophenone. One polymer exhibits a recognition ability in the doped state; the investigation for the undoped state is in progress. A second polymer does not show enantioselective properties either in the doped nor in the undoped state. Electronic Publication     

介孔二氧化硅对映选择性吸附的手性印迹调控

使用手性阴离子表面活性剂作为超分子模板, 采用共结构导向法制备手性介孔二氧化硅(CMS), 并运用圆二色谱(CD)对CMS对映选择性吸附结果进行检测, 比较了有无共结构导向剂(CSDA)在介孔表面的排列对吸附选择性的影响. 结果表明, 当使用构型相反的手性超分子模板剂对原合成CMS材料的介孔内表面进行修饰时, 可诱导结构共导向剂N?三甲氧基硅基丙基?N, N, N?三甲基氯化铵(TMAPS)发生手性相反的排列进而导致完全相反的对映选择性吸附. 实验证明此方法合成的CMS的对映选择性吸附及分离能力主要是由修饰在介孔表面的TMAPS螺旋排列形成的手性印迹所导致. 此手性超分子模板诱导TMAPS手性印迹的策略具有一定的普适性, 可对原合成介孔材料对映选择性吸附进行原位调控, 对于拓展其在立体选择性识别、 不对称催化及药物输送等方面的应用具有一定的指导意义.     

Asymmetric heterogeneous carbene transfer catalyzed by optically active ruthenium spirobifluorenylporphyrin polymers

Anodic oxidation of chiral ruthenium complexes of spirobifluorenylporphyrins leads to the coating of the working electrode by insoluble optically active films whose electrochemical behaviour and physicochemical properties are described. After removal from the electrode, the ruthenium-complexed polymers were evaluated as enantioselective catalysts for the cyclopropanation of olefins by ethyl diazoacetate. The results show the reactions proceeded very efficiently at room temperature with excellent yields (80–90%) and moderate enantioselectivities (up to 53% at −40 °C). The chiral electrosynthesized polymer catalysts can be recycled by simple filtration and reused even up to the seventh cycle with only a slight decrease of activity and enantioselectivity.     

Chiral recognition applications of molecularly imprinted polymers: a critical review

Molecular imprinting technology offers the unique opportunity to tailor chiral stationary phases with predefined chiral recognition properties by employing the enantiomers of interest as binding-site-forming templates. Added advantages, such as ease of preparation, chemical robustness, low-cost production, and the possibility of shaping molecularly imprinted polymers (MIPs) in various self-supporting formats, render them attractive materials for a broad range of chiral recognition applications. In this review a critical overview on recent developments in the field of MIP-based chiral recognition applications is given, focusing on separation techniques and molecular sensing. Inherent limitations associated with the use of enantioselective MIP materials in high-performance separation techniques are outlined, including binding site heterogeneity and slow mass transfer characteristics. The prospects of MIP materials as versatile recognition elements for the design of enantioselective sensor systems are highlighted.     

Highly Enantioselective Adsorption of Small Prochiral Molecules on a Chiral Intermetallic Compound

Intrinsically chiral surfaces of intermetallic compounds are shown to be novel materials for enantioselective processes. Their advantage is the significantly higher thermal and chemical stability, and therefore their extended application range for catalyzed chiral reactions compared to surfaces templated with chiral molecular modifiers or auxiliaries. On the Pd₁‐terminated PdGa(111) surface, room‐temperature adsorption of a small prochiral molecule (9‐ethynylphenanthrene) leads to exceptionally high enantiomeric excess ratios of up to 98 %. Our findings highlight the great potential of intrinsically chiral intermetallic compounds for the development of novel, enantioselective catalysts that can be operated at high temperatures and potentially also in harsh chemical environments.     

Combinatorial chemistry approach to chiral catalyst engineering and screening: rational design and serendipity

An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune-not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach.     

Novel molecularly imprinted microsphere using a single chiral monomer and chirality-matching (S)-ketoprofen template

We designed and synthesized a cinchonine derivative to be used as a novel chiral monomer. It was employed in a dual role of functional monomer and cross-linking monomer, displaying multi-binding sites for the template (S)-ketoprofen. Monodisperse molecularly imprinted core-shell microspheres were prepared using surface imprinting method on silica gel. The results show a substantial synergistic effect in the enantioselective recognition, confirming our initial hypothesis. Computational simulation of the monomer and template pre-arrangement strongly supports our proposed chiral recognition mechanism for the imprinted microspheres.     

Molecular-level functionalization of electrode surfaces. An overview

Electrochemical reactions occur at electrode/electrolyte interfaces. Hence, manipulation and design of electrochemical interfaces accompanied by surface modifications have assumed vital importance. Molecular level modification, either at the monolayer or multilayer level of electrode surfaces and leading to functionalization of electrodes, is being actively pursued by researchers. Modification based on the self-assembled monolayer approach has enabled electrodes to acquire molecular recognition and molecular electronic characteristics. Functionalization of electrode surfaces using polymeric materials and enzymes has facilitated electrodes in exhibiting properties like catalysis, molecular recognition, electrochromism and birefringence. The results of such molecular level functionalization studies of electrode surfaces carried out recently in our laboratories are presented in this overview. Besides, some representative results reported from elsewhere are also included.     

Heterogeneous Enantioselective Catalysis with Chiral Encoded Mesoporous Pt−Ir Films Supported on Ni Foam

The development of heterogeneous catalysts for asymmetric synthesis is one of the most challenging topics in chemistry, as it allows obtaining enantiomerically pure compounds. Recently, metal layers incorporating molecular chiral cavities, obtained by electroreduction of a metal source in the simultaneous presence of a non-ionic surfactant and asymmetric molecules, have been proposed for a wide range of applications, including enantioselective electroanalysis and electrosynthesis, as well as chiral separation. In contrast to this previous work, solely based on electrochemical phenomena, herein we designed and employed nanostructured chiral encoded Pt−Ir alloys, supported on high surface area nickel foams, as heterogeneous catalysts for the asymmetric hydrogenation of aromatic ketones. Fine-tuning the experimental conditions allows achieving very high enantioselectivity (>80%), combined with improved catalyst stability.     

Recent developments in the synthesis and functionalization of conducting poly(thiophenes)

The mechanism of the electropolymerization of thiophene derivatives has been investigated by varying the electrosynthesis conditions and the monomer structure. The results of these analyses led to the definition of optimized electrosynthesis conditions allowing the control of the electrical and electrochemical properties of poly(thiophenes). On the basis of these results, the properties of these polymers have been modified by means of a new one-step electrosynthesis of conducting composite materials and by the direct electropolymerization of tailor-made functionalized monomers. For this purpose, the steric conditions associated to the various possibilities of covalent derivatization have been analyzed, leading to the definition of a “functionalization space”, compatible with the preservation of high conductivity and electrochemical reversibility in the resulting polymers. This concept has been applied to the synthesis of highly conducting chiral poly(thiophenes) on which an effect of enantioselective molecular recognition has been demonstrated for the first time.     

Enantioselective sensor based on microgravimetric quartz crystal microbalance with molecularly imprinted polymer film

We report a novel quartz crystal microbalance sensor that provides enantioselectivity to dansylphenylalanine enantiomers by using a molecularly imprinted polymer film as a recognition element. The polymeric recognition thin film, imprinted with chiral dansyl-L-phenylalanine, was immobilised on a gold electrode modified with a photoactive precursor monolayer via a self-assembly process using photopolymerization. The fabricated sensor was able to discriminate between L- and D-dansylphenylalanine enantiomers in solution owing to the enantioselectivity of the imprinted sites. The enantiomeric composition of L- and D-enantiomeric mixtures could be quantitatively determined by the fabricated sensor. The detection limit is 5 micrograms mL-1 with a response range of 5-500 micrograms mL-1 at pH 10.0. The influence of the template concentration on the sensitivity and selectivity of the synthesised polymer membranes was investigated and optimised. The surface characteristics of the polymer coating were studied by varying the pH value of the buffer solution, and a convenient regeneration process was proposed to increase the reproducibility and reusability of the sensor by flushing with pH 2.0 buffer. The selectivity and recognition mechanism of the imprinted polymer film were studied with compounds that are structurally related to the template. The method presented in this work provides a novel means of preparing highly selective and sensitive chemical sensors via self-assembly and molecularly imprinting techniques.     

Separation of tryptophan enantiomers with molecularly imprinted polypyrrole electrode column

<正>In this study,we have fabricated molecularly imprinted polypyrrole(PPy) packed electrode columns and investigated their effects on separation of tryptophan(Trp) enantiomers by using potential control.The results indicate that the imprinted PPy electrode columns could efficiently enhance the L-Trp uptake and separate Trp enantiomers effectively,implying the great potential for the enantioselective recognition of other amino acids enantiomers.     

Enantioselective surface chemistry of R-2-bromobutane on Cu(643)R&S and Cu(531)R&S

The enantioselective surface chemistry of chiral R-2-bromobutane was studied on the naturally chiral Cu(643)R&S and Cu(531)R&S surfaces by comparing relative product yields during temperature-programmed reaction spectroscopy. Molecularly adsorbed R-2-bromobutane can desorb molecularly or debrominate to form R-2-butyl groups on the surfaces. The R-2-butyl groups react further by beta-hydride elimination to form 1- or 2-butene or by hydrogenation to form butane. Temperature-programmed reaction spectroscopy was used to quantify the relative yields of the various reaction products. At low coverages of R-2-bromobutane on Cu(643)R&S and Cu(531)R&S, the surface chemistry is not enantioselective. At monolayer coverage, however, the product yields indicate that the R-2-bromobutane decomposition reaction rates are sensitive to the handedness of the two chiral surfaces. The impact of surface structure on enantioselectivity was examined by studying the chemistry of R-2-bromobutane on both Cu(643)R&S and Cu(531)R&S. The selectivity of R-2-bromobutane desorption versus debromination is enantiospecific and differs significantly from Cu(643) to Cu(531). The selectivity of the R-2-butyl reaction by beta-hydride elimination versus hydrogenation is only weakly enantiospecific and is similar on both the Cu(643) and Cu(531) surfaces. These results represent the first quantitative observations of enantioselectivity in reactions with well-known mechanisms probed using a simple adsorbate on naturally chiral metal surfaces.     

The influence of anions and kink structure on the enantioselective electro-oxidation of glucose

The electro-oxidation of glucose in sulfuric acid using well-defined chiral platinum single crystal electrodes has been demonstrated previously to be an enantioselective reaction with the degree of enantioselectivity being dependent on the surface density of kink sites. The chirality of the surface originates from the microstructure of the kink site whereby the sequence of the three fundamental adsorption sites [111], [100] and [110] constituting the kink may be viewed from the electrolyte phase either in a clockwise (R-enantiomer) or anti-clockwise (S-enantiomer) fashion. In the present study, this work is extended to examine the role of both kink structure and specifically adsorbed anions on the mechanism of chiral discrimination. Kinked surfaces based on [111] terraces (Pt[976],Pt[643] and Pt[531]),[100] terraces (Pt[721]) and [110] terraces (Pt[11,7,1] and Pt[841]) have been investigated and both the magnitude and potential dependence of the enantioselective electro-oxidation of glucose characterised. Additionally, the changes engendered by interchanging the character of the two steps whose confluence form the kink whilst maintaining the symmetry of the terrace has also been examined via a comparison of Pt[643] and Pt[431]. Low energy electron diffraction (LEED) was used to confirm that all surfaces when clean and thermally annealed were in their (1 x 1) state. Cyclic voltammetry (CV) confirmed this finding for flame-annealed electrodes after cooling in hydrogen. Three general points emerge from the electro-oxidation studies: (i) The highest degree of enantioselectivity is exhibited by kink sites adjacent to [111] and [110] terraces in sulfuric acid. (ii) The adsorption of specifically adsorbed anions like bisulfate/sulfate influences strongly the chiral discriminatory behaviour of all surfaces. (iii) No electro-oxidation takes place at [110] sites, as evidenced by complete overlap of the [110] step hydrogen underpotential deposition (UPD) charge in glucose and glucose-free solutions. Nonetheless it is deduced that [110] sites must play some part in the initial orienting of the glucose molecule prior to reaction. Ideas based on these findings are developed in order to rationalise in particular the influence of anion adsorption on the initial enantioselective interaction of the glucose molecule with the chiral surface.     

Optical resolution of racemic amino acid derivatives with molecularly imprinted membranes from tetrapetide consisting of glycinyl residues

Molecularly imprinted polymeric membranes were prepared from polystyrene resin bearing tetrapeptide of glycine. The tetrapeptide was converted into a chiral recognition site by using the d- or l-isomer of N-α-tert-butoxycarbonyltryptophan (Boc-Trp) as a print molecule. The d-isomer was incorporated into the membrane imprinted by Boc-d-Trp in preference to the corresponding l-isomer and vice versa. Those molecularly imprinted membranes showed chiral separation ability. In the enantioselective electrodialysis, the observed permselectivity corresponded to the adsorption selectivity of ca. 2.3 at the optimum potential difference of 2.0 V.     

Catalysis of electrochemical reactions at derivatized electrodes: Kinetic model for stationary voltammetric techniques and preparative scale electrolysis

Catalysis of electrochemical reactions at derivatized electrode surfaces may offer an attractive alternative to homogeneous catalysis as far as problems related to separation between catalyst and product and to minimizing the required amount of catalyst are concerned. In this context, several points are addressed regarding catalysis at a monolayer derivatized electrode: (1) catalytic efficiency in terms of preparative scale electrolysis and effect of side reactions destroying the active form of the catalyst;(2) comparison between monolayer derivatized electrode and homogeneous catalysis for systems having the same activation free energy; (3) the problem of redox (outer-sphere) catalysis at monolayer derivatized electrodes compared to naked conventional electrodes is discussed in terms of the current theories of adiabatic outer-sphere electron transfer involving the possible effects of collision frequency factors, image force energy and electrostatic work terms.