Chiral Modifier Research Articles

The Critical Role of Tilted Cinchona Surface Species for Enantioselective Hydrogenation

On chirally modified metal catalysts enantioselectivity is controlled by the molecular orientation of adsorbates at the chiral catalytic solid–liquid interface. To gain information on the surface coverage and to assess the enantioselecting ability of chiral modifiers depending on their molecular orientation, we employed an operando spectroscopic technique using attenuated total reflection IR and UV–vis spectroscopy. Our study reveals that the enantiodifferentiation of the cinchona chiral modifier cinchonine varies significantly depending on its adsorption mode. In contrast to the prevailing mechanistic models, which imply that the most stable surface species is responsible for enantiodifferentiation, our results show that less stable cinchona species with a tilted aromatic ring anchor provide significantly stronger enantioselective control. As a consequence, the so-called anchoring moiety of the chiral modifier exceeds the mere function of adsorptive anchoring and its molecular orientation has to be also ...

Application of Organic Monolithic Materials to Enantioseparation in Capillary Separation Techniques.

This review article is primarily focused on the state-of-the-art of enantioseparations on organic monolithic materials. The article gives an overview of the chiral stationary phases and its application in capillary electrochromatography (CEC), and capillary- and nano-liquid chromatography (cLC and nLC). Since thousands of publications have been emerged from 2000's and citing all these papers would extend the scope of this review; then, recent developments from last 10 years (2006 to 2016) will be mentioned. Mostly, stationary phases based on copolymers obtained from chiral functional monomers and surface modifications of organic monoliths with chiral ligands will be discussed. The effective application of these chiral separation methodologies in several analysis areas will be also included.

Structure and Dynamics of Individual Diastereomeric Complexes on Platinum: Surface Studies Related to Heterogeneous Enantioselective Catalysis.

The modification of heterogeneous catalysts through the chemisorption of chiral molecules is a method to create catalytic sites for enantioselective surface reactions. The chiral molecule is called a chiral modifier by analogy to the terms chiral auxiliary or chiral ligand used in homogeneous asymmetric catalysis. While there has been progress in understanding how chirality transfer occurs, the intrinsic difficulties in determining enantioselective reaction mechanisms are compounded by the multisite nature of heterogeneous catalysts and by the challenges facing stereospecific surface analysis. However, molecular descriptions have now emerged that are sufficiently detailed to herald rapid advances in the area. The driving force for the development of heterogeneous enantioselective catalysts stems, at the minimum, from the practical advantages they might offer over their homogeneous counterparts in terms of process scalability and catalyst reusability. The broader rewards from their study lie in the insights gained on factors controlling selectivity in heterogeneous catalysis. Reactions on surfaces to produce a desired enantiomer in high excess are particularly challenging since at room temperature, barrier differences as low as ∼2 kcal/mol between pathways to R and S products are sufficient to yield an enantiomeric ratio (er) of 90:10. Such small energy differences are comparable to weak interadsorbate interaction energies and are much smaller than chemisorption or even most physisorption energies. In this Account, we describe combined experimental and theoretical surface studies of individual diastereomeric complexes formed between chiral modifiers and prochiral reactants on the Pt(111) surface. Our work is inspired by the catalysis literature on the enantioselective hydrogenation of activated ketones on cinchona-modified Pt catalysts. Using scanning tunneling microscopy (STM) measurements and density functional theory (DFT) calculations, we probe the structures and relative abundances of non-covalently bonded complexes formed between three representative prochiral molecules and (R)-(+)-1-(1-naphthyl)ethylamine ((R)-NEA). All three prochiral molecules, 2,2,2-trifluoroacetophenone (TFAP), ketopantolactone (KPL), and methyl 3,3,3-trifluoropyruvate (MTFP), are found to form multiple complexation configurations around the ethylamine group of chemisorbed (R)-NEA. The principal intermolecular interaction is NH···O H-bonding. In each case, submolecularly resolved STM images permit the determination of the prochiral ratio (pr), pro-R to pro-S, proper to specific locations around the ethylamine group. The overall pr observed in experiments on large ensembles of KPL-(R)-NEA complexes is close to the er reported in the literature for the hydrogenation of KPL to pantolactone on (R)-NEA-modified Pt catalysts at 1 bar H2. The results of independent DFT and STM studies are merged to determine the geometries of the most abundant complexation configurations. The structures reveal the hierarchy of chemisorption and sometimes multiple H-bonding interactions operating in complexes. In particular, privileged complexes formed by KPL and MTFP reveal the participation of secondary CH···O interactions in stereocontrol. State-specific STM measurements on individual TFAP-(R)-NEA complexes show that complexation states interconvert through processes including prochiral inversion. The state-specific information on structure, prochirality, dynamics, and energy barriers delivered by the combination of DFT and STM provides insight on how to design better chiral modifiers.

Surface chemistry: Giving catalysts a hand.

Using chiral modifiers on the surfaces of heterogeneous catalysts is a potentially fruitful route to practical stereoselective chemistry. Now, a study of the dynamics of prochiral adsorbates on modified surfaces has shown that they can rapidly interconvert between adsorption states of different prochirality.

STM Study of Ketopantolactone/(R)-1-(1-Naphthyl)ethylamine Complexes on Pt(111): Comparison of Prochiral and Enantiomeric Ratios and Examination of the Contribution of CH···OC Bonding

We report a comprehensive model surface science study, using scanning tunneling microscopy (STM), of the regioselective and stereospecific complexation of a prochiral substrate molecule to a chiral modifier molecule on a metal surface. The system is chosen so as to compare the prochiral ratio (pr) measured directly by STM for the model system with the reported enantiomeric ratio (er) for the hydrogenation of the prochiral molecule using the same chiral modifier and metal under true reaction conditions. Specifically, diastereomeric complexes formed between ketopantolactone (KPL) and (R)-1-(1-naphthyl)ethylamine ((R)-NEA) on Pt(111) were studied as a function of the ratio of KPL to (R)-NEA. Only KPL molecules in complexes are detected in the STM experiments, performed between 237 and 250 K, due to rapid diffusion of free KPL on the surface. The prochirality of KPL in almost all bimolecular and termolecular, (KPL)2/(R)-NEA, complexation configurations is assigned as pro-R or pro-S using the contrast within t...

Enantioselective hydrogenation of N-heteroaromatics catalyzed by chiral diphosphine modified binaphthyl palladium nanoparticles

The first application of binaphthyl-stabilized palladium nanoparticles (Bin-PdNPs) with chiral modifiers in asymmetric hydrogenation of N-heteroaromatics is revealed.

Chiral segregation driven by a dynamical response of the adsorption footprint to the local adsorption environment: bitartrate on Cu(110).

Local or global ordering of chiral molecules at a surface is a key step in both chiral separation and heterogeneous enantioselective catalysis. Using density functional theory and scanning probe microscopy results, we find that the accepted structural model for the well known bitartrate on Cu(110) chiral system cannot account for the chiral segregation observed. Instead, we show that this strongly bound, chiral adsorbate changes its adsorption footprint in response to the local environment. The flexible adsorption geometry allows bitartrate to form stable homochiral trimer chains in which the central molecule restructures from a rectangular to an oblique footprint, breaking its internal hydrogen bonds in order to form strong intermolecular hydrogen bonds to neighbouring adsorbates. Racemic structures containing mixed enantiomers do not form strong hydrogen bonds, providing the thermodynamic driving force for the chiral separation that is observed experimentally. This result shows the importance of considering the dynamical response of molecular adsorption footprints at the surface in directing chiral assembly and segregation. The ability of strongly-chemisorbed enantiomers to change footprint depending on the local adsorption environment indicates that supramolecular assemblies at surfaces may exhibit more complex dynamical behaviour than hitherto suspected, which, ultimately, could be tailored to lead to environment and stimuli-responsive chiral surfaces.

3 D Ordered Macroporous Alumina–Carbon Nanocomposite Supported Platinum Nanoparticles as Effective and Reusable Catalysts for Asymmetric Hydrogenation

AbstractThe three‐dimensionally ordered macroporous alumina‐carbon composite materials were firstly prepared through a surfactant‐assisted colloidal crystal template method and applied to support Pt nanoparticles. The results of SEM, XRD, TEM, and N2 sorption analyses revealed that these composite materials possessed highly ordered macroporous structures with meso‐ and micropores within the skeletons of macropores and that the Pt nanoparticles were well dispersed on these materials with a very narrow size distribution. These prepared Pt nanocatalysts were evaluated in the asymmetric hydrogenation of ethyl pyruvate after chiral modification with cinchonidine. Excellent catalytic activity and enantioselectivity were achieved. More importantly, these catalysts exhibited extraordinary stability and reusability during the reaction and could be reused at least 26 times without significant loss in catalytic activity and enantioselectivity.

Reversible Plasmonic Circular Dichroism via Hybrid Supramolecular Gelation of Achiral Gold Nanorods

The fabrication of chiroptical plasmonic nanomaterials such as chiral plasmonic gold nanorods (GNRs) has been attracting great interest. Generally, in order to realize the plasmonic circular dichroism (PCD) from achiral GNRs, it is necessary to partially replace the surface-coated cetyltrimethylammonium bromide with chiral molecules. Here, we present a supramolecular approach to generate and modulate the PCD of GNRs through the hybrid gelation of GNRs with an amphiphilic chiral dendron gelator. Upon gelation, the PCD could be produced and further regulated depending on the ratio of the dendrons to GNRs. It was revealed that the wrapping of the self-assembled nanofibers around the GNRs is crucial for generating the PCD. Furthermore, the hybrid gel underwent a thermotriggered gel-sol and sol-gel transformation, during which the PCD can disappear (solution) and reappear (gel), respectively, and such process can be repeated many times. In addition, the hybrid gel could also undergo shrinkage upon addition of a slight amount of Mg2+ ions, during which the PCD disappeared also. Thus, through the gel formation and subsequent metal ion- or temperature-triggered phase transition, PCD can be reversibly modulated. The results not only clarified the generation mechanism of PCD from the achiral GNRs without the chiral modification on the surface but also offered a simple and efficient way to modulate the PCD.

ChemInform Abstract: The First Organocatalytic Cope Rearrangement

AbstractReview: 11 refs.

The First Organocatalytic Cope Rearrangement.

Exploiting the concept of iminium ion catalysis led to the discovery of the first organocatalytic Cope rearrangement of 1,5-hexadiene-2-carboxaldehydes. A diazepane catalyst exhibited optimal catalytic efficiency and offers possibilities for chiral modification.

Experimental and theoretical investigation of the enantioselective hydrogenation of ethyl pyruvate with a Pt catalyst with new non-cinchona chiral modifiers

The enantioselective hydrogenation of ethyl pyruvate using a Pt/SiO2 catalyst modified with six different chiral modifiers was studied. The chiral modifiers chosen were: (S)-(+)-1-aminoindan, (R)-(−)-1-aminoindan, (1R,2S)-(+)-cis-1- amino-2-indanol, (1S,2R)-(−)-cis-1-amino-2-indanol, (S)-(+)-1-indanol and (R)-(−)-1-indanol.An excess of the (R) enantiomer of the product of 63% and 45% with (S)-(+)-1-aminoindan and (R)-(−)-1-aminoindan modifiers, respectively was obtained. When using (1S,2R)-(−)-cis-1-amino-2-indanol and (1R,2S)-(+)-cis-1-amino-2-indanol, the enantiomeric excess (ee%) obtained was 30% and 5%, respectively, while with both indanols ee% did not exceed 8%. Molecular modeling of the complex formed between the chiral modifier and ethyl pyruvate performed by DFT calculations allowed predicting the values of ee% obtained experimentally. The low ee% value obtained both aminoindanol chiral modifiers were used, could be explained by the analysis of non-covalent interactions (NCI) method. These calculations demonstrated the presence of an intramolecular hydrogen bond in the structure of these modifiers.

Adsorption and Performance of Chiral Cinchona Alkaloid Modifiers over Pd/C Catalyst for Enantioselective Hydrogenation of α-Phenylcinnamic Acids

Abstract The enantioselective hydrogenation reactions of α-phenylcinnamic acid (PCA) and 4,4′-dimethoxy α-phenylcinnamic acid (DMPCA) were carried out over chiral cinchona alkaloid-modified Pd/C. Two sets of the modifiers were employed to get deeper insights into the effects of relative adsorption strength between the modifier and the substrate on the enantioselectivity; cinchonidine (CD)/cinchonine (CN) and quinine (QN)/quinidine (QD). The performances of the two sets of modifiers were compared by systematically varying the modifier concentration over a wide range. It was clearly substantiated that the origin of the low selectivity observed with QN/QD at an ordinary concentration is primarily due to its weak adsorption strength on Pd metal surface, which originates from the steric hindrance of the methoxy substituent at C6. A new modifier, 6-hydroxy CD, was found to exhibit a performance comparable to that of CD, implying that the steric hindrance of the 6-methoxy group of QN/QD is much more influential than the electronic effects.

Toluene promotes lid 2 interfacial activation of cold active solvent tolerant lipase from Pseudomonas fluorescens strain AMS8

The utilization of cold active lipases in organic solvents proves an excellent approach for chiral synthesis and modification of fats and oil due to the inherent flexibility of lipases under low water conditions. In order to verify whether this lipase can function as a valuable synthetic catalyst, the mechanism concerning activation of the lid and interacting solvent residues in the presence of organic solvent must be well understood. A new alkaline cold-adapted lipase, AMS8, from Pseudomonas fluorescens was studied for its structural adaptation and flexibility prior to its exposure to non-polar, polar aprotic and protic solvents. Solvents such as ethanol, toluene, DMSO and 2-propanol showed to have good interactions with active sites. Asparagine (Asn) and tyrosine (Tyr) were key residues attracted to solvents because they could form hydrogen bonds. Unlike in other solvents, Phe-18, Tyr-236 and Tyr-318 were predicted to have aromatic-aromatic side-chain interactions with toluene. Non-polar solvent also was found to possess highest energy binding compared to polar solvents. Due to this circumstance, the interaction of toluene and AMS8 lipase was primarily based on hydrophobicity and molecular recognition. The molecular dynamic simulation showed that lid 2 (residues 148–167) was very flexible in toluene and Ca2+. As a result, lid 2 moves away from the catalytic areas, leaving an opening for better substrate accessibility which promotes protein activation. Only a single lid (lid 2) showed the movement following interactions with toluene, although AMS8 lipase displayed double lids. The secondary conformation of AMS8 lipase that was affected by toluene observed a reduction of helical strands and increased coil structure. Overall, this work shows that cold active lipase, AMS8 exhibits distinguish interfacial activation and stability in the presence of polar and non-polar solvents.

Three-Dimensional Carbon Allotropes Comprising Phenyl Rings and Acetylenic Chains in sp+sp(2) Hybrid Networks.

We here identify by ab initio calculations a new type of three-dimensional (3D) carbon allotropes that consist of phenyl rings connected by linear acetylenic chains in sp+sp2 bonding networks. These structures are constructed by inserting acetylenic or diacetylenic bonds into an all sp2-hybridized rhombohedral polybenzene lattice, and the resulting 3D phenylacetylene and phenyldiacetylene nets comprise a 12-atom and 18-atom rhombohedral primitive unit cells in the symmetry, which are characterized as the 3D chiral crystalline modification of 2D graphyne and graphdiyne, respectively. Simulated phonon spectra reveal that these structures are dynamically stable. Electronic band calculations indicate that phenylacetylene is metallic, while phenyldiacetylene is a semiconductor with an indirect band gap of 0.58 eV. The present results establish a new type of carbon phases and offer insights into their outstanding structural and electronic properties.

Discrimination of active species in liquid-phase hydrogenation on supported noble metal catalyst: An operando spectroscopic study on the asymmetric hydrogenation of ketopantolactone on Pt/Al2O3 and Pt/C modified by cinchonidine

An often encountered problem in in situ or operando spectroscopic studies on supported metal catalysts is the discrimination between adsorbates on the support and on the active metal. Here, we show that comparative studies involving differently supported catalysts can help discriminate between species adsorbed on the active metal and the support. The adsorption of the chiral modifier cinchonidine (CD) on Pt/Al2O3 and Pt/C catalysts was investigated by means of operando attenuated total reflection infrared (ATR-IR) spectroscopy. The choice of the support material was found to be crucial, as the strong signal contributions from adsorbates on alumina significantly hampered the spectroscopic analysis of the Pt/Al2O3 catalyst. Instead, the use of a corresponding carbon supported Pt catalyst facilitated the discrimination of adsorbates on the noble metal, due to the virtual absence of adsorbed modifier species on the carbon support. Under reaction conditions of the asymmetric hydrogenation of ketopantolactone, Pt nanoparticles were predominantly covered by CD species anchored via a tilted quinoline ring with respect to the metal surface. Our operando ATR-IR spectroscopic study indicates a strong correlation between the intensity of the signal associated to tilted CD species and the obtained enantioselectivity.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol.

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopic understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule's intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network's enantioselective interaction with other molecules.

A comparative study of diastereomeric complexes formed by a prochiral substrate and three structurally analogous chiral molecules on Pt(111)

A comparative study of chemisorbed bimolecular diastereomeric complexes formed by three structurally analogous chiral modifiers and a prochiral substrate on Pt(111) was performed using scanning tunneling microscopy (STM) and density functional theory (DFT) methods. The experiments determine, subject to a number of assumptions, the abundant binding configurations and whether the complexed substrate is organized into pro-S or pro-R states. The overall prochiral ratio (pr) estimated in this manner may be compared in each case to literature values for the enantiomeric ratio (er) observed in catalysis experiments. The experiments were performed using ketopantolactone as the substrate and (R)-1-(1-naphthyl)ethylamine, (R)-N-Methyl-1-(1-naphthyl)ethylamine and (R)-1-naphthyl-1,2-ethanediol as the structurally analogous chiral modifiers. The STM measurements were performed at room temperature to better mimic conditions under which the catalytic studies reported in the literature were performed. The results are discussed in terms of the stereochemical effects of subtle modifications of the structure of the chiral modifier.

ChemInform Abstract: Crucial Aspects in the Design of Chirally Modified Noble Metal Catalysts for Asymmetric Hydrogenation of Activated Ketones

AbstractReview: 50 refs.

Improvement of chiral stationary phases based on cinchona alkaloids bonded to crown ethers by chiral modification.

To improve the chiral recognition capability of a cinchona alkaloid crown ether chiral stationary phase, the crown ether moiety was modified by the chiral group of (1S, 2S)-2-aminocyclohexyl phenylcarbamate. Both quinine and quinidine-based stationary phases were evaluated by chiral acids, chiral primary amines and amino acids. The quinine/quinidine and crown ether provided ion-exchange sites and complex interaction site for carboxyl group and primary amine group in amino acids, respectively, which were necessary for the chiral discrimination of amino acid enantiomers. The introduction of the chiral group greatly improved the chiral recognition for chiral primary amines. The structure of crown ether moiety was proved to play a dominant role in the chiral recognitions for chiral primary amines and amino acids.