Enantioselective Ethylation of Various Aldehydes Catalyzed by Readily Accessible Chiral Diols

Four chiral C₂‐symmetric diols were synthesized in a straightforward three‐step reaction and demonstrated excellent enantioselectivities and good overall yields. Their catalytic activities were examined via the addition of diethylzinc to various aldehydes. The enantioselective addition of diethylzinc to 2‐methoxybenzaldehyde gave the corresponding chiral secondary alcohol with high yields (up to 95%) and moderate to good enantiomeric excess (up to 88%). All synthesized ligands were evaluated in the addition of diethylzinc to various aldehydes in the presence of an additional metal such as Ti(IV) complexes. Chirality 28:593–598, 2016. © 2016 Wiley Periodicals, Inc.     

Chirality Sensing With Stereodynamic Biphenolate Zinc Complexes

Two bidentate ligands consisting of a fluxional polyarylacetylene framework with terminal phenol groups were synthesized. Reaction with diethylzinc gives stereodynamic complexes that undergo distinct asymmetric transformation of the first kind upon binding of chiral amines and amino alcohols. The substrate‐to‐ligand chirality imprinting at the zinc coordination sphere results in characteristic circular dichroism signals that can be used for direct enantiomeric excess (ee) analysis. This chemosensing approach bears potential for high‐throughput ee screening with small sample amounts and reduced solvent waste compared to traditional high‐performance liquid chromatography methods. Chirality 27:700–707, 2015. © 2015 Wiley Periodicals, Inc.     

Absolute Configuration and Predominant Conformations of a Chiral Crown Ether‐Based Colorimetric Sensor: A Vibrational Circular Dichroism Spectroscopy and DFT Study of Chiral Recognition

In the present work, we report a comprehensive vibrational circular dichroism (VCD) spectroscopic study of a chiral crown ether which features an axial chiral 3.3'‐diphenyl‐1,1'‐binaphthyl group as chiral moiety. By comparing the experimental and calculated VCD spectra, we show that the presumably very flexible crown ether preferably adopts only one ring conformation. Conformational flexibility is observed in the 2,4‐dinitrophenyl‐diazophenol group, which was previously introduced for colorimetric detection of primary amines and amino alcohols (Cho et al., Chirality 2011;23:349–353). The VCD spectra of the host–guest complexes with phenyl glycinol (PG) and phenyl alaninol have been studied as well. Based on the spectra calculated, it is shown that the diastereomeric complexes in general can be differentiated using VCD spectroscopy. Furthermore, the experimental VCD spectra of the complexes of the host molecule with PG support the above finding. Chirality 25:294–300, 2013. © 2013 Wiley Periodicals, Inc.     

Enantioseparation of Four Organophosphonate Derivatives on N‐(3,5‐Dinitrobenzoyl)‐ l‐leucine–n‐Propylamide Stationary Phase by Molecular Modeling

Four groups of organophosphonate derivatives enantiomers were separated on N‐(3,5‐dinitrobenzoyl)‐S‐leucine chiral stationary phase. The three‐dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation. Detailed results regarding the conformation, auto‐docking, and thermodynamic estimation are presented. The elution order of the enantiomer could be determined from the energy. The predicted chiral discrimination was obtained by computational results. Chirality 25:101–106, 2013. © 2012 Wiley Periodicals, Inc.     

A Helical Polyphenylacetylene Having Amino Alcohol Moieties Without Chiral Side Groups as a Chiral Ligand for the Asymmetric Addition of Diethylzinc to Benzaldehyde

One‐handed helical polyphenylacetylenes having achiral amino alcohol moieties, but no chiral side groups, were synthesized by the helix‐sense‐selective copolymerization of an achiral phenylacetylene having an amino alcohol side group with a phenylacetylene having two hydroxyl groups. Since the resulting helical copolymers were successfully utilized as chiral ligands for the enantioselective alkylation of benzaldehyde with diethylzinc, we can conclude that the main‐chain chirality based on the one‐handed helical conformation is useful for the chiral catalysis of an asymmetric reaction for the first time. The enantioselectivities of the reaction were controlled by the optical purities of the helical polymer ligands. In addition, the polymer ligands could be easily recovered by precipitation after the reaction. Chirality 27:454–458, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis and Characterization of Conformationally Rigid Chiral Pyridine–N‐Heterocyclic Carbene‐Based Palladacycles with an Unexpected Pd–N Bond Cleavage

The versatility of a previously developed method for the synthesis of chiral carbene‐based palladacycles is demonstrated through the synthesis of two new chiral pyridine‐functionalized N‐heterocyclic carbene palladacycles with different wingtip groups. The efficiency in their resolution with different counter anions and different chiral amino acid salt auxiliaries has been studied. The absolute stereochemistries of all the chiral compounds were confirmed by single crystal X‐ray crystallography. An unexpected Pd–N bond cleavage that resulted in the racemization of the α‐carbon center in these complexes has also been investigated. Chirality 25:149–159, 2013. © 2013 Wiley Periodicals, Inc.     

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Chiral O,N,O‐tridentate Phenol Ligands Derived From Camphor

Chiral O,N,O‐tridentate phenol ligands bearing a camphor backbone were found to be effective chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in high enantioselectivities (80–95% ee) at room temperature. Chirality 28:65–71, 2016. © 2015 Wiley Periodicals, Inc.     

Chirality in Distorted Square Planar Pd(O,N)2 Compounds

Salicylidenimine palladium(II) complexes trans‐Pd(O,N)₂ adopt step and bowl arrangements. A stereochemical analysis subdivides 52 compounds into 41 step and 11 bowl types. Step complexes with chiral N‐substituents and all the bowl complexes induce chiral distortions in the square planar system, resulting in Δ/Λ configuration of the Pd(O,N)₂ unit. In complexes 1 , 2 , 3 , 4 , 5 , 6 with enantiomerically pure N‐substituents ligand chirality entails a specific square chirality and only one diastereomer assembles in the lattice. Dimeric Pd(O,N)₂ complexes with bridging N‐substituents in trans‐arrangement are inherently chiral. For dimers 7 , 8 , 9 , 10 , 11 different chirality patterns for the Pd(O,N)₂ square are observed. The crystals contain racemates of enantiomers. In complex 12 two independent molecules form a tight pair. The (R_C) configuration of the ligand induces the same Δ chirality in the Pd(O,N)₂ units of both molecules with varying square chirality due to the different crystallographic location of the independent molecules. In complexes 13 and 14 atrop isomerism induces specific configurations in the Pd(O,N)₂ bowl systems. The square chirality is largest for complex 15 [(Diop)Rh(PPh₃)Cl)], a catalyst for enantioselective hydrogenation. In the lattice of 15 two diastereomers with the same (R_C,R_C) configuration in the ligand Diop but opposite Δ and Λ square configurations co‐crystallize, a rare phenomenon in stereochemistry. Chirality 25:663–667, 2013. © 2013 Wiley Periodicals, Inc.     

Cheap and Long‐Life Reusable Polymer for Asymmetric Organozinc Catalysis Based on Camphor‐Derived Hydroxyamides

Polystyrene grafted with a chiral zinc‐complexing camphor‐derived N,N‐disubstituted hydroxyamide is proposed as a new type of functional polymer of high reusability for the development of sustainable organozinc‐catalyzed asymmetric reactions. The main goal of this new functional polymer is the ease of the hydroxyamide‐moiety preparation (cheap chiral ligand obtained straightforwardly from an enantiopure starting material coming from the chiral pool), as well as its chemical robustness when compared with other related zinc‐complexing functional groups. The latter allows the polymer to be active after multiple applications, without significant loss of its catalytic activity. This fact is exemplified by the design and preparation of a polymer functionalized with a bis(hydroxyamide) proved previously as active in the homogeneous enantioselective addition of diethylzinc to aldehydes. The result is a cheap functional polymer with a very high reusability (the enantioselectivity and chemical yield are maintained practically constant after 20 applications). Additionally, a methodology for the multicycle use of these functional polymers is presented. Chirality, 2012. © 2012 Wiley Periodicals, Inc.     

Comparative Enantioseparation of Ketoprofen with Trimethylated α‐, β‐, and γ‐Cyclodextrins in Capillary Electrophoresis and Study of Related Selector–Selectand Interactions Using Nuclear Magnetic Resonance Spectroscopy

The enantiomers of ketoprofen were separated by capillary electrophoresis using the (2,3,6‐tri‐O‐methyl)‐derivatives of α‐, β‐, and γ‐cyclodextrin (CyD) as chiral selectors. The affinity pattern of the ketoprofen enantiomers toward these CyDs changed depending on their cavity size. Thus, with hexakis (2,3,6‐tri‐O‐methyl)‐α‐CyD and heptakis (2,3,6‐tri‐O‐methyl)‐β‐CyD, the R enantiomer of the drug migrated first, whereas the enantiomer migration order was reversed in the presence of octakis(2,3,6‐tri‐O‐methyl)‐γ‐CyD. The change in the migration order was rationalized on the basis of changes in the structure of the complexes between the ketoprofen enantiomers and the chiral selectors as derived from nuclear magnetic resonance spectroscopy experiments. Chirality, 25:79–88, 2013.© 2012 Wiley Periodicals, Inc.     

Enantioselective complexation of 1‐phenylethanol with chiral compounds bearing urea moiety

A detailed study of diastereomeric complexes of chiral ureido‐1,1′‐binaphthalene derivatives with chiral 1‐phenylethanol showed that a derivative bearing only one urea unit makes five times more stable complex with (S)‐enantiomer than with (R)‐enantiomer of the alcohol. This phenomenon could be used in chiral discrimination processes. The influence of individual parts of the structure on the complexation properties is shown. The probable structure of diastereomeric complexes based on experimental results and computational methods is proposed.     

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di‐(benzyl)glycine Schiff bases. We found that while the ortho‐fluoro derivatives are configurationally unstable, the pure enantiomers of corresponding axially chiral ortho‐chloro‐containing complexes can be isolated by preparative HPLC and show exceptional configurational stability (t_1/2 from 4 to 216 centuries) at ambient conditions. Synthetic implications of this discovery for the development of new generation of axially chiral auxiliaries, useful for general asymmetric synthesis of α‐amino acids, are discussed.     

Planar Chiral Iridium Complexes with the Δ‐TRISPHAT Anion: Toward the First Enantiopure o‐Quinone Methide π‐Complex

We describe the resolution of a planar chiral cationic iridium complex [Cp*Ir(η⁵‐2‐methyl‐oxodienyl)][OT f] ( 2 ) following the counterion strategy, where anion metathesis by Δ‐TRISPHAT generates the two diastereomers (pR, pS)‐[Cp*Ir(η⁵‐2‐methyl‐oxodienyl)][Δ‐TRISPHAT] ( 3a , 3a' ). Upon fractional crystallization both compounds were separated as confirmed by ¹H nuclear magnetic resonance (NMR) and circular dichroism studies recorded in solution. The latter represents the key‐complex precursors for the enantioselective synthesis of metallated o‐quinone methide complexes ( 4a , 4a' ). Chirality 25:449–454, 2013. © 2013 Wiley Periodicals, Inc.     

Chiral Discrimination of Ammonium Neurotransmitters by C3‐Symmetric Enantiopure Hemicryptophane Hosts

Enantiopure hemicryptophanes efficiently discriminate chiral ammonium neurotransmitters. The ephedrine and norephedrine molecules associate with hemicryptophane hosts to form 1:1 and 1:2 host‐guest complexes. Binding constants are determined by fitting the ¹H nuclear magnetic resonance (NMR) titration curves to give β₁ and β₂ values, which are used to characterize the diastereomeric and enantiomeric discriminating potentials of the hosts. Chirality 25:47–479, 2013. © 2013 Wiley Periodicals, Inc.     

An Insight to Chiral Monolith for Enantioselective Nano and Micro HPLC: Preparation and Applications

This review gives an overview of chiral separation principles and their application in enantioselective nano/micro high performance liquid chromatography (n/μ‐HPLC) using chiral monolith. In particular, developments in silica and polymer chiral monolithic stationary phases are presented. The preparation and applications of chiral monoliths, the basic chiral separation principles and the mechanisms are discussed. Chirality 25:314–323, 2013. © 2013 Wiley Periodicals, Inc.     

Effect of Chromatographic Conditions on Enantioseparation of Bovine Serum Albumin Chiral Stationary Phase in HPLC and Thermodynamic Studies

Twelve chiral compounds were enantiomerically resolved on bovine serum albumin chiral stationary phase (BSA‐CSP) by high‐performance liquid chromatography (HPLC) in reversed‐phase modes. Chromatographic conditions such as mobile phase pH, the percentage of organic modifier, and concentration of analyte were optimized for separation of enantiomers. For N‐(2, 4‐dinitrophenyl)‐serine (DNP‐ser), the retention factors (k) greatly increase from 0.81 to 6.23 as the pH decreasing from 7.21 to 5.14, and the resolution factor (R_s) exhibited a similar increasing trend (from 0 to 1.34). More interestingly, the retention factors for N‐(2, 4‐dinitrophenyl)‐proline (DNP‐pro) decrease along with increasing 1‐propanol in mobile phase (3%, 5%, 7% and 9% by volume), whereas the resolution factor shows an upward trend (from 0.96 to 2.04). Moreover, chiral recognition mechanisms for chiral analytes were further investigated through thermodynamic methods. Chirality 25:487–492, 2013. © 2013 Wiley Periodicals, Inc.     

Enantioselective Degradation of the Chiral Fungicides Metalaxyl and Furalaxyl by Brevibacillus brevis

For almost four decades, the chiral fungicides metalaxyl and furalaxyl have been in use in plant protection on a global scale. Both substances are distributed as racemic mixtures, yet the desirable interference in nucleic acid synthesis of harmful fungi only occurs by the (‐)‐R‐enantiomer. As enantioselective degradation in Scheyern (Germany) and Yaoundé (Cameroon) soils has been documented, the influence of 50 isolated microorganisms on the R/S ratio was investigated. A high‐pressure liquid chromatography method with a chiral column to separate enantiomers of metalaxyl and furalaxyl, and subsequent detection by tandem mass spectrometry, was employed. Only one of these microorganisms, a strain of Brevibacillus brevis, showed an enantioselective degradation pattern in liquid culture; the respective (‐)‐R‐enantiomers were preferably degraded. Moreover, (‐)‐R‐furalaxyl was degraded faster in cultures supplemented simultaneously with both fungicides of the same concentration. Chirality 25:336–340, 2013. © 2013 Wiley‐Liss Inc. Chirality 00:000‐000:, 2013. © 2013 Wiley Periodicals, Inc.     

Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains

Flurbiprofen (F) is a nonsteroidal anti‐inflammatory drug (NSAID) used therapeutically as the racemate of (R)‐enantiomer and (S)‐enantiomer. The inversion of RF to SF and vice versa was investigated in C57Bl/6 and SJL mice and Dark Agouti and Lewis rats. The enzyme α‐methylacyl‐CoA racemase (AMACR) is involved in the chiral inversion pathway that converts members of the 2‐arylpropionic acid NSAIDs from the R‐enantiomer to the S‐enantiomer. We studied C57Bl/6 mice deficient in AMACR postulating that they should show reduced inversion of RF to SF. In line with the data of others in mice, (R)‐inversion to (S)‐inversion was relatively high in both the C57Bl/6 and SJL mice (fraction inverted, F_I = 37.7% and 24.7%, respectively). In contrast, in AMACR deficient mice, there was no measurable peak for SF after administration of RF. The results in both rat strains (Dark Agouti and Lewis rats, F_I = 1.4% and 4.1%, respectively) confirm the low chiral inversion of the enantiomers of flurbiprofen in the rat, as observed by other authors in the Sprague‐Dawley strain (<5%). From the present results, we conclude that for the study of flurbiprofen enantiomers, the rat is more suitable than the mouse as a model for the human in which (R)‐inversion to (S)‐inversion is negligible.     

DNA Binding,Antioxidant Activity,and DNA Damage Protection of Chiral Macrocyclic Mn(III) Salen Complexes

We are reporting the synthesis, characterization, and calf thymus DNA binding studies of novel chiral macrocyclic Mn(III) salen complexes S‐1 , R‐1 , S‐2 , and R‐2 . These chiral complexes showed ability to bind with DNA, where complex S‐1 exhibits the highest DNA binding constant 1.20 × 10⁶ M^?1. All the compounds were screened for superoxide and hydroxyl radical scavenging activities; among them, complex S‐1 exhibited significant activity with IC₅₀ 1.36 and 2.37 μM, respectively. Further, comet assay was used to evaluate the DNA damage protection in white blood cells against the reactive oxygen species wherein complex S‐1 was found effective in protecting the hydroxyl radicals mediated plasmid and white blood cells DNA damage. Chirality 24:1063–1073, 2012.© 2012 Wiley Periodicals, Inc.