Chiral Moiety Research Articles

Helix-Dependent Spin Filtering through the DNA Duplex.

Recent work suggests that electrons can travel through DNA and other chiral molecules in a spin-selective manner, but little is known about the origin of this spin selectivity. Here we describe experiments on magnetized DNA-modified electrodes to explore spin-selective electron transport through hydrated duplex DNA. Our results show that the two spins migrate through duplex DNA with a different yield and that spin selectivity requires charge transport through the DNA duplex. Significantly, shifting the same duplex DNA between right-handed B- and left-handed Z-forms leads to a diode-like switch in spin selectivity; which spin moves more efficiently through the duplex depends upon the DNA helicity. With DNA, the supramolecular organization of chiral moieties, rather than the chirality of the individual monomers, determines the selectivity in spin, and thus a conformational change can switch the spin selectivity.

First P,P*-bidentate ligands with P*-chiral diamidophosphite and arylphosphine moieties in Pd-catalyzed asymmetric reactions

GRAPHICAL ABSTRACT

Constructing Crystalline Covalent Organic Frameworks from Chiral Building Blocks.

Covalent organic frameworks (COFs) represent a new type of crystalline porous materials that are covalently assembled from organic building blocks. Construction of functional COFs is, however, a difficult task because it has to meet simultaneously the requirements for crystallinity and functionality. We report herein a facile strategy for the direct construction of chiral-functionalized COFs from chiral building blocks. The key design is to use the rigid scaffold 4,4'-(1H-benzo[d]imidazole-4,7-diyl)dianiline (2) for attaching a variety of chiral moieties. As a first example, the chiral pyrrolidine-embedded building block (S)-4,4'-(2-(pyrrolidin-2-yl)-1H-benzo[d]imidazole-4,7-diyl)dianiline (3) was accordingly synthesized and applied for the successful construction of two chiral COFs, LZU-72 and LZU-76. Our experimental results further showed that these chiral COFs are structurally robust and highly active as heterogeneous organocatalysts.

Hydrogen Bonding Networks in Chiral Thiourea Organocatalysts: Evidence on the Importance of the Aminoindanol Moiety

The crystal structures of four chiral thioureas, which are normally used as organocatalysts, are reported by the first time. Each compound is assembled in the crystal in a different way according to their chiral moiety in the thiourea skeleton, being dependent on the presence or the absence of the OH group in the aminoindanol or aminoindane moiety, respectively. Thiourea 1, which contains an aminoindane group, is assembled into a zigzag chain linked via N–H···S hydrogen bonds. Thiourea 2, with an aminoindanol and a phenyl group, interacts mainly through O–H···S and N–H···S bonds in a very congested structure. Thiourea 3 disposes in a zigzag chain mainly through S···O–H bonds and in further superposed zigzag chains through N–H···S hydrogen bonds. The compound 4 is coordinated in a coplanar organization via O···H–N interactions, forming very tight dimers, which are further arranged in chain of dimers through O–H···S interactions. The general trends in the patterns of packing of these four compounds are comp...

Bifunctional Thioureas with α-Trifluoromethyl or Methyl Groups: Comparison of Catalytic Performance in Michael Additions.

Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group. Their catalytic performance in representative Michael addition reactions was used in an effort to compare the electronic effects of the fluorination at the methyl group. The observed differences concerning yields and ee values cannot be attributed solely to the different steric environments; theoretical results indicate distinct interactions within the corresponding transition states. The calculated transition states show that the fluorinated catalysts have stronger N-H···O and C-H···F hydrogen bonds, while the nonfluorinated systems have C-H···π contacts. These results have shown that a variety of hydrogen-bonding interactions are important in determining the yield and selectivity of thiourea organocatalysis. These details can be further exploited in catalyst design.

A Chiral Hemiporphyrazine Derivative: Synthesis and Chiroptical Properties.

The synthesis of an optically active hemiporphyrazine with chiral binaphthyl substituents (1) is reported, providing the first example of the incorporation of an intrinsically chiral moiety into the macrocyclic core of a hemiporphyrazine analogue. A negative circular dichroism (CD) signal is observed in the 325-450 nm region of the CD spectrum of (S,S)-1, while mainly positive bands are observed in the 220-325 nm region. Mirror symmetry is observed across the entire wavelength range of the CD spectra of (R,R)-1 and (S,S)-1. An irreversible one-electron oxidation wave with an onset potential at 1.07 V is observed by cyclic voltammetry, along with a reversible one-electron reduction wave at -0.85 V. Density functional calculations reproduce the experimentally observed data and trends, and provide further insight into the nature of the electronic transitions.

(Invited) 'totem' C2-Symmetrical Iron(III) Porphyrin Complexes to Stereoselectively Promote the Alkene Cyclopropanation

The stereoselective synthesis of cyclopropanes is an important issue in synthetic chemistry due to the relevance of these three-member carbon rings which often represent the active part in biological and/or pharmaceutical compounds.1,2 The one pot reaction of diazo compounds with alkenes represents a sustainable methodology to achieve cyclopropanes due to the formation of N2 as the only stoichiometric by-product. The reaction is efficiently catalysed by metal porphyrins which promote the synthesis of cyclopropanes with excellent diastereo- and enantioselectivities. Considering the importance in developing eco-friendly catalytic procedures, we are currently studying the catalytic activity of iron porphyrins which display a cheap, efficient and low toxic metal centre.The two iron complexes 1Fe and 2Fe are good catalysts for the alkene cyclopropanation and both have one C2 axis within the porphyrin plane and exhibit an open space on each side for the substrate access. Complex 1Fe displays a pre-organized structure which was responsible for excellent trans-diastereoselectivities (94-99%) in alkene cyclopropanations while the presence of chiral moieties in 2Fe allowed to perform the reactions with also a very good enantioselectivity (up to 87%).2 Experimental data disclosed that each ‘totem’ portion of 2Fe has a specific catalytic role: i) the porphyrin core containing the active iron centre is in charge to activate the diazo compound; ii) benzylic moieties are responsible for the reaction diasteroselectivity and iii) the two chiral binaphthyl groups allow the enantioselective synthesis of cyclopropanes. The study of the reaction scope revealed that both 1Fe and 2Fe catalysts were active in promoting the cyclopropanation of several olefins by differently substituted diazo compounds.

Synthesis and Application of C2 and C3 Symmetric (R)-Phenylglycinol-Derived Chiral Stationary Phases.

A C3 symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral stationary phase (CSP) and three C2 symmetric (R)-phenylglycinol CSPs were newly synthesized using o-, m-, and p-phthaloyl dichlorides. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5-dinitrobenzoyl (R)-phenylglycinol-derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution.

Biocatalytic reduction of racemic 2-arenoxycycloalkanones by yeasts P. glucozyma and C. glabrata: one way of achieving chiral 2-arenoxycycloalcohols.

Chiral β-aryloxy alcohols are interesting building blocks that form part of drugs like β adrenergic antagonists. Acquiring cyclic rigid analogs to obtain more selective drugs is interesting. Thus, we used whole cells of yeast strains Pichia glucozyma and Candida glabrata to catalyze the reduction of several 2-arenoxycycloalkanones to produce chiral 2-arenoxycycloalcohols with good/excellent enantioselectivity. In both cases, the alcohol configuration that resulted from the carbonyl group reduction was S. Yeast P. glucozyma allowed the conversion of both enantiomers of the starting material to produce 2-arenoxycycloalcohols with configuration (1S, 2R) and (1S, 2S). The reaction with C. glabrata nearly always allowed the kinetic resolution of the starting ketone, recovering 2-arenoxycycloalkanone with configuration S and (1S, 2R)-2-arenoxycycloalcohol.All the four possible stereoisomers of 2-phenoxycyclohexanol and the two enantiomers of 2-phenoxycyclohexanone were obtained by combining the biocatalyzed reaction with the oxidation/reduction of the chiral compounds with standard reagents. This is a simple approach for the synthesis of the rigid chiral moiety 2-arenoxycycloalcohols contained in putative β-blockers 2-arenoxycycloalkanepropanolamines.

A New Set of Isoreticular, Homochiral Metal–Organic Frameworks with ucp Topology

A new isoreticular series of metal–organic frameworks, called UHM-25 (UHM: University of Hamburg Materials), based on the copper paddle wheel motif and a novel set of homochiral linkers has been synthesized. Starting from amino acids available from the chiral pool a synthesis procedure was established that allows a straightforward, multigram scale synthesis of homochiral linkers in 4–5 steps. These linkers carry substituents that have been proven useful in stereoselective organic chemistry, such as the Evans auxiliary or chiral amino alcohols. The resulting MOFs only differ in the chiral moiety provided by the amino acid starting material. The structure of UHM-25 is composed of cuboctahedral cages of Cu2 paddle wheel motifs connected by the isophthalate moieties of the linker. These cages are linked via the bent backbone of the linker resulting in a primitive cubic arrangement, giving rise to the rare underlying (3,4)-c binodal net ucp. MOFs of the UHM-25 series show surface areas up to SBET = 1900 m2/g. ...

Synthesis and characterization of chiral PEDOT enantiomers bearing chiral moieties in side chains: chiral recognition and its mechanism using electrochemical sensing technology

This manuscript reports a couple of novel polymers of side-chain functionalized PEDOT. The new polymers can be employed to successfully recognize 3,4-dihydroxyphenylalanine enantiomers and we also discuss the mechanism of chiral recognition.

Recent Advances in Sensing Using Atropoisomeric Molecular Receptors.

We describe recent advances in chiroptical chemical sensors, in which the design and implementation is based upon the introduction of atropoisomerically chiral moiety within the molecular skeleton. This report include examples of acyclic, macrocyclic, and polymeric receptors that contain this motif. Although the main applications are in the enantioselective sensing of analytes, we report here some cases where the chiral receptors can in fact be used to senseachiral species. Using circular dichroism (CD) spectroscopy as the technique to detect a receptor-analyte interaction, we can distinguish two main sensor categories: that in which the CD signal of a stereolabile, CD-silent probe is activated upon binding, and that in which the signal of a CD-active probe is modulated upon binding. Particular emphasis will be given to cases in which CD spectroscopy is used orthogonally to other means of detection.

ChemInform Abstract: Pinene‐Derived Monodentate Phosphoramidites for Asymmetric Hydrogenation.

AbstractNewly synthesized phosphoramidite ligands are used in asymmetric catalysis.

Photo- or Electrically-induced Molecular Organizations Observed in Dichiral Azobenzene Liquid-crystalline Compounds

Azobenzene liquid crystals, possessing two chiral moieties at both of the peripheral ends of the molecular structure, show characteristic chirality-originated liquid-crystalline and physical properties: emergence of stable smectic Q phases, a photoinduced phase transition between 3D liquid crystal phases, and induction of birefringence in the “liquid” phase. A dichiral compound, of which rigidity of the core is reduced by the introduction of ester groups, showed no smectic Q phases, but exhibited the antiferroelectric smectic C phase. The “liquid” phase of the less-rigid azo-compound was found to show electrically induced birefringence.

Synthesis of new N-substituted chiral phosphine–phosphoramidite ligands and their application in asymmetric hydrogenations and allylic alkylations

Phosphine–phosphoramidite ligands containing a 2,4-pentanediyl backbone, BINOL moieties, and Me, Bn or Ph substituent on the nitrogen were synthesized and fully characterized. The electronic effect of the N-substituents was examined by 31P NMR of their corresponding seleno-phosphate-amide and phosphine–selenide derivatives. The new ligands together with their earlier reported derivatives were tested in the palladium catalyzed asymmetric allylic alkylation of rac-(E)-1,3-diphenylallyl acetate. Remarkably high activity (up to 1780h−1 turnover frequency) and first order kinetics were observed by facilitating nucleophile formation. The substituent at the nitrogen and the configuration of chiral moieties had a high impact on the enantioselectivity. The new ligands were also tested in the rhodium-catalyzed asymmetric hydrogenation of methyl (Z)-α-acetamidocinnammate, dimethyl itaconate (up to 99.9% ee’s) and methyl 2-acetamidoacrylate (up to 99.5% ee).

Helical self-assembly and nonlinear optical properties of two optically active phthalocyanine derivatives with the same chiral substituents on the α or β position

An optically active phthalocyanine derivative with eight (S)-2-methylbutoxy moieties linked on α-position is originally synthesized. Through electronic absorption, circular dichroism (CD), fluorescence spectra, scanning electron microscopy (SEM) and X-ray diffraction (XRD) technique, its helical self-assembly and nonlinear optical properties are comparatively investigated with its analogous which has the same chiral moieties linked on β-position substitutions. Although these two complexes possess the same chiral functional group, they exhibit different CD signals in the Q absorption region of corresponding complex and self-assemble into different morphologies. One self-assembles into right-handed ribbon-like aggregates while the other one is left-handed fibers. In addition, both complexes show good third-order nonlinear optical property.

Microwave-Assisted Synthesis of Bidentate Chiral Unsymmetrical Urea Derivatives of P-tert-butylcalix[4]Arene and their Anion Recognition Properties

Four new derivatives of p-t-butylcalix[4]arene containing two (1,3-distal) chiral unsymmetrical urea moieties at the lower rim were synthesised in four steps. Their anion recognition properties toward MeCO2−, H2PO4−, NO3−, I−, Br−, Cl− were assessed by UV-Vis titration spectroscopy. All the receptors showed the strongest recognition ability for MeCO2−, one of them having an association constant of 3139 M-1. 1H NMR studies of this receptor complex confirmed its tight binding of MeCO2−.

A Rapid, Robust and Ultra-Sensitive HPLC Enantioseparation of β-Amino Alcohols.

Enantioseparation of amino acid analogues racemic β-amino alcohols has hitherto been thought impossible without prior derivatization. Method developers of chromatographic enantioseparation often face detection challenge due to low ultraviolet (UV) absorbance of these molecules. A new chiral derivatizing reagent, benzimidazole-(S)-naproxen amide, was synthesized to provide UV detectable chiral moiety for detection of respective diastereomers of eight β-amino alcohols (dl-alaninol, dl-leucinol, dl-prolinol, dl-phenylalaninol, dl-phenylglycinol, dl-valinol, dl-homophenylalaninol and dl-methioninol). An HPLC method has been developed and validated and both the diastereomers were separated within 31 min runtime. Excellent resolution to a pmol detection limit level was achieved. The developed HPLC method for enantioseparation of β-amino alcohols is the first-ever report of its own kind having such a high detection sensitivity.

Chiral recognition of abacavir enantiomers by (2-hydroxy)propyl-β-cyclodextrin: UHPLC, NMR and DFT studies

The diastereomeric complexation of both abacavir (ABA) and its enantiomer (ABAE) with (2-hydroxy)propyl-β-cyclodextrin (2HPβCD) with a degree of substitution of seven was studied. The apparent binding constants of diasteromeric complexes, ABA-2HPβCD and ABAE-2HPβCD were determined by ultra high-pressure liquid chromatography (UHPLC) and found to be 517.0 and 684.4 M−1 respectively. The stoichiometry of the complexes was determined by UHPLC and by the continuous variation method using nuclear magnetic resonance spectroscopy giving 1:1 complexes. The apparent binding constants decrease as the temperatures increases. The observed enantio-differentiation was analyzed theoretically by density functional theory at the PBE/6-31 g** level using a polarizable continuous model (PCM) for solvent effects, the most stable complexes are the ones in which the chiral cyclopentenyl moiety is included in the cavity of CD and the protonated purine ring interact with the hydroxypropyl groups of 2HPβCD. The differences in stability of diasteromeric complexes, due to different intermolecular interactions are consistent with experimental data, providing further insights in the formation of inclusion complexes.

Biphenyl Based Non-symmetrical Bent-Core Mesogens Containing a Chiral Moiety and an Olefinic End Group

New nonsymmetrical bent-core compounds consisting of a biphenyl-3,4′-diol central unit, a chiral terminal chain and an olefinic end group at the other terminus have been synthesized and characterized to study the influence of a chiral moiety, the length of terminal alkenyl chain, and the number of aromatic rings in the rod-like wings which are substituted at the 3- and 4-position of central biphenyl core on mesophase properties of bent-core mesogens. The liquid crystalline properties of the compounds were investigated by differential scanning calorimetry, optical polarizing microscopy, and electro-optic methods. Depending on the length of the olefinic chain and the number of aromatic rings in the rod-like wings, the bent-core compounds with a chiral moiety show B1 type mesophase, polar smectic C phase (SmCP) or nonmesomorphic behavior.