Chiral Mono Research Articles

Chiral mono- and dinuclear CoII and CuII enantiomeric pairs with distinct enantiopure N-donor ligands: Presenting highly enhanced third-harmonic generation responses

Employing Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2 to react with enantiopure bidentate (1LR/1LS) and bis-bidentate (2LR/2LS) N-donor ligands, respectively, four chiral mono- and dinuclear CoII and CuII enantiomeric pairs formulated as M(hfac)2(1LR)/M(hfac)2 (1LS) (M = CoII, R-1-Co/S-1-Co and CuII, R-1-Cu/S-1-Cu) and M2(hfac)4(2LR)/M2 (hfac)4(2LS) (M = CoII, R-2-Co/S-2-Co and CuII, R-2-Cu/S-2-Cu) were isolated, where 1LR/1LS = (−)/(+)-4,5-pinene-2,2ʹ-bipyridine, 2LR/2LS = (−)/(+)-2,5-bis(4ʹ,5ʹ-pinene-2ʹ-pyridyl)pyrazine and hfac− = hexafluoroacetylacetonate. A study of their nonlinear optical responses reveals that dinuclear CoII and CuII enantiomers based on the symmetric 2LR/2LS ligands with larger π-conjugated systems only display very strong THG (third-harmonic generation) responses, while mononuclear ones based on the asymmetric 1LR/1LS ligands with smaller π-conjugated systems simultaneously present THG and SHG (second-harmonic generation) responses. More remarkably, THG intensities of dinuclear R-2-Co and R-2-Cu are 406 and 372 × α-SiO2, being 6.5 and 8.1 times those of the corresponding mononuclear R-1-Co and R-1-Cu, respectively. Furthermore, THG intensities of R-1-Co and R-1-Cu are 6.4 and 5.9 times those of their corresponding precursors Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2, respectively. The results indicate continuous large enhancements of the THG intensities from the precursors Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2 to their mononuclear enantiomers and further to their dinuclear species as the conjugation degrees of their ligands increase.

Supramolecular Catalysis with Chiral Mono- and Bis-(Thio)Urea-Derivatives

Chiral mono- and bis-(thio)urea supramolecular organocatalysts were studied in the enantioselective vinylogous addition reaction of 2-trimethylsilyloxyfuran (TMSOF) to carbonylic compounds; the corresponding chiral γ-hydroxymethyl-butenolides are obtained in good yields and with high enantiomeric excesses. The catalyst structure, as well as the reaction conditions, strongly influence the efficiency of the reaction. The conformational features of mono(thio)urea catalysts 2 and 3 and bis(thio)urea catalysts 7 and 8 were investigated by DFT calculations along with the structure of their complexes with benzaldehyde. Natural Bond Orbital (NBO) and Non-Covalent Interaction (NCI) calculations provided useful information concerning the activating H-bonding interactions in the complexes.

Chiroptical Recognition of Carboxylates with Charge-Neutral Double-Stranded Zinc(II) Helicates.

Chirality analysis of small molecules for the determination of their enantiopurity is nowadays ruled by streamlined chromatographic methods which utilize chiral stationary phases. Chiroptical probes which rely on host-guest interactions are so far overshadowed by the latter but have the benefit of depending only on common spectroscopic techniques such as CD spectroscopy to distinguish enantiomers and to quantify their ratio. Interest into this receptor-based approach is constantly rising because non-invasive high-throughput screenings with a minimal waste production can be performed. In this study we investigate the possibility to utilize metal-based containers in form of charge-neutral helicates able to recognize anions for this purpose. Key building block of the helicates are triazole units which show rotational freedom and give rise to either a meso-structure or a racemic mixture of the right- and left-handed complex. A chiroptical response of the probe is observed upon recognition of chiral mono- or dicarboxylates and chirality analysis of tartrate is conducted by CD spectroscopy.

Nitrene‐Mediated C−H Oxygenation: Catalytic Enantioselective Formation of Five‐Membered Cyclic Organic Carbonates

The synthesis of non-racemic 5-membered cyclic carbonates from abundant alcohols is reported. Conversion of the alcohol into an azanyl carbonate is followed by a chiral-at-ruthenium catalyzed cyclization to provide chiral cyclic carbonates in yields of up to 95% and with up to 99% ee. This new synthetic method is proposed to proceed through a nitrene-mediated intramolecular C(sp 3 )−H oxygenation which includes a very unusual 1,7-hydrogen atom transfer within a ruthenium nitrenoid intermediate. The method is applicable to the synthesis of non-racemic chiral mono-, di- and trisubstituted cyclic alkylene carbonates.

Atroposelective Synthesis of C-C Axially Chiral Compounds via Mono- and Dinuclear Vanadium Catalysis.

Axially chiral compounds with rotationally constrained σ-bonds that exhibit atropisomerism are lucrative synthetic targets because of their ubiquity in functional materials and natural products. The metal complex-catalyzed enantioselective fabrication of axially chiral scaffolds has been widely investigated, and thus far, considerable progress has been made. Over the past two decades, we have developed a highly efficient strategy for constructing axially chiral biarenol derivatives using chiral mono- and dinuclear vanadium complexes. These complexes are readily prepared from vanadium(IV) salts and Schiff base ligands (generated from the condensation of (S)-tert-leucine and di- or monoformyl-(R)-1,1'-bi-2-naphthol (BINOL) derivatives) under O2 and act as highly active catalysts for highly stereoselective C-C bond formation. In particular, the vanadium complex-catalyzed enantioselective oxidative coupling of 2-naphthols 1 under oxygen or in air, which is a green oxidant, affords the desired axially chiral molecules in high yields and high stereoselectivity (up to quantitative yield and 97% ee), along with water as the sole coproduct. This coupling reaction tolerated various functional groups (such as halogens, alkoxys, and boryls) and avoided overoxidation of coupling products.The key feature of dinuclear vanadium(V) catalysts such as (Ra,S,S)-5a is an outstanding mode of the homocoupling reaction, in which a single molecule of the catalyst activates two molecules of the starting material (e.g., 2-naphthols) simultaneously. With this "dual activation" mechanism, the oxidative coupling promoted by the dinuclear catalyst proceeds in an intramolecular manner. The homocoupling rate using 5 mol % of the dinuclear vanadium(V) complex (Ra,S,S)-5a was measured to be 111 times faster than that of the mononuclear vanadium(IV) complex (S)-4a bearing a half motif of the dinuclear vanadium complex.In the case of the heterocoupling reaction utilizing two different kinds of arenol derivatives, only a starting arenol having lower oxidation potential seems to be activated by the mononuclear vanadium complex. The reaction rate of the heterocoupling using either mono- or dinuclear vanadium complexes showed no difference to give the coupling product in high yields but with a different enantioselective manner; chiral mononuclear vanadium(V) complexes showed better enantioselectivites than that of the dinuclear vanadium(V) complexes. A competing heterocoupling study and a linear correlation between the ee of the mononucaler vanadium catalyst and ee of the heterocoupling suggested that the heterocoupling involves an intermolecular radical-anion coupling pathway.In this Account, we summarize the recent advances in vanadium-catalyzed coupling reactions that produced important chiral molecules, such as biresorcinols, polycyclic biphenols, oxa[9]helicenes, bihydroxycarbazoles, and C1-symmetrical biarenols, and their coupling reaction mechanisms. By pursuing vanadium catalysis, we believe numerous additional transformations as well as a renewed interest in catalytic and chemo-, regio-, and enantioselective aryl-aryl bond constructions will be manifested.

Design, efficient synthesis, structural characterization and coordination chemistry of chiral ferrocenyl hydrazone ligands

In recent year, the chemistry of ferrocene and the design of new compounds containing the ferrocene unit, has received a surge in interest, owing to their utility in many fields such as organic synthesis, catalysis and biotechnology material. The design and synthesis of new families of chiral ligands constitutes the starting task for many particular pieces of research that have contributed to the spectacular growth of asymmetric catalysis. Currently, there is a growing interest in nitrogen-based ligands, which offer a much higher structural variability and are easier to handle and recycle. During the last few years, we accumulated some knowledge about the synthesis, reactivity and structural aspects of the chemistry of N,N-dialkylhydrazones. These compounds, viewed as N-dialkylamino imine, exhibit a higher thermal stability as a result of the n → π conjugation. The behavior of the C = N bond is strongly dependent on the structure of the amine moiety, which in turn control the efficiency of the conjugation and may incorporate structural elements able to modulate the steric crowding around the coordination site, which make these compounds an interesting class of potentially useful ligands, in addition a literature survey revealed very few examples of the use of chiral mono or bis hydrazones as ligands in asymmetric catalysis. An efficient and easy access to a new classe family of ferrocenyl thiophosphine hydrazones ligands, using a carbaldehyde ferrocene functionalized in 1,2 position as starting material is reported, the obtained ligands were fully characterized by NMR 1H, 13C, 31P and HRMS ESI + spectroscopy and their coordination chemistry with some transition metal of interest such as PdII was studied, examples of the synthesis and structural characterization of some obtained complexes and application will be also given.

Recognition and Sensing of Chiral Organic Molecules by Chiral Porphyrinoids: A Review

Porphyrinoids are extremely attractive for their electronic, optical, and coordination properties as well as for their versatile substitution at meso/β-positions. All these features allow porphyrinoids to behave as chiroptical hosts for chiral recognition by means of non-covalent interactions towards chiral guests. Over the years, chiral discrimination of chiral molecules such as amino acids, alcohols, amines, hydroxy-carboxylic acids, etc. has aroused the interest of the scientific community. Hence, this review aims to report on the progress to date by illustrating some relevant research regarding the chiral recognition of a multitude of chiral organic guests through several chiral mono- and bis-porphyrins via different spectroscopic techniques.

Enantiodifferentiating Photodimerization of a 2,6-Disubstituted Anthracene Assisted by Supramolecular Double-Helix Formation with Chiral Amines.

A novel 2,6-anthrylene-linked bis(m-terphenylcarboxylic acid) strand (1) self-associates into a racemic double-helix. In the presence of chiral mono- and diamines, either a right- or left-handed double-helix was predominantly induced by chiral amines sandwiched between the carboxylic acid strands with accompanying stacking of the two prochiral anthracene linker units in an enantiotopic face-selective way, as revealed by circular dichroism and NMR spectral analyses. The photoirradiation of the optically active double helices complexed with chiral amines proceeded in a diastereo- (anti or syn) and enantiodifferentiating way to afford the chiral anti-photodimer with up to 98 % enantiomeric excess when (R)-phenylethylamine was used as a chiral double-helix inducer. The resulting optically active anti-photodimer can recognize the chirality of amines and diastereoselectively complex with chiral amines.

Enantiodifferentiating Photodimerization of a 2,6‐Disubstituted Anthracene Assisted by Supramolecular Double‐Helix Formation with Chiral Amines

AbstractA novel 2,6‐anthrylene‐linked bis(m‐terphenylcarboxylic acid) strand (1) self‐associates into a racemic double‐helix. In the presence of chiral mono‐ and diamines, either a right‐ or left‐handed double‐helix was predominantly induced by chiral amines sandwiched between the carboxylic acid strands with accompanying stacking of the two prochiral anthracene linker units in an enantiotopic face‐selective way, as revealed by circular dichroism and NMR spectral analyses. The photoirradiation of the optically active double helices complexed with chiral amines proceeded in a diastereo‐ (anti or syn) and enantiodifferentiating way to afford the chiral anti‐photodimer with up to 98 % enantiomeric excess when (R)‐phenylethylamine was used as a chiral double‐helix inducer. The resulting optically active anti‐photodimer can recognize the chirality of amines and diastereoselectively complex with chiral amines.

Chiral mono- and dicarbamates derived from ethyl (S)-lactate: convenient chiral solvating agents for the direct and efficient enantiodiscrimination of amino acid derivatives by 1H NMR spectroscopy.

New chiral solvating agents (CSAs) for NMR spectroscopy have been obtained from ethyl (S)-lactate, a very cheap commercially available product. By a sequence of simple chemical modifications of its functional groups, monocarbamoylated and dicarbamoylated derivatives were obtained, the potentialities of which as CSAs for NMR spectroscopy have been explored. Their ability to differentiate the resonances of enantiomeric mixtures of amino acids bearing a 3,5-dinitrobenzoyl moiety at the amino group and with the carboxyl function derivatized as methyl ester or amide has been probed. Almost every CSA was able to originate enantiodiscrimination in the 1H NMR spectra, with (2S)-1-(3,5-dimethylphenylcarbamoyloxy)-2-(3,5-dinitrophenylcarbamoyloxy)propane (4) standing out for efficiency and versatility.

Synthesis of Solid-phase Supported Chiral Amines and Investigation of Stereoselectivity of Aldol Reactions of Amine-free Tropinone Enolate

Seven selected chiral mono-, di-, and tridentate amines supported on insoluble polymer were effectively prepared from corresponding primary amines or secondary amino alcohols and Merrifield resin. The reaction of the polymer-supported amines with excess n-butyllithium gave the corresponding lithium amide bases, which were tested in the aldol reactions of tropinone with benzaldehyde. The deprotonation reactions were carried out with or without separation of the lithium enolate from polymer-supported reagents. Using the procedure with separation of lithium enolate from supported chiral reagent different results were obtained with or without the addition of LiCl despite the fact that aggregate formation of Merrifield resin supported Li-amides is hindered. Without the additive, the aldol products were obtained in low diastereoselectivity and enantioselectivity, whereas the addition of LiCl resulted in a significant increase of de and ee even when LiCl was added after the deprotonation step and separation of the chiral amine.

Catalytic Asymmetric C-H Arylation of (η6-Arene)Chromium Complexes: Facile Access to Planar-Chiral Phosphines.

A catalytic asymmetric direct C–H arylation of (η6-arene)chromium complexes to obtain planar-chiral compounds is reported. The use of the hemilabile ligand H8-BINAP(O) is key to providing high enantioselectivity in this transformation. We show that this methodology opens the door to the synthesis of a variety of planar-chiral chromium derivatives which can be easily transformed into planar chiral mono- or diphosphines. Mechanistic studies, including synthesis and characterization of Pd and Ag complexes and their detection in the reaction mixture, suggest a Pd-catalyzed/Ag-promoted catalytic system where Ag carries out the C–H activation step.

Synthesis of new chiral mono- and diacrylates for ferro- and antiferroelectric liquid crystals

The synthesis and characterization of new, chiral and reactive single liquid crystals based on biphenyl benzoate core are described. Compounds are terminated with partially perfluorinated alkoxy chain (monoacrylates) or acryloyloxy-alkoxy chain (diacrylates) on the non-chiral side of molecule, while the opposite terminal side is chiral acryloyloxy unit. New families of smectic LCs present alternative molecular approach to the monomer design. Compounds are characterized by mass spectrometry (electron ionization) analysis, proton and carbon nuclear magnetic resonance. They show liquid crystal behavior in broad temperature ranges, confirmed by a polarizing thermomicroscopy and differential scanning calorimetry. Detailed synthetic procedures are attached. Synthesized compounds stand as promising candidates for polymer stabilization of chiral liquid crystalline materials.

Chiral Mono(borohydride) Complexes of Scandium and Lutetium and Their Catalytic Activity in Ring-Opening Polymerization of dl-Lactide

The enantiopure mono(borohydride) rare-earth complexes [Ln{(S)-PETA)}2(BH4)] (Ln = Sc (1), Lu (2); PETA = N,N′-bis((S)-1-phenylethyl)-tert-butylamidinate) are reported. The synthesis was achieved by salt metathesis reactions of the homoleoptic tris(borohydrides) [Ln(BH4)3(thf)n] and (S)-LiPETA. Complexes 1 and 2 were fully characterized, including single-crystal X-ray diffraction. Compounds 1 and 2 were evaluated as initiators for the ring-opening polymerization (ROP) of racemic lactide. Both 1 and 2 were found to be active in the ROP of dl-lactide. Polymerizations carried out in toluene show a higher activity for 2 but a lower selectivity in comparison to the scandium derivative.

Enantiopurity and absolute configuration determination of arene cis-dihydrodiol metabolites and derivatives using chiral boronic acids.

The relative merits of the methods employed to determine enantiomeric excess (ee) values and absolute configurations of chiral arene and alkene cis-1,2-diol metabolites, including boronate formation, using racemic or enantiopure (+) and (-)-2-(1-methoxyethyl)phenylboronic acid (MEPBA), are discussed. Further applications of: 1) MEPBA derived boronates of chiral mono- and poly-cyclic arene cis-dihydrodiol, cyclohex-2-en-1-one cis-diol, heteroarene cis/trans-2,3-diol, and catechol metabolites in estimating their ee values, and 2) new chiral phenylboronic acids, 2-[1-methoxy-2,2-dimethylpropyl]phenyl boronic acid (MDPBA) and 2-[1-methoxy-1-phenylmethyl]phenyl boronic acid (MPPBA) and their advantages over MEPBA, as reagents for stereochemical analysis of arene and alkene cis-diol metabolites, are presented.

Study of aryl triazoles for absolute configuration determination

A variety of chiral mono- and di-1,4-disubstituted 1,2,3-triazoles were synthesized by CuAAC ‘click chemistry’ as model compounds and their spectroscopic properties characterized. The UV and CD studies of these compounds showed that 4-substituted aryl triazoles give rise to moderate exciton CD curves, under either homo- or hetero-coupling. The direction of the electric transition moment of the non-symmetric chromophores was determined by conformational analysis and supported by NMR data. The signs of the Cotton effects of the CD spectra were in complete agreement with the determined directions of the electric transition moments of the chromophores. Therefore, 4-substituted aryl triazoles can be used for the determination of the absolute configuration of organic compounds. In addition, the 4-(4-bromophenyl)-1,2,3-triazole allows for red-shifted chromophores to be obtained via Suzuki reactions, thus avoiding overlap with the substrate absorptions.

Heterogenization of chiral mono oxazoline ligands by grafting onto mesoporous silica MCM-41 and their application in copper-catalyzed asymmetric allylic oxidation of cyclic olefins

A series of chiral 4-oxazolinylaniline ligands 8 were conveniently synthesized on a gram scale from inexpensive and commercially available 4-aminobenzoic acid in four steps. The obtained organic chiral ligands have been covalently grafted onto ordered mesoporous silicas MCM-41 and the resulting inorganic–organic hybrid materials have been characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA), powder X-ray diffraction, BET and BJH nitrogen adsorption–desorption methods, energy-dispersive X-ray spectroscopy (EDX), CHN analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). The catalytic and induced asymmetric effects of the chiral copper (I) complexes of these new chiral supported heterogeneous catalysts on the asymmetric allylic oxidation of cycloolefins were investigated under different conditions. Reactions using the catalyst exhibited moderate to good enantioselectivities, up to 80%, and good yields, up to 95% better than the corresponding homogeneous reaction. The catalyst could be recovered easily and reused five times without remarkable loss of reactivity, yield, or enantioselectivity. This is, to the best of our knowledge, the first heterogenization of chiral 4-oxazolinylaniline ligands on an inorganic (silica) surface and their application as a heterogeneous catalyst in the asymmetric Kharash–Sosnovsky reaction.

One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts

Access to enantiomerically pure chiral mono- and disubstituted piperidines and pyrrolidines has been achieved using a biocatalytic cascade involving carboxylic acid reductase (CAR), ω-transaminase (ω-TA), and imine reductase (IRED) enzymes. Starting from keto acids or keto aldehydes, substituted piperidine or pyrrolidine frameworks can be generated in high conversion, ee, and de in one pot, with each biocatalyst exhibiting chemo-, regio-, and/or stereoselectivity during catalysis. The study also includes a systematic investigation of the effect of the position of a methyl group ring substituent on the IRED-catalyzed reduction of a chiral imine. Analysis of the selectivity observed in these reactions revealed an interesting balance between substrate versus enzyme control; the configurations of the products obtained were rationalized on the basis of minimizing 1,3- or 1,2-steric interactions with incoming NADPH.

ChemInform Abstract: New and Efficient Methodology for the Synthesis of Chiral Mono‐ and Ditellurides.

AbstractThe preparation of sodium mono‐ and sodiumditelluride is elaborated.

Enantioselective Recognition of Chiral Carboxylic Acids by a β-Amino Acid and 1,10-Phenanthroline Based Chiral Fluorescent Sensor.

A novel chiral 1,10-phenanthroline-based fluorescent sensor was designed and synthesized from optical active β-amino acids. It used 1,10-phenanthroline moiety as a fluorescent signaling site and binding site, with optically active β-amino acids as a chiral barrier site. Notably, the optically active β-amino acids were obtained by a Lewis base catalyzed hydrosilylation of β-enamino esters according to our former work. The chiral sensor has been used to conduct the enantioselective recognition of chiral mono and dicarboxylic acids derivatives. Using this fluorescent sensor, a moderate “turn-off” fluorescence-diminishment response towards enantiomer of tartaric acids, and proline was observed. It found that l-enantiomers quench the chiral fluorescence sensor more efficiently than d-enantiomers due to the absolute configuration of the β-amino acid.