Chiral Complexes Research Articles

Synthesis and Characterization of Statistical and Block Copolymers of n-Hexyl Isocyanate and 3-(Triethoxysilyl) Propyl Isocyanate via Coordination Polymerization.

Well-defined statistical copolymers of n-hexyl isocyanate, HIC, and 3-(triethoxysilyl)propyl isocyanate, TESPI, were synthesized via coordination polymerization mechanism, employing a chiral half-titanocene complex as initiator. The monomer reactivity ratios of the statistical copolymers were calculated using linear graphical methods and the computer program COPOINT in the frame of the terminal model. The molecular and structural characteristics of the copolymers were also calculated. The kinetics of the thermal decomposition of the statistical copolymers was studied by Thermogravimetric Analysis, TGA, and Differential Thermogravimetry, DTG, and the activation energy of this process was calculated employing several theoretical models. In addition, block copolymers constituted from PHIC and PTESPI blocks were synthesized by sequential coordination polymerization. All samples were characterized by nuclear magnetic resonance, NMR, spectroscopy and size exclusion chromatography, SEC. The thermal stability of the blocks was also studied by TGA and DTG and compared to the corresponding statistical copolymers.

Redox Activity of IrIII Complexes with Multidentate Ligands Based on Dipyrido-annulated N-Heterocyclic Carbenes: Access to High Valent and High Spin State with Carbon Donors.

Synthetic strategies to access high-valent iridium complexes usually requireuse of π donating ligands bearing electronegative atoms (e.g. amide or oxide) or σ donating electropositive atoms (e.g. boryl or hydride). Besides the η5-(methyl)cyclopentadienyl derivatives, high-valent η1 carbon-ligated iridium complexes are challenging to synthesize. To meet this challenge, this work reports the oxidation behavior of an all-carbon-ligated anionic bis(CCC-pincer) IrIII complex. Being both σ and π donating, the diaryl dipyrido-annulated N-heterocyclic carbene (dpa-NHC) IrIII complex allowed a stepwise 4e- oxidation sequence. The first 2e- oxidation led to an oxidative coupling of two adjacent aryl groups, resulting in formation of a cationic chiral IrIII complex bearing a CCCC-tetradentate ligand. A further 2e- oxidation allowed isolation of a high-valent tricationic complex with a triplet ground state. These results close a synthetic gap for carbon-ligated iridium complexes and demonstrate the electronic tuning potentialof organic π ligands for unusual electronic properties.

Biologically Active Palladium(II), Zinc(II), and Copper(II) Complexes with Terpene Ligands as Potential Pharmaceutical Drugs

A final review of the results of studies of versatile biological activities (in vitro) of chiral metal complexes with benzylamine and ethylenediamine derivatives of terpenes is presented. The cytotoxic profiles of palladacycles containing a Pd–C bond and palladium and zinc chelate complexes were determined. For a number of compounds, the possible mechanisms of potential anticancer action were analyzed, such as modulation of mitochondrial functioning and effect on the parameters of glycolytic function of tumor cells. The antibacterial and antifungal activities of palladium complexes of different types and copper chelate complexes were investigated. A correlation between high antimicrobial activity and antioxidant properties was found for a number of copper complexes. The material is supplemented by an extended analysis of publications in relevant subjects.

Asymmetric Hydrogenation of Tetrapyridine‐Type N‐Heteroarenes Using Phosphine‐Free Ruthenium Diamine Catalysts†

Comprehensive SummaryChiral ruthenium‐catalyzed enantioselective hydrogenation of tetrapyridine‐type N‐heteroarenes was firstly developed. The partial reduction of adjacent tetraheteroaromatic substrates proceeded smoothly in the presence of phosphine‐free chiral cationic ruthenium diamine complexes, affording unprecedented high reactivity, enantioselecitivity and diastereoselectivity (up to 93% yield, >99% ee and 92 : 8 dr). The potential application of chiral tetradentate pyridine‐amine products as chiral ligands has been demonstrated in the Cu‐catalyzed asymmetric Friedel–Crafts alkylation reaction between indoles and nitroalkenes.

Cobalt(II)-Catalyzed Enantioselective Propargyl Claisen Rearrangement: Access to Allenyl-Substituted Quaternary β-Ketoesters.

Highly enantioselective propargyl Claisen rearrangement of O-propargyl β-ketoesters was achieved under 2.5 mol % of the chiral cobalt complex as the catalyst under mild reaction conditions. With Co(OTf)2 as the Lewis acid and C1-symmetric imidazoline-pyrroloimidazolone pyridine as the ligand, diverse chiral allenyl-substituted all-carbon quaternary β-ketoesters were obtained in good yields (up to 97% yield) and high enantioselectivities (up to 98% ee).

Advances in Versatile Chiral Ligands for Asymmetric Gold Catalysis

The formation of valuable chiral skeletons through asymmetric gold catalysis has made considerable progress due to the unrivaled affinity of gold complexes with multiple carbon–carbon bonds. The renaissance of chiral ligands in recent decades has enabled the elaborate design of chiral gold complexes, which are of great significance to control chiral formation in these catalytic reactions. Therefore, this review intends to highlight the design and central role of versatile chiral ligands in asymmetric gold catalysis. Specifically, the seminal applications of various chiral ligands with representative examples in various gold-catalyzed asymmetric reactions are comprehensively explored. In addition, the reaction mechanisms are mentioned when the crucial interactions between ligands and activated substrates are introduced. Furthermore, the applications of enantioselective gold catalysis in the construction of chiral functional organic materials and drug molecules are also presented.

Cu‐Catalyzed Site‐ and Enantioselective Borylcyanation of 1,2‐Disubstituted Aryl Alkenes

AbstractA catalytic chemo‐ and enantioselective generation of secondary benzylic copper complexes from Cu−B(pin) (pin=pinacolato) additions to 1,2‐disubstituted aryl alkenes followed by in situ site selective cyanation at either aryl group or benzylic position to construct multifunctional alkylboron compounds is presented. The method is distinguished by identification of chiral Cu complexes leading to not only high enantioselectivity but also better efficiency compared with achiral catalysts. In addition, an unprecedented mode of cyanation at benzylic site through dearomative isomerization was disclosed. Functionalization of multifunctional alkylboron products provides useful building blocks that are otherwise difficult to access.

Diastereodivergent and Enantioselective Synthesis of Homoallylic Alcohols via Nickel-Catalyzed Borylative Coupling of 1,3-Dienes with Aldehydes.

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

Exploration of chiral drugs as references for chiral discrimination of valsartan and voriconazole by tandem mass spectrometry.

The use of mass spectrometry for chiral recognition and quantification has attracted great interest owing to its speed, sensitivity, specificity, and tolerance. However, searching for chiral selectors in chiral analyses using mass spectrometry is still problematic. In this study, chiral drugs could be applied as references for the chiral recognition and enantiomeric quantification of valsartan and voriconazole. Two novel pairs of metal-bound diastereomeric complex ions were detected by mass spectrometry, namely, nickel (II)-bound dimeric ions [NiII (2R,5S-emtricitabine) (S-valsartan)-H]+ and [NiII (2R,5S-emtricitabine) (R-valsartan)-H]+ and copper (II)-bound dimeric ions [CuII (S,S,S-enalaprilat) (2S,3R-voriconazole)-H]+ and [CuII (S,S,S-enalaprilat) (2R,3S-voriconazole)-H]+ . The resulting diastereomers were successfully identified based on the relative intensities of their characteristic fragments using tandem mass spectrometry. The logarithm of the characteristic fragment ion abundance ratio exhibited a good linear relationship with the enantiomeric excess. Density functional theory calculations were also performed to elucidate the mechanism of the structural differences observed in the MS results. This established approach proves that chiral drugs can serve as ligands for the rapid recognition and quantitative analysis of other chiral drugs without a chiral chromatographic column or complex sample pretreatment.

The Role of the CuCl Active Complex in the Stereoselectivity of the Salt-Induced Peptide Formation Reaction: Insights from Density Functional Theory Calculations.

The salt-induced peptide formation (SIPF) reaction is a prebiotically plausible mechanism for the spontaneous polymerization of amino acids into peptides on early Earth. Experimental investigations of the SIPF reaction have found that in certain conditions, the l enantiomer is more reactive than the d enantiomer, indicating its potential role in the rise of biohomochirality. Previous work hypothesized that the distortion of the CuCl active complex toward a tetrahedral-like structure increases the central chirality on the Cu ion, which amplifies the inherent parity-violating energy differences between l- and d-amino acid enantiomers, leading to stereoselectivity. Computational evaluations of this theory have been limited to the protonated-neutral l + l forms of the CuCl active complex. Here, density functional theory methods were used to compare the energies and geometries of the homochiral (l + l and d + d) and heterochiral (l + d) CuCl-amino acid complexes for both the positive-neutral and neutral-neutral forms for alanine, valine, and proline. Significant energy differences were not observed between different chiral active complexes (i.e., d + d, l + l vs. l + d), and the distortions of active complexes between stereoselective systems and non-selective systems were not consistent, indicating that the geometry of the active complex is not the primary driver of the observed stereoselectivity of the SIPF reaction.

Light-enabled deracemization of cyclopropanes by Al-salen photocatalysis.

Privileged chiral catalysts-those that share common structural features and are enantioselective across a range of reactions-continue to transform the chemical-research landscape1. In recent years, new reactivity modes have been achieved through excited-state catalysis, processes activated by light, but it is unclear if the selectivity of ground-state privileged catalysts can be matched. Although the interception of photogenerated intermediates by ground-state cycles has partially addressed this challenge2, single, chiral photocatalysts that simultaneously regulate reactivity and selectivity are conspicuously scarce3. So far, precision donor-acceptor recognition motifs remain crucial in enantioselective photocatalyst design4. Here we show that chiral Al-salen complexes, which have well-defined photophysical properties, can be used for the efficient photochemical deracemization5 of cyclopropyl ketones (up to 98:2 enantiomeric ratio (e.r.)). Irradiation at λ = 400 nm (violet light) augments the reactivity of the commercial catalyst to enable reactivity and enantioselectivity to be regulated simultaneously. This circumvents the need for tailored catalyst-substrate recognition motifs. It is predicted that this study will stimulate a re-evaluation of many venerable (ground-state) chiral catalysts in excited-state processes, ultimately leading to the identification of candidates that may be considered 'privileged' in both reactivity models.

Circular Dichroism Spectroscopic Studies on Solution Chemistry of M(II)-Monensinates in Their Competition Reactions

The chirality of the polyether ionophore monensic acid A can be successfully used to study its coordination ability in solution. A complementary approach to gain new insights into the complexation chemistry of the antibiotic (studied previously by circular dichroism (CD) spectroscopy in the ultraviolet range (UV-CD)) is presented. (1) Methods: The CD spectroscopy in the visible (VIS-CD) and near-infrared (NIR-CD) range is applied to evaluate the affinity of deprotonated monensic acid A (monensinate A) towards Ni(II) or Co(II) cations in methanolic solution. Competition experiments between a variety of colorless divalent metal ions for binding the ligand anion were also performed. (2) Results: The stability constants of the species observed in binary Ni(II)/Co(II)-monensinate systems and their distribution were reevaluated with the VIS- and NIR-CD techniques. The data confirmed the formation of mono and bis complexes depending on the metal-to-ligand molar ratio. The studies on the systems containing two competing divalent metal cations exclude the formation of ternary complex species but provide an opportunity to also calculate the stability constants of Zn(II), Mg(II), and Ca(II) monensinates. (3) Conclusions: The advantages of CD spectroscopy in the VIS-NIR range (“invisible” ligand and metal salts, “visible” chiral complex species) simplify the experimental dataset evaluation and increase the reliability of computed results.

Switching Regioselectivity in the Asymmetric Bromocyclization of Difluoroalkenes Catalyzed by a Chiral Bisphosphine Oxide

AbstractWe present an efficient approach for the enantioselective synthesis of difluoromethylene-containing oxazine compounds through 6-endo-selective bromocyclization of difluoroalkenes by using a chiral proton-bridged bisphosphine oxide complex as a catalyst precursor. The regioselectivity is significantly influenced by the solvent and the catalyst structure, and 6-endo cyclization products can be obtained preferentially with moderate to high enantioselectivity. This protocol offers complementary regioselectivity to our previously reported 5-exo-selective reaction, permitting the synthesis of diverse medicinally interesting compounds.

Color Tunable Circularly Polarized Luminescence Properties of Chiral Platinum(II) Complexes with Salen Ligands

Abstract A series of novel chiral platinum complexes 1–8 (R = 4-NEt2 (1), 4-F (2), 5-CF3 (3), 5-Cl (4), 5-OCF3 (5), 4-CF3 (6), 5-F (7), 5-MeO (8)) was prepared and their circularly polarized luminescence (CPL) properties were compared with those of the non-substituted analogue 9 (R = H). The complexes showed multi-color (green, yellow, and red) phosphorescence in the solution state, depending on the substitution position of the functional group of the ligands. The chiral complexes exhibited CPL with absolute luminescence dissymmetry factor (glum) of up to the 1.3 × 10−3 in the dilute solution state. Acid-induced CPL was also achieved by the protonation of the diethylamino group of complex 1 with CH3SO3H. Density functional theory (DFT) calculations were conducted to further understand the structure dependence of the chromogenic behavior of these complexes.

Synthesis, crystal structure, and intrinsic reactivity descriptors of coordination complexes of [(cis-PdCl2·L-proline) L-proline] and [trans-PdCl2·(glycine-OMe)2

This work describes the synthesis and structural characterization of two palladium (II) complexes elucidated by infrared spectroscopy, dispersive energy analysis (EDS) with Scanning Electron Microscopy (SEM) and X-ray single-crystal diffraction analysis. The first chiral complex is derivatized from l-proline amino acid, obtaining [Cis-PdCl2·L-proline(L-proline)] (1), in which the structure does not have symmetry elements and crystallized in a triclinic crystal system on a non-centrosymmetric space group P1. The comparison with the structural complex of [trans-PdCl2·(glycine-OMe)2] (3) becomes necessary due to the anticancer activity of its analog, cis-platinum, and the catalytic activity caused by Pd as a metallic center. Complex 1 is therefore made up of a free proline molecule linked by a single hydrogen bond to a PdCl2 molecule forming a 5-member chelate ring of the COO···Pd···NH type with another proline molecule and displaying distorted angles and bond sizes to the square planar geometry of the palladium (Pd) center. Ring formation generates a new stereogenic center chemically correlated with the induction caused by the absolute configuration S of the initial amino acid. The crystal results strongly indicate the confirmed configuration by the Flack parameter and its crystal packing stabilization by an intermolecular H-bond network, highlighting as a secondary mimicking structure the β sheets formed by hydrogen bonding interaction of the N—H···Cl type responsible for the disorder moldered on pyrrolidine ring.Furthermore, the Pd(II) complex obtained by the glycine was [trans-PdCl2·(glycine-OMe)2] (3). Regarding its chemical structure, this complex is constituted by the union of two glycine methyl ester molecules binding to a Pd in a trans disposition concerning the almost perfect square plane, which also contains a C2 axis of rotation. Complex 3 crystallized in a monoclinic system and centrosymmetric space group P21/c, the packing is favored by four strong hydrogen bond type interactions presenting helices with 90° rotations between each layer.Owing to their great interest and relevance in Pd—N amino acid in catalytic and medicinal chemistry, the electronic and global reactivity properties of complexes 1 and 3 were further explored by computational methods in the framework of Density Functional Theory, finding 1 as the most reactive complex due to the narrower E-LUMO/E-HOMO energy gap, having this band gap in agreement with the lowest hardness value compared to those shown for 3, in which band gap and hardness are higher with a tendency to kinetic stability and controlled reactivity.

Chiral Zn3Ln3 Hexanuclear Clusters of an Achiral Flexible Ligand.

Multifunctional single-molecule magnets (SMMs) have sparked great interest, but chiral SMMs obtained via spontaneous resolution are rarely reported. We synthesized a series of chiral trinuclear hepta-coordinate lanthanide complexes [ZnII3LnIII3] (1 for Dy, 2 for Tb, 3 for Gd, and 4 for Dy0.07Y0.93) using the achiral flexible ligand H2L (2,2'-[1,2-ethanediylbis[(ethylimino)methylene]]bis[3,5-dimethylphenol]). The complexes crystallize in the chiral P63 group space, and two enantiomers of different chirality are spontaneously resolved. Three [Zn(L)Cl]- anions utilize the two phenoxy oxygen atoms of each L2- to coordinate with three lanthanide ions, respectively, and the three hepta-coordinate D5h lanthanide ions are arranged in a triangle. The chirality comes from the propeller arrangement of the peripheral three bidentate chelate L2- ligands like octahedral [M(AA)3]n+/- (M = transition metal ions; AA = bidentate chelate ligands, e.g., 2,2'-bipyridine, 1,10-phenathroline, ethylenediamine, acac- or oxalate). Complex 1 exhibits an AC susceptibility signal and is frequency-dependent, which is typical of SMMs. Complex 4, doped with a large amount of diamagnetic Y(III) in Dy(III), exhibits Ueff = 48.3 K and τ0 = 4.4 × 10-8 s in experiments. Complex 2 shows circularly polarized luminescence and apparent photoluminescence, typical of the f-f transitions of Tb(III).

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2) and Pd(II) complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99% ee) and diastereoselectivity (up to >20:1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as ∆6-protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the Pd(II) complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems

AbstractAn asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD‐NH2) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6‐protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD‐NH2 catalyst and the branched chain of the substrate, hydrogen‐bonding interactions between the N−H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

Chiral Metal Salen Complexes as Chiral Electrocatalysts for Asymmetric Electrochemical Carboxylation of Acetophenone

AbstractAsymmetric electrochemical carboxylation is the direct and effective method to fix and utilize CO2, and the selection of chiral catalysts is crucial. In this paper, a series of chiral metal salen complexes are prepared as chiral catalysts to achieve enantioselective conversion of acetophenone with CO2 to synthesis chiral 2‐hydroxy‐2‐phenylpropionic acid under electrochemical conditions. Under the catalysis of NiIIL1, the enantiomeric excess (ee) value of 90 % and yield of 59 % are obtained. By cyclic voltammetry and potentiostatic electrolysis, the effects of metal centers and tert‐butyl groups in ligand structures on the catalytic results are studied and the possible reaction mechanism is proposed.

Chiral Organocatalysts in Enantioselective CO2 Utilization Reactions

AbstractThe development of efficient CO2 utilization reactions has gained a significant amount of attention in recent years. Although transformations of CO2 to produce basic chemicals have been extensively investigated, the development of catalytic enantioselective CO2 utilization reactions for the preparation of fine chemicals remains limited at this stage. Several excellent methods for catalytic enantioselective CO2 utilization using chiral metal complex catalysts have been reported. Many researchers have also focused on developing organocatalyzed approaches to enantioselective CO2 utilization, and several excellent examples have appeared in recent years. Herein, recent advances in catalytic enantioselective CO2 utilization reactions using chiral organocatalysts are reviewed to provide a forecast for organocatalyzed enantioselective CO2 utilization research.