Metal-centered Chirality Research Articles

Δ-Bis[(S)-2-(4-isopropyl-4,5-di-hydro-oxazol-2-yl)phenolato-κ2 N,O 1](1,10-phenanthroline-κ2 N,N')ruthenium(III) hexa-fluorido-phosphate.

The title compound, [Ru(C12H14NO2)2(C12H8N2)]PF6 crystallizes in the tetra-gonal Sohnke space group P41212. The two bidentate chiral salicyloxazoline ligands and the phenanthroline co-ligand coordinate to the central RuIII atom through N,O and N,N atom pairs to form bite angles of 89.76 (15) and 79.0 (2)°, respectively. The octa-hedral coordination of the bidentate ligands leads to a propeller-like shape, which induces metal-centered chirality onto the complex, with a right-handed (Δ) absolute configuration [the Flack parameter value is -0.003 (14)]. Both the complex cation and the disordered PF6 - counter-anion are located on twofold rotation axes. Apart from Coulombic forces, the crystal cohesion is ensured by non-classical C-H⋯O and C-H⋯F inter-actions.

(η6-Benzene)-chlorido-[(S)-2-(4-isopropyl-4,5-di-hydro-oxazol-2-yl)phenolato]ruthenium(II).

The title compound, [Ru(C12H14NO2)Cl(η6-C6H6)], exhibits a half-sandwich tripod stand structure and crystallizes in the ortho-rhom-bic space group P212121. The arene group is η6 π-coordinated to the Ru atom with a centroid-to-metal distance of 1.6590 (5) Å, with the (S)-2-(4-isopropyl-4,5-di-hydro-oxazol-2-yl)phenolate chelate ligand forming a bite angle of 86.88 (19)° through its N and phenolate O atoms. The pseudo-octa-hedral geometry assumed by the complex is completed by a chloride ligand. The coordination of the optically pure bidentate ligand induces metal centered chirality onto the complex with a Flack parameter of -0.056.

Endowing Metal-Organic Coordination Materials with Chiroptical Activity by a Chiral Anion Strategy.

Recently, chiral metal-organic coordination materials have emerged as promising candidates for a wide range of applications in chiroptoelectronics, chiral catalysis, and information encryption, etc. Notably, the chiroptical effect of coordination chromophores makes them appealing for applications such as photodetectors, OLEDs, 3D displays, and bioimaging. The direct synthesis of chiral coordination materials using chiral organic ligands or complexes with metal-centered chirality is very often tedious and costly. In the case of ionic coordination materials, the combination of chiral anions with cationic, achiral coordination compounds through noncovalent interactions may endow molecular materials with desirable chiroptical properties. The use of such a simple chiral strategy has been proven effective in inducing promising circular dichroism and/or circularly polarized luminescence signals. This concept article mainly delves into the latest advances in exploring the efficacy of such a chiral anion strategy for transforming achiral coordination materials into chromophores with superb photo- or electro-chiroptical properties. In particular, ionic small-molecular metal complexes, metal clusters, coordination supramolecular assemblies, and metal-organic frameworks containing chiral anions are discussed. A perspective on the future opportunities on the preparation of chiroptical materials with the chiral anion strategy is also presented.

Absolute Structure Determination of Chiral Zinc Tartrate MOFs by 3D Electron Diffraction

The absolute structure of the 3D MOF anhydrous zinc (II) tartrate with space group I222 has been determined for both [Zn(L-TAR)] and [Zn(D-TAR)] by electron diffraction using crystals of sub-micron dimensions. Dynamical refinement gives a strong difference in R factors for the correct and inverted structures. These anhydrous MOFs may be prepared phase pure from mild hydrothermal conditions. Powder X-ray diffraction indicates that isostructural or pseudo-isostructural phases can be similarly prepared for several other M2+ = Mg, Mn, Co, Ni and Cu. I222 is a relatively uncommon space group since it involves intersecting two-fold axes that place constraints on molecular crystals. However, in the case of MOFs the packing is dominated by satisfying the octahedral coordination centers. These MOFs are dense 3D networks with chiral octahedral metal centers that may be classed as Δ (for L-TAR) or Λ (for D-TAR).

Post-Modification of Octahedral Chiral-at-Metal Cobalt(III) Complexes by Suzuki–Miyaura Cross-Coupling and Evaluation of Their Catalytic Activity

A family of well-defined Λ- and Δ-configured octahedral cationic chiral-at-cobalt catalysts were expanded through a straightforward postcomplexation of the bromine-functionalized Co(III) complexes based on (R,R)-1,2-cyclohexanediamine and (S,S)-1,2-diphenylethylenediamine by Suzuki–Miyaura cross-coupling reaction (CCR) with arylboronic acids. The corresponding modified Co(III) complexes were isolated by standard silica column chromatography with up to 65% yields. Indeed, it is the first example of the direct modification of the ligand sphere of chiral Co(III) catalysts through Suzuki–Miyaura CCR. It was observed for the first time that the chiral metal center is epimerized during the cross-coupling process at the transmetalation stage on palladium catalyst in the case of minor diastereomers of Co(III) complexes (Δ(R,R)-1 and Λ(S,S)-2). Next, the efficacies of obtained chiral metal-templated complexes 1–4 were evaluated in benchmark asymmetric reactions in order to compare their catalytic activity. Chiral Co(III) complexes 1–4 have been examined as hydrogen bond donor (HBD) catalysts in such important reactions as epoxidation of chalcone and the fixation of CO2 into valuable cyclic carbonates.

Parity Violation Energy of Biomolecules - V: Protein Metal Centers.

The parity-violation difference between mirror images of chiral metal centers found in naturally occurring proteins and enzymes is computed at the Dirac-Hartree-Fock level, for both equilibrium and transition state configurations. The systems, selected on the likelihood of yielding high parity violation energies based on atomic mass and coordination geometry, are extracted from: type I Blue Copper Protein active site, Zn and Cd Carbon Anhydrase, Ni Acetyl-Coenzyme-A Synthase, and Mo based CO-Dehydrogenase. Our values provide an approximate upper limit to possible parity-violation effects in biological systems based on static effects.

Asymmetric catalysis with a chiral-at-osmium complex.

The first example of a chiral osmium catalyst is reported in which the overall chirality originates exclusively from a stereogenic metal center (metal-centered chirality) with all coordinating ligands being achiral. The non-C2-symmetric chiral-at-metal complex contains two cyclometalated 7-methyl-1,7-phenanthrolinium heterocycles which can be described as two chelating pyridylidene remote N-heterocyclic carbene (rNHC) ligands. The octahedral coordination sphere is completed with one CO and one acetonitrile ligand. A monodentate chiral oxazoline ligand is used as a chiral auxiliary ligand to obtain enantiomerically pure chiral-at-osmium complexes (>99 : 1 e.r.). Finally, it is demonstrated that the developed chiral-at-osmium complex is suitable for ring-closing enantioselective C(sp3)-H aminations, including the first example of catalytic enantioselective cyclizations of azidoformates to chiral 2-oxazolidinones.

Regio- and Stereospecific Cyclopolymerization of α,ω-Diynes by Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes.

Both solvent-free and acetonitrile-containing cationic molybdenum imido alkylidene N-heterocyclic carbene (NHC) complexes of the general formula [Mo(NR')(CHCMe2 R)(NHC)(X)+ A- ] (R' = 2,6-Cl2 -C6 H3 , tBu, 2-CF3 -C6 H4 , 2-tBu-C6 H4 , 2,6-iPr2 -C6 H3 , 2,6-Me2 -C6 H3 ; R = Me, Ph; NHC = 1,3-dimesitylimidazol-2-ylidene (IMes), 1,3-di-iPr-imidazol-2-ylidene (IPr), 1,3,5-triphenyl-1,3,4-triazol-2-ylidene); X = CF3 SO3 , C6 F5 O, OCH(CF3 )2 , OC(CF3 )3 , pyrrolide, C6 F5 COO, 2,6-(CF3 )2 -C6 H3 COO; A- = B(ArF )4 - , Al(OC(CF3 )3 )4 - ), have been investigated for their propensity to cyclopolymerize 4,4-disubstituted 1,6-heptadiynes. All metal complexes contain a stereogenic (chiral) metal center, which accounts for the high reactivity and high regioselectivity of insertion (>99%) that are observed for all metal complexes, leading to highly conjugated, α-insertion-derived polyenes that are based on a highly regular polymer backbone and that show absorption maxima close to 600 nm. With the chiral monomer 4-(ethoxycarbonyl)-4-(1S,2R,5S)-(-)-menthoxycarbonyl-1,6-heptadiyne, high syndiospecifity (>99% syndiotactic) is observed. A mechanism explaining the high regio- and stereoselectivity is presented. Thus, α-addition of the monomers proceeds chain-end-controlled trans to the NHC and is preferred over β-addition through intramolecular Mo-O chelation. Insertion of the monomers entails double inversion at the stereogenic metal center in the course of one complete monomer insertion.

Introducing the Chiral Transient Directing Group Strategy to Rhodium(III)-Catalyzed Asymmetric C-H Activation.

The chiral transient directing group (TDG) strategy has been successfully introduced to the rhodium(III)-catalyzed asymmetric C-H activation. In the presence of a catalytic amount of a chiral amine and an achiral rhodium catalyst, various chiral phthalides were synthesized from simple aldehydes with high chemoselectivity, regioselectivity, and enantioselectivity (53 examples, up to 73 % yield and >99 % ee). It is noteworthy that the chiral induction model is different from the previously reported chiral TDG system using amino acid derivatives and palladium salts. The imino group generated in situ from chiral amine and aldehyde acts as the monodentate TDG to promote the C-H activation, stereoselectively generating the chiral rhodacycle bearing a chiral metal center. Moreover, the stereogenic center of the product is created and stereocontrolled during the Grignard-type addition of the C-Rh bond to aldehyde, rather than during the C-H activation step.

Broad-Range Spectral Analysis for Chiral Metal Coordination Compounds: (Chiro)optical Superspectrum of Cobalt(II) Complexes.

Chiroptical broad-range spectral analysis extending from UV to mid-IR was employed to study a family of Co(II) N-(1-(aryl)ethyl)salicylaldiminato Schiff base complexes with pseudotetrahedral geometry associated with chirality-at-metal of the Δ/Λ type. While common chiral organic compounds have well-separated absorption and circular dichroism spectra (CD) in the UV/vis and IR regions, chiral Co(II) complexes feature an almost unique continuum of absorption and CD bands, which cover in sequence the UV, visible, near-IR (NIR), and IR regions of the electromagnetic spectrum. They can be collected in a single (chiro)optical superspectrum ranging from the UV (230 nm, 5.4 eV) to the mid-IR (1000 cm-1, 0.12 eV), which offers a fingerprint of the structure and stereochemistry of the metal complexes. Each region of the superspectrum contributes to one piece of information: the NIR-CD region, in combination with TDDFT calculations, allows a reliable assignment of the metal-centered chirality; the UV-CD region facilitates the analysis of the Δ/Λ diastereomeric equilibrium in solution; and the IR-VCD region contains a combination of low-lying metal-centered electronic states (LLES) and ligand-centered vibrations and displays characteristically enhanced and monosignate VCD bands. Circular dichroism in the NIR and IR regions is crucial to reveal the presence of d-d transitions of the Co(II) core which, due to the electric-dipole forbidden character, would be otherwise overlooked in the corresponding absorption spectra.

Use of a Compact Tripodal Tris(bipyridine) Ligand to Stabilize a Single-Metal-Centered Chirality: Stereoselective Coordination of Iron(II) and Ruthenium(II) on a Semirigid Hexapeptide Macrocycle.

Fe(II)-coordinating hexapeptides containing three 2,2'-bipyridine moieties as side chains were designed and synthesized. A cyclic hexapeptide having three [(2,2'-bipyridin)-5-yl]-d-alanine (d-Bpa5) residues, in which d-Bpa5 and Gly are alternately arranged with 3-fold rotational symmetry, coordinated with Fe(II) to form a 1:1 octahedral Fe(II)-peptide complex with a single facial-Λ configuration of the metal-centered chirality. NMR spectroscopy and molecular dynamics simulations revealed that the Fe(II)-peptide complex has an apparent C3-symmetric conformations on the NMR time scale, while the peptide backbone is subject to dynamic conformational exchange between three asymmetric β/γ conformations and one C3-symmetric γ/γ/γ conformation. The semirigid cyclic hexapeptide preferentially arranged these conformations of the small octahedral Fe(II)-bipyridine complex, as well as the Ru(II) congener, to underpin the single configuration of the metal-centered chirality.

Chiral Phenomena in Multinuclear and Metallosupramolecular Coordination Systems Derived from Metalloligands with Thiol-Containing Amino Acids

Abstract In this account, we focus on the stereochemical and chiral behavior of S-bridged multinuclear and metallosupramolecular coordination compounds that are derived from mononuclear metal complexes with cysteine (H2cys) or penicillamine (H2pen). The mononuclear complexes act as versatile metalloligands with amine and/or carboxyl groups, in addition to the thiol groups, as donor sites, allowing them to form a large variety of coordination compounds in combination with additional metal ions. Several chiral elements, such as chiral metal centers, asymmetric bridging sulfur atoms, and molecular and supramolecular helicity, in addition to asymmetric carbon atoms, are created in the resulting molecular and crystal structures, and their absolute configurations are often controlled to produce a single kind of homochiral species. In addition, this metalloligand approach leads to several unique chiral phenomena, such as stimulus-responsive chiral switching/inversion based on geometrical changes in metal centers, highly efficient chiral recognition between multinuclear complex cations and anions, and unusual spontaneous resolution behavior, in the resulting coordination systems.

Determination of the Molecular Structures of Ferric Enterobactin and Ferric Enantioenterobactin Using Racemic Crystallography.

Enterobactin is a secondary metabolite produced by Enterobacteriaceae for acquiring iron, an essential metal nutrient. The biosynthesis and utilization of enterobactin permits many Gram-negative bacteria to thrive in environments where low soluble iron concentrations would otherwise preclude survival. Despite extensive work carried out on this celebrated molecule since its discovery over 40 years ago, the ferric enterobactin complex has eluded crystallographic structural characterization. We report the successful growth of single crystals containing ferric enterobactin using racemic crystallization, a method that involves cocrystallization of a chiral molecule with its mirror image. The structures of ferric enterobactin and ferric enantioenterobactin obtained in this work provide a definitive assignment of the stereochemistry at the metal center and reveal secondary coordination sphere interactions. The structures were employed in computational investigations of the interactions of these complexes with two enterobactin-binding proteins, which illuminate the influence of metal-centered chirality on these interactions. This work highlights the utility of small-molecule racemic crystallography for obtaining elusive structures of coordination complexes.

Enantioselective Alkynylation of Aromatic Aldehydes Catalyzed by a Sterically Highly Demanding Chiral-at-Rhodium Lewis Acid.

The enantioselective catalytic alkynylation of aromatic aldehydes is reported using a sterically highly hindered bis-cyclometalated rhodium-based Lewis acid catalyst featuring the octahedral metal as the only stereogenic center. Yields of 58-98% with 79-98% enantiomeric excess were achieved using 1-2 mol % of catalyst. This work complements previous work from our laboratory on the enantioselective alkynylation of 2-trifluoroacetyl imidazoles (Chem. - Eur. J. 2016, 22, 11977-11981) and trifluoromethyl ketones (J. Am. Chem. Soc. 2017, 139, 4322-4325) using catalysts with octahedral metal-centered chirality.

Stereogenic-Only-at-Metal Asymmetric Catalysts.

Chirality is an essential feature of asymmetric catalysts. This review summarizes asymmetric catalysts that derive their chirality exclusively from stereogenic metal centers. Reported chiral-at-metal catalysts can be divided into two classes, namely, inert metal complexes, in which the metal fulfills a purely structural role, so catalysis is mediated entirely through the ligand sphere, and reactive metal complexes. The latter are particularly appealing because structural simplicity (only achiral ligands) is combined with the prospect of particularly effective asymmetric induction (direct contact of the substrate with the chiral metal center). Challenges and solutions for the design of such reactive stereogenic-only-at-metal asymmetric catalysts are discussed.

Understanding Rate Acceleration and Stereoinduction of an Asymmetric Giese Reaction Mediated by a Chiral Rhodium Catalyst.

The surprising acceleration of the addition of electron-rich radicals to α,β-unsaturated 2-acyl imidazoles by a chiral-at-metal rhodium catalyst is investigated. M06/Lanl2DZ (Rh),6-31G(d) calculations reproduce the observed rate acceleration and shed light on a catalyst design where a rigid chiral pocket with a steric interaction >5 Å from the chiral metal center leads to the observed high stereoinduction. Analysis of the molecular orbitals of two key addition transition states emphasize the role of the catalyst as a Lewis acid without significant charge transfer.

Exclusive Metal-Centered Chirality for Asymmetric Catalysis

Exclusive Metal-Centered Chirality for Asymmetric Catalysis

(Invited) Stereodivergent-at-Metal Synthesis of [60]Fullerene Hybrids

The preparation of chiral metal complexes and, specifically, chiral at metal complexes, is a highly sought after goal in current organometallic chemistry due to its relevance in enantioselective metal-mediated processes.1. Despite the wealth of metal-fullererene hybrids reported to date, only a few are optically actives.2 To the best of our knowledge, only a single case presents a stereogenic metal center,3 while in all of them the chiral information stems from the stoichiometric use of other chiral ligands.4 In this regard, the use of asymmetric organo- and metal-catalysis in fullerene chemistry has provided an easy access to optically active derivatives through a precise stereocontrol in the newly formed asymmetric carbon atoms.5 Conversely, the control of the metal-centered chirality is not a trivial issue due to the configurational lability of the metals that often undergo rapid ligands exchange.1 In this communication, we report the first enantioselective synthesis of fullerene hybrids endowed with a stable stereogenic metal center whose configuration can be defined at will by the proper chiral catalyst choice. In these reactions, iridium, rhodium and ruthenium pyrrolidino[3,4:1,2][60]fullerene half-sandwich complexes with four new stereocenters are formed, namely the two C-2 and C-5 chiral car bons at the pyrrolidine ring, the asymmetric nitrogen atom and the transition metal center (Scheme). The suitable functionalization and stereochemistry of the chiral fullerene ligand determine the final configuration of the metal center. Interestingly, the chiral metal center does not undergo any epimerization process as evidenced by temperature dependent NMR analysis as well as by DFT theoretical calculations.6 References B. Bauer, Chem. Soc. Rev. 2012, 41, 3153-3167.L. Balch, M. M. Olmstead, Chem. Rev. 1998, 98, 2123-2166.Y.-W. Zhong, Y. Matsuo, E. Nakamura, Chem. Asian J. 2007, 2, 358-366.V. I. Sokolov, V. V. Bashilov, F. M. Dolgushin, N. V. Abramova, K. K. Babievsky, A. G. Ginzburg, P. V. Petrovskii, Tetrahedron Lett. 2009, 50, 5347-5350.a) S. Filippone, E. E. Maroto, A. Martín-Domenech, M. Suárez, N. Martín, Nat. Chem. 2009, 1, 578-582; b) E. E. Maroto, M. Izquierdo, S. Reboredo, J. Marco-Martínez, S. Filippone, N. Martín, Acc. Chem. Res. 2014, 47, 2660-2670.J. Marco-Martínez, S. Vidal, I. Fernández, S. Filippone, N. Martín, Angew. Chem. Int. Ed., 2017, accepted for publication.

Three-Component Asymmetric Mannich Reaction Catalyzed by a Lewis Acid with Rhodium-Centered Chirality.

A highly efficient direct asymmetric three-component Mannich reaction of an N-acylpyrazole, an aldehyde and a primary or secondary amine, was enabled by a rhodium-based Lewis-acid catalyst with metal-centered chirality. Excellent enantioselectivities were achieved for a variety of substrates at a typical catalyst loading of merely 0.5 mol % (23 examples, up to 98 % ee).

Stereocontrolled self-assembly of luminescent lanthanide helicates and their enantiodifferentiation using Δ-TRISPHAT as the NMR resolving agent

Self-assembled supramolecular lanthanide constructs have great potential in luminescent bioprobes/sensors. Stereoselectivity on the lanthanide assemblies is needed to facilitate chiroptical probes and sensors. Herein we report the stereocontrolled synthesis of M2L3-type (M=metal ion, L=organic ligand) lanthanide triple-helicates using a chiral-induction strategy, where the periphery point-chirality [(R,R) or (S,S)] of the organic ligands was transferred into the metal centered chirality (ΔΔ or ΛΛ), thus leading to the formation of topological chiral (P or M) helicates. Moreover, commercially available Δ-TRISPHAT proved to be an effective NMR chiral resolving agent to differentiate between the two enantiomers of the helicate.