Synthesis of Cross-Chain Bridging Cryptands and Induction of Molecular Chirality.

In this study, we synthesized two cryptands featuring entangled tri- and tetra(ethylene glycol) linkers. The cryptand bearing short linkers was chiral without any asymmetric carbon atoms. After chiral high-performance liquid chromatography was used to separate the enantiomers, the absolute configuration of each cryptand was determined through single-crystal X-ray and circular dichroism analyses. The racemization of the cryptand possessing long linkers proceeded at room temperature.

Counteranion-induced structural isomerization of phosphine-protected PdAu8 and PtAu8 clusters.

Controlling the geometric structures of metal clusters through structural isomerization allows for tuning of their electronic state. In this study, we successfully synthesized butterfly-motif [PdAu8(PPh3)8]2+ (PdAu8-B, B means butterfly-motif) and [PtAu8(PPh3)8]2+ (PtAu8-B) by the structural isomerization from crown-motif [PdAu8(PPh3)8]2+ (PdAu8-C, C means crown-motif) and [PtAu8(PPh3)8]2+ (PtAu8-C), induced by association with anionic polyoxometalate, [Mo6O19]2- (Mo6) respectively, whereas their structural isomerization was suppressed by the use of [NO3]- and [PMo12O40]3- as counter anions. DR-UV-vis-NIR and XAFS analyses and density functional theory calculations revealed that the synthesized [PdAu8(PPh3)8][Mo6O19] (PdAu8-Mo6) and [PtAu8(PPh3)8][Mo6O19] (PtAu8-Mo6) had PdAu8-B and PtAu8-B respectively because PdAu8-Mo6 and PtAu8-Mo6 had bands in optical absorption at the longer wavelength region and different structural parameters characteristic of the butterfly-motif structure obtained by XAFS analysis. Single-crystal and powder X-ray diffraction analyses revealed that PdAu8-B and PtAu8-B were surrounded by six Mo6 with rock salt-type packing, which stabilizes the semi-stable butterfly-motif structure to overcome high activation energy for structural isomerization.

Rational Supramolecular Strategy via Halogen Bonding for Effective Halogen Recognition in Molecular Imprinting.

Halogen bonding is a highly directional interaction and a potential tool in functional material design through self-assembly. Herein, we describe two fundamental supramolecular strategies to synthesize molecularly imprinted polymers (MIPs) with halogen bonding-based molecular recognition sites. In the first method, the size of the σ-hole was increased by aromatic fluorine substitution of the template molecule, enhancing the halogen bonding in the supramolecule. The second method involved sandwiching hydrogen atoms of a template molecule between iodo substituents, which suppressed competing hydrogen bonding and enabled multiple recognition patterns, improving the selectivity. The interaction mode between the functional monomer and the templates was elucidated by 1H NMR, 13C NMR, X-ray absorption spectroscopy, and computational simulation. Finally, we succeeded in the effective chromatographic separation of diiodobenzene isomers on the uniformly sized MIPs prepared by multi-step swelling and polymerization. The MIPs selectively recognized halogenated thyroid hormones via halogen bonding and could be applied to screening endocrine disruptors.

Continuous-Flow Suzuki-Miyaura Coupling in Water and Organic Solvents Promoted by Blends of Stabilized Convoluted Polymeric Palladium Catalysts and Polymeric Auxiliary Materials.

Given that heterogeneous palladium-catalyzed C-C bond formation reactions under continuous-flow conditions are well suited for the efficient and safe production of pharmaceuticals and functional materials, the development of active and durable catalysts for this purpose is a matter of high practical significance. Here, a previously established molecular convolution methodology was used to synthesize catalysts for Suzuki-Miyaura coupling under flow conditions by blending convoluted polymeric palladium catalysts (prepared from copolymers of 4-vinylpyridine and 4-tert-butylstyrene) and crosslinked polymeric auxiliary materials (prepared from copolymers of divinylbenzene and 4-tert-butylstyrene). The optimal catalyst exhibited high performance and durability and allowed numerous biaryl products such as liquid-crystalline materials, organic electroluminescent materials, and pharmaceuticals to be continuously synthesized with turnover frequencies of up to 238 h-1 . In a demonstration of practical utility, the developed catalytic system was used for the continuous synthesis of two pharmaceuticals (felbinac and fenbufen) in water as the sole solvent.

Stacking of a Cofacially Stacked Iron Phthalocyanine Dimer on Graphite Achieved High Catalytic CH4 Oxidation Activity Comparable to That of pMMO.

Numerous biomimetic molecular catalysts inspired by methane monooxygenases (MMOs) that utilize iron or copper-oxo species as key intermediates have been developed. However, the catalytic methane oxidation activities of biomimetic molecule-based catalysts are still much lower than those of MMOs. Herein, we report that the close stacking of a µ-nitrido-bridged iron phthalocyanine dimer onto a graphite surface is effective in achieving high catalytic methane oxidation activity. The activity is almost 50 times higher than that of other potent molecule-based methane oxidation catalysts and comparable to those of certain MMOs, in an aqueous solution containing H2O2. It was demonstrated that the graphite-supported µ-nitrido-bridged iron phthalocyanine dimer oxidized methane, even at room temperature. Electrochemical investigation and density functional theory calculations suggested that the stacking of the catalyst onto graphite induced partial charge transfer from the reactive oxo species of the µ-nitrido-bridged iron phthalocyanine dimer and significantly lowered the singly occupied molecular orbital level, thereby facilitating electron transfer from methane to the catalyst in the proton-coupled electron-transfer process. The cofacially stacked structure is advantageous for stable adhesion of the catalyst molecule on the graphite surface in the oxidative reaction condition and for preventing decreases in the oxo-basicity and generation rate of the terminal iron-oxo species. We also demonstrated that the graphite-supported catalyst exhibited appreciably enhanced activity under photoirradiation owing to the photothermal effect.

Separation of Glycoproteins Based on Sugar Chains Using Novel Stationary Phases Modified with Poly(ethylene glycol)-Conjugated Boronic-Acid Derivatives.

Boronic acid (BA) reversibly complexes with the diol structure. BA derivatives separate glycoproteins based on the differences in the sugar chains. Separation typically occurs under basic conditions, which does not guarantee the structural stability of glycoproteins. Here, 5-boronopicolinic acid (BPA) is used to prepare silica-gel based columns with poly(ethylene glycol) (PEG) as a linker to suppress nonselective adsorption and poly(ethylene imine) (PEI) as a scaffold to increase the BPA moiety density. High-performance liquid chromatography (HPLC) using only aqueous buffer solutions without organic solvents demonstrates the selective retention ability of the BPA columns for glycoproteins. BPA interacts with the diols in the sugar chains but not the proteins. In an evaluation for N-glycans, the BPA columns show a higher retention ability toward high mannose type and a lower affinity to N-acetylneuraminic acid (Neu5Ac). Finally, a pair of glycoproteins, fetuin and asialofetuin, are selectively separated due to the presence of Neu5Ac on the nonreducing end.

Four- and two-armed hetero porphyrin dimers: their specific recognition and self-sorting behaviours.

In this study we self-assembled the four-armed porphyrin hetero dimer capsule Cap4, stabilized through amidinium-carboxylate salt bridges, in CH2Cl2 and CHCl3. The dimer capsule Cap4 was kinetically and thermodynamically more stable than the corresponding two-armed dimer Cap2. The number of arms strongly influenced their recognition behaviour; guests possessing small aromatic faces (e.g., 1,3,5-trinitrobenzene) preferred residing in the cavity of the two-armed capsule Cap2, rather than in Cap4, both thermodynamically and kinetically; in contrast, large aromatic guests (e.g., 9,10-dibromoanthracene) were encapsulated predominantly by Cap4 because of favourable entropic effects. The number of arms enabled self-sorting behaviour of the dimer formation; complexation studies using an equimolar mixture of the four porphyrin constituents of the two capsules revealed the quantitative formation of the corresponding dimers Cap2 and Cap4. Furthermore, we examined the specific molecular recognition of Cap2 and Cap4; NMR experiments of mixtures of Cap2 and Cap4 in the presence of favourable guests for Cap2 and Cap4 revealed that these guest molecules were encapsulated selectively by their preferred hosts.

Synthesis of a Mechanically Planar Chiral and Axially Chiral [2]Rotaxane.

In this study, we synthesized a [2]rotaxane that was both mechanically planar chiral and axially chiral, comprising a symmetrical bis-crown ether featuring a biphenyl moiety (as the macrocyclic component) and a symmetrical bis-ammonium salt (as the dumbbell-shaped component).

Mechanochemical synthesis of magnesium-based carbon nucleophiles in air and their use in organic synthesis.

Since the discovery of Grignard reagents in 1900, the nucleophilic addition of magnesium-based carbon nucleophiles to various electrophiles has become one of the most powerful, versatile, and well-established methods for the formation of carbon-carbon bonds in organic synthesis. Grignard reagents are typically prepared via reactions between organic halides and magnesium metal in a solvent. However, this method usually requires the use of dry organic solvents, long reaction times, strict control of the reaction temperature, and inert-gas-line techniques. Despite the utility of Grignard reagents, these requirements still represent major drawbacks from both an environmental and an economic perspective, and often cause reproducibility problems. Here, we report the general mechanochemical synthesis of magnesium-based carbon nucleophiles (Grignard reagents in paste form) in air using a ball milling technique. These nucleophiles can be used directly for one-pot nucleophilic addition reactions with various electrophiles and nickel-catalyzed cross-coupling reactions under solvent-free conditions.

Microwave-assisted photooxidation of sulfoxides.

We demonstrated microwave-assisted photooxidation of sulfoxides to the corresponding sulfones using ethynylbenzene as a photosensitizer. Efficiency of the photooxidation was higher under microwave irradiation than under conventional thermal heating conditions. Under the conditions, ethynylbenzene promoted the oxidation more efficiently than conventional photosensitizers benzophenone, anthracene, and rose bengal. Ethynylbenzene, whose T1 state is extremely resistant to intersystem crossing to the ground state, was suitable to this reaction because spectroscopic and related reported studies suggested that this non-thermal effect was caused by elongating lifetime of the T1 state by microwave. This is the first study in which ethynylbenzene is used as a photosensitizer in a microwave-assisted photoreaction.

Thermal stability of crown-motif [Au9(PPh3)8]3+ and [MAu8(PPh3)8]2+ (M = Pd, Pt) clusters: Effects of gas composition, single-atom doping, and counter anions.

The thermal behaviors of ligand-protected metal clusters, [Au9(PPh3)8]3+ and [MAu8(PPh3)8]2+ (M = Pd, Pt) with a crown-motif structure, were investigated to determine the effects of the gas composition, single-atom doping, and counter anions on the thermal stability of these clusters. We successfully synthesized crown-motif [PdAu8(PPh3)8][HPMo12O40] (PdAu8-PMo12) and [PtAu8(PPh3)8][HPMo12O40] (PtAu8-PMo12) salts with a cesium-chloride-type structure, which is the same as the [Au9(PPh3)8][PMo12O40] (Au9-PMo12) structure. Thermogravimetry-differential thermal analysis/mass spectrometry analysis revealed that the crown-motif structure of Au9-PMo12 was decomposed at ∼475 K without weight loss to form Au nanoparticles. After structural decomposition, the ligands were desorbed from the sample. The ligand desorption temperature of Au9-PMo12 increased under 20% O2 conditions because of the formation of Au nanoparticles and stronger interaction of the formed O=PPh3 than PPh3. The Pd and Pt single-atom doping improved the thermal stability of the clusters. This improvement was due to the formation of a large bonding index of M-Au and a change in Au-PPh3 bonding energy by heteroatom doping. Moreover, we found that the ligand desorption temperatures were also affected by the type of counter anions, whose charge and size influence the localized Coulomb interaction and cluster packing between the cationic ligand-protected metal clusters and counter anions.

Iron-catalysed enantioselective carbometalation of azabicycloalkenes.

The first enantioselective carbometalation reaction of azabicycloalkenes has been achieved by iron catalysis to in situ form optically active organozinc intermediates, which are amenable to further synthetic elaborations. The observed chiral induction, along with the DFT and XAS analyses, reveals the direct coordination of the chiral phosphine ligand to the iron centre during the carbon-carbon and carbon-metal bond forming step. This new class of iron-catalysed asymmetric reaction will contribute to the synthesis and production of bioactive molecules.

Locking the Dynamic Axial Chirality of Biphenyl Crown Ethers through Threading.

This paper describes the syntheses of [2]rotaxanes comprising 23- and 26-membered biphenyl crown ethers as the macrocyclic components and secondary ammonium ions as the dumbbell-shaped components, and the locking of the dynamic axial chirality of the biphenyl moieties in these structures. Chiral high-performance liquid chromatography (HPLC) revealed that our [2]rotaxane featuring the 26-membered crown ether racemized at room temperature, but the racemization of the [2]rotaxane featuring the 23-membered crown ether did not proceed at room temperature over a period of three days. After separation of the enantiomers of the [2]rotaxane incorporating the 23-membered crown ether through chiral HPLC, we studied its racemization at elevated temperature. The rate of stereoinversion in dimethylsulfoxide (a polar solvent) was faster than that in o-dichlorobenzene (a nonpolar solvent), and herein we discuss these kinetic parameters.

Separation of saccharides using fullerene-bonded silica monolithic columns via π interactions in liquid chromatography.

We report on a potential method to separate sugars by using the specific interaction between fullerenes and saccharides in liquid chromatography (LC). Aromatic rings with high electron density are believed to interact strongly with saccharides due to CH-π and/or OH-π interactions. In this study, the fullerene-bonded columns were used to separate saccharides by LC under aqueous conditions. As a result, 2-aminobenzamide-labeled glucose homopolymer (Glcs) was effectively separated by both C60 and C70 columns in the range of Glc-1 to Glc-20 and high blood glucose level being retained in greater quantity. Furthermore, similar separations were identified by LC-mass spectrometry with non-labeled glucose homopolymers. Theoretical study based on molecular dynamics and DFT calculation demonstrated that a supramolecular complex of saccharide-fullerene was formed through CH-π and/or OH-π interactions, and that the interactions between saccharide and fullerene increase with the increase units of the saccharide. Additionally, the C60 column retained disaccharides containing maltose, trehalose, and sucrose. In this case, it was assumed that the retention rates were determined by the difference of the dipole moment in each saccharide. These results suggest that the dipole-induced dipole interaction was dominant, and that maltose-with the higher dipole moment-was more strongly retained compared to other disaccharides having lower dipole moment.

Competing Roles of Two Kinds of Ligand during Nonclassical Crystallization of Pillared-Layer Metal-Organic Frameworks Elucidated Using Microfluidic Systems.

To diversify metal-organic frameworks (MOFs), multi-component MOFs constructed from more than two kinds of bridging ligand have been actively investigated due to the high degree of design freedom afforded by the combination of multiple ligands. Predicting the synthesis conditions for such MOFs requires an understanding of the crystallization mechanism, which has so far remained elusive. In this context, microflow systems are efficient tools for capturing non-equilibrium states as they facilitate precise and efficient mixing with reaction times that correspond to the distance from the mixing point, thus enabling reliable control of non-equilibrium crystallization processes. Herein, we prepared coordination polymers with pillared-layer structures and observed the intermediates in the syntheses with an in-situ measurement system that combines microflow reaction with UV/Vis and X-ray absorption fine-structure spectroscopies, thereby enabling their rapid nucleation to be monitored. Based on the results, a three-step nonclassical nucleation mechanism involving two kinds of intermediate is proposed.

A Five-layer π-Aromatic Structure Formed through Self-assembly of a Porphyrin Trimer and Two Aromatic Guests.

In this study we synthesized two- and four-armed porphyrins - bearing two carboxyl and four 2-aminoquinolino functionalities, respectively, at their meso positions - as a complementary hydrogen bonding pair for the self-assembly of a D2 -symmetric porphyrin trimer host. Two units of the two-armed porphyrin and one unit of the four-armed porphyrin self-assembled quantitatively into the D2 -symmetric porphyrin trimer, stabilized through ammidinium-carboxylate salt bridge formation, in CH2 Cl2 and CHCl3 . The porphyrin trimer host gradually bound two units of 1,3,5-trinitrobenzene between the pair of porphyrin units, forming a five-layer aromatic structure. At temperatures below -40 °C, the rates of association and dissociation of the complexes were slow on the NMR spectroscopic time scale, allowing the 1 : 1 and 1 : 2 complexes of the trimer host and trinitrobenzene guest(s) to be detected independently when using less than 2 eq of trinitrobenzene. Vis titration experiments revealed the values of K1 (2.1±0.4×105  M-1 ) and K2 (2.2±0.06×104  M-1 ) in CHCl3 at room temperature.

Activator-Promoted Aryl Halide-Dependent Chemoselective Buchwald-Hartwig and Suzuki-Miyaura Type Cross-Coupling Reactions.

Herein, we report the development of aryl halide-dependent chemoselective reactions, viz., the Buchwald-Hartwig type coupling reaction of an aryl iodide with an arylboronic acid and an aryl amine in the presence of a heterogeneous and reusable nickel catalyst and the Suzuki-Miyaura type coupling of an aryl chloride under similar conditions. Control experiments revealed that the presence of stoichiometric amounts of the phenylboronic acid/ester and aryl amine are essential for both reactions. NMR and XAFS studies suggested the formation of a boron-amine "ate" complex.

Amphoteric Homotropic Allosteric Association between a Hexakis-Urea Receptor and Dihydrogen Phosphate.

Conformationally flexible hexakis-urea 1 was synthesized efficiently by condensing hexakis(aminomethyl)benzene with 4-nitrophenyl-(3,5-di-tert-butylphenyl)carbamate. The hexakis-urea 1 is unexpectedly soluble in organic solvents of low polarity due to intramolecular hydrogen bonding. The hexakis-urea 1 recognizes chloride, bromide, and acetate in a 1:2 host-guest ratio and in a positive allosteric manner in CDCl3 . The ability of 1 to recognize dihydrogen phosphate is a unique outcome, and the structure of the associated complex, which contains four dihydrogen phosphate ions, was clarified by single-crystal X-ray structural analysis. However, in solution, a complex with three dihydrogen phosphate ions was identified. The dihydrogen phosphate association in CDCl3 proceeds in an amphoteric allosteric manner; in a positive allosteric manner (K1 K3 ) in the subsequent step.

Controlling the Packing of Metal-Organic Layers by Inclusion of Polymer Guests.

The preparation of metal-organic structures with a controlled degree of disorder is currently one of the most promising fields of materials science. Here, we describe the effect of guest polymer chains on the transformation of a metal-organic framework (MOF). Heating a pillared MOF at a controlled temperature resulted in the exclusive removal of the pillar ligands, while the connectivity of the metal-organic square-grid layers was maintained. In the absence of a polymer, 2D-layers rearranged to form a new crystalline phase. In contrast, the presence of a polymer in the MOF inhibited totally the recrystallization, leading to a turbostratic phase with layers threaded and maintained apart by the polymer chains. This work demonstrates a new synthetic approach toward the preparation of anisotropic metal-organic materials with controlled disorder. It also reveals how guests can dramatically modify the conversion of host MOFs, even though no chemical reaction occurs between them.

Ligand-Free Iron-Catalyzed C-F Amination of Diarylamines: A One-Pot Regioselective Synthesis of Diaryl Dihydrophenazines.

A one-pot synthesis of various 5,10-diaryl-5,10-dihydrophenazines (DADHPs) from diarylamines has been achieved by using an iron-catalyzed C-F amination. Homodimerization of magnesium diarylamides, followed by defluorinative intramolecular cyclization (double ortho C-F amination) in the presence of catalytic FeCl2 and stoichiometric 1,2-dibromoethane, affords the corresponding DADHPs with complete regiocontrol. The unique high reactivity of fluorine over other halogens indicates that amination proceeds via an SNAr mechanism facilitated by iron.