Enzyme‐Inspired Chiral Secondary‐Phosphine‐Oxide Ligand with Dual Noncovalent Interactions for Asymmetric Hydrogenation

Inspired by the unique character of enzymes, we developed novel chiral SPO (secondary‐phosphine‐oxide) ligand (SPO‐Wudaphos) which can enter into both ion pair and H‐bond noncovalent interactions. The novel chiral SPO‐Wudaphos exhibited excellent results in the asymmetric hydrogenation of α‐methylene‐γ‐keto carboxylic acids, affording the chiral γ‐keto acids with up to over 99 % ee . A series of control experiments and DFT calculations were conducted to illustrate the critical roles of both the ion pair and H‐bond noncovalent interactions.     

Step‐Mediated Anisotropic Adsorption and Condensation of tert‐Butylamine on Cu(111)

Scanning tunneling microscopy (STM) combined with density functional theory (DFT) calculations were applied in studying the anisotropic adsorption and condensation of tert‐butylamine (t‐BA) molecules in the vicinity of the steps on the Cu(111) surface. The preferential adsorption at the upper step edges and uneven distribution of t‐BA in the vicinity of the steps illustrate the asymmetric electronic structure of the surface steps. Our observation demonstrates that the adsorption and diffusion of a polar molecule would be significantly mediated by steps on metal surfaces due to the molecule–step interaction and the intermolecular interactions.     

Achieving Strong Positive Cooperativity through Activating Weak Non‐Covalent Interactions

Positive cooperativity achieved through activating weak non‐covalent interactions is common in biological assemblies but is rarely observed in synthetic complexes. Two new molecular tubes have been synthesized and the syn isomer binds DABCO‐based organic cations with high orientational selectivity. Surprisingly, the ternary complex with two hosts and one guest shows a high cooperativity factor (α=580), which is the highest reported for synthetic systems without involving ion‐pairing interactions. The X‐ray single‐crystal structure revealed that the strong positive cooperativity likely originates from eight C?H???O hydrogen bonds between the two head‐to‐head‐arranged syn tube molecules. These relatively weak hydrogen bonds were not observed in the free hosts and only emerged in the complex. Furthermore, this complex was used as a basic motif to construct a robust [2+2] cyclic assembly, thus demonstrating its potential in molecular self‐assembly.     

Synthesis,structural characterization and computational studies of catena‐poly[chlorido[μ3‐(pyridin‐1‐ium‐3‐yl)phosphonato‐κ3O:O′:O′′]zinc(II)]

Coordination polymers are constructed from two basic components, namely metal ions, or metal‐ion clusters, and bridging organic ligands. Their structures may also contain other auxiliary components, such as blocking ligands, counter‐ions and nonbonding guest or template molecules. The choice or design of a suitable linker is essential. The new title zinc(II) coordination polymer, [Zn(C₅H₅NO₃P)Cl]_n , has been hydrothermally synthesized and structurally characterized by single‐crystal X‐ray diffraction and vibrational spectroscopy (FT–IR and FT–Raman). Additionally, computational methods have been applied to derive quantitative information about interactions present in the solid state. The compound crystallizes in the monoclinic space group C 2/c . The four‐coordinated Zn^II cation is in a distorted tetrahedral environment, formed by three phosphonate O atoms from three different (pyridin‐1‐ium‐3‐yl)phosphonate ligands and one chloride anion. The Zn^II ions are extended by phosphonate ligands to generate a ladder chain along the [001] direction. Adjacent ladders are held together via N—H…O hydrogen bonds and offset face‐to‐face π–π stacking interactions, forming a three‐dimensional supramolecular network with channels. As calculated, the interaction energy between the neighbouring ladders is −115.2 kJ mol⁻¹. In turn, the cohesive energy evaluated per asymmetric unit‐equivalent fragment of a polymeric chain in the crystal structure is −205.4 kJ mol⁻¹. This latter value reflects the numerous hydrogen bonds stabilizing the three‐dimensional packing of the coordination chains.     

A simple hydrated salt with a complex hydrogen‐bonding network: tetrakis(5‐amino‐3‐carboxy‐4H‐1,2,4‐triazol‐1‐ium) hexachloridocadmate(II) tetrahydrate

In the title cadmium chloride salt, (C₃H₅N₄O₂)₄[CdCl₆]·4H₂O, the asymmetric unit comprises two N‐protonated 5‐amino‐3‐carboxy‐4H‐1,2,4‐triazol‐1‐ium cations, half a [CdCl₆]⁴⁻ anion and two molecules of water. The Cd²⁺ cation is located on a centre of inversion and is coordinated by six chloride anions, forming a distorted octahedron. In the crystal structure, alternating layers of cations and anions are arranged along the [101] direction, forming a three‐dimensional supramolecular network via a combination of hydrogen‐bonding and aromatic stacking interactions.     

Poly[bis(μ‐4‐benzoyl‐1‐isonicotinoylthiosemicarbazide‐κ2N:S)dichloridocadmium(II)]

The asymmetric unit of the title complex, [CdCl₂(C₁₄H₁₂N₄O₂S)₂]_n, consists of one Cd^II ion located on the crystallographic inversion centre, one 4‐benzoyl‐1‐isonicotinoylthiosemicarbazide ligand and one chloride ligand. The central Cd^II ion adopts a distorted octahedral coordination geometry formed by two pyridyl N atoms of two ligands, two S atoms of two other ligands and two chloride ligands. The thiosemicarbazide ligands act as bridges, linking the metal ions into a two‐dimensional layered structure parallel to the bc plane. Intermolecular N—H...O hydrogen bonds and C—H...π interactions exist between adjacent layers.     

Complexation‐Induced Supramolecular Assembly Drives Metal‐Ion Extraction

Combining experiment with theory reveals the role of self‐assembly and complexation in metal‐ion transfer through the water–oil interface. The coordinating metal salt Eu(NO₃)₃ was extracted from water into oil by a lipophilic neutral amphiphile. Molecular dynamics simulations were coupled to experimental spectroscopic and X‐ray scattering techniques to investigate how local coordination interactions between the metal ion and ligands in the organic phase combine with long‐range interactions to produce spontaneous changes in the solvent microstructure. Extraction of the Eu³⁺–3(NO₃^?) ion pairs involves incorporation of the “hard” metal complex into the core of “soft” aggregates. This seeds the formation of reverse micelles that draw the water and “free” amphiphile into nanoscale hydrophilic domains. The reverse micelles interact through attractive van der Waals interactions and coalesce into rod‐shaped polynuclear Eu^III‐containing aggregates with metal centers bridged by nitrate. These preorganized hydrophilic domains, containing high densities of O‐donor ligands and anions, provide improved Eu^III solvation environments that help drive interfacial transfer, as is reflected by the increasing Eu^III partitioning ratios (oil/aqueous) despite the organic phase approaching saturation. For the first time, this multiscale approach links metal‐ion coordination with nanoscale structure to reveal the free‐energy balance that drives the phase transfer of neutral metal salts.     

Preparation and structural analysis of (±)‐cis‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate and (±)‐trans‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate

Bicycle ring closure on a mixture of (4aS,8aR)‐ and (4aR,8aS)‐ethyl 2‐oxodecahydro‐1,6‐naphthyridine‐6‐carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate, C₁₁H₁₈N₂O₂S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z′ = 2). The reciprocal bicycle ring closure on (3aRS,7aRS)‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate, C₁₀H₁₆N₂O₃, was also accomplished in good overall yield. Here the five‐membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.     

N‐Methyl­pyridinium 3‐cyano‐4‐(di­cyano­methyl­ene)‐5‐oxo‐4,5‐di­hydro‐1H‐pyrrol‐2‐olate

The crystal structure of the title compound, C₆H₈N⁺·C₈HN₄O₂⁻, is characterized by three independent ion pairs (A, B and C) in the asymmetric unit. Each ion pair consists of an anion and a cation, and the three ion pairs have similar geometric parameters. All the anions are arranged as dianion dimers via two N—H⋯O hydrogen bonds and the dimers form one‐dimensional columns parallel to the b axis as a result of π–π interactions. The cations are also stacked, in two different ways: one type of stacking consists of alternating A and B cations, while the other type consists of C cations only. Each dianion dimer stack is surrounded by eight stacks of cations and is not connected directly to other dianion stacks.     

Triaqua(μ‐7‐iodo‐8‐oxidoquinoline‐5‐sulfonato‐κ2N,O8)dioxidouranium(VI) dihydrate

In the title compound, [U(C₉H₄INO₄S)O₂(H₂O)₃]·2H₂O, the asymmetric unit contains a UO₂²⁺ ion coordinated by the N and O atoms of a 7‐iodo‐8‐oxidoquinoline‐5‐sulfonate dianion (ferron anion) and three coordinated water molecules, and two uncoordinated water molecules. The UO₂²⁺ ion exhibits a seven‐coordinate pentagonal bipyramidal geometry. The usual sulfonate oxygen coordination is absent but the sulfonate O atoms, along with the coordinated and lattice water molecules, play a vital role in assembling the three‐dimensional structure via an extensive network of intermolecular O—H...O hydrogen bonds and π–π stacking interactions.     

1‐Carboxymethyl‐3‐methyl‐1H‐imidazol‐3‐ium chloride 2‐(3‐methyl‐1H‐imidazol‐3‐ium‐1‐yl)acetate monohydrate: a crystal stabilized by imidazolium zwitterions

The title compound, C₆H₉N₂O₂⁺·Cl⁻·C₆H₈N₂O₂·H₂O, contains one 2‐(3‐methyl‐1H‐imidazol‐3‐ium‐1‐yl)acetate inner salt molecule, one 1‐carboxymethyl‐3‐methyl‐1H‐imidazol‐3‐ium cation, one chloride ion and one water molecule. In the extended structure, chloride anions and water molecules are linked via O—H...Cl hydrogen bonds, forming an infinite one‐dimensional chain. The chloride anions are also linked by two weak C—H...Cl interactions to neighbouring methylene groups and imidazole rings. Two imidazolium moieties form a homoconjugated cation through a strong and asymmetric O—H...O hydrogen bond of 2.472 (2) Å. The IR spectrum shows a continuous D‐type absorption in the region below 1300 cm⁻¹ and is different to that of 1‐carboxymethyl‐3‐methylimidazolium chloride [Xuan, Wang & Xue (2012). Spectrochim. Acta Part A, 96 , 436–443].     

Hydrogen bonding in 4‐nitrobenzene‐1,2‐diamine and two hydrohalide salts

The structures of 4‐nitrobenzene‐1,2‐diamine [C₆H₇N₃O₂, (I)], 2‐amino‐5‐nitroanilinium chloride [C₆H₈N₃O₂⁺·Cl⁻, (II)] and 2‐amino‐5‐nitroanilinium bromide monohydrate [C₆H₈N₃O₂⁺·Br⁻·H₂O, (III)] are reported and their hydrogen‐bonded structures described. The amine group para to the nitro group in (I) adopts an approximately planar geometry, whereas the meta amine group is decidedly pyramidal. In the hydrogen halide salts (II) and (III), the amine group meta to the nitro group is protonated. Compound (I) displays a pleated‐sheet hydrogen‐bonded two‐dimensional structure with R₂²(14) and R₄⁴(20) rings. The sheets are joined by additional hydrogen bonds, resulting in a three‐dimensional extended structure. Hydrohalide salt (II) has two formula units in the asymmetric unit that are related by a pseudo‐inversion center. The dominant hydrogen‐bonding interactions involve the chloride ion and result in R₄²(8) rings linked to form a ladder‐chain structure. The chains are joined by N—H...Cl and N—H...O hydrogen bonds to form sheets parallel to (010). In hydrated hydrohalide salt (III), bromide ions are hydrogen bonded to amine and ammonium groups to form R₄²(8) rings. The water behaves as a double donor/single acceptor and, along with the bromide anions, forms hydrogen bonds involving the nitro, amine, and ammonium groups. The result is sheets parallel to (001) composed of alternating R₅⁵(15) and R₆⁴(24) rings. Ammonium N—H...Br interactions join the sheets to form a three‐dimensional extended structure. Energy‐minimized structures obtained using DFT and MP2 calculations are consistent with the solid‐state structures. Consistent with (II) and (III), calculations show that protonation of the amine group meta to the nitro group results in a structure that is about 1.5 kJ mol⁻¹ more stable than that obtained by protonation of the para‐amine group. DFT calculations on single molecules and hydrogen‐bonded pairs of molecules based on structural results obtained for (I) and for 3‐nitrobenzene‐1,2‐diamine, (IV) [Betz & Gerber (2011). Acta Cryst. E 67 , o1359] were used to estimate the strength of the N—H...O(nitro) interactions for three observed motifs. The hydrogen‐bonding interaction between the pairs of molecules examined was found to correspond to 20–30 kJ mol⁻¹.     

Interactions of Molecules with cis and trans Double Bonds: A Theoretical Study of cis‐ and trans‐2‐Butene

Noncovalent interactions of cis‐ and trans‐2‐butene, as the smallest model systems of molecules with cis and trans double bonds, were studied to find potential differences in interactions of these molecules. The study was performed using quantum chemical methods including very accurate CCSD(T)/CBS method. We studied parallel and displaced parallel interactions in 2‐butene dimers, in butane dimers, and between 2‐butene and saturated butane. The results show the trend that interactions of 2‐butene with butane are the strongest, followed by interactions in butane dimers, whereas the interaction in 2‐butene dimers are the weakest. The strongest calculated interaction energy is between trans‐2‐butene and butane, with a CCSD(T)/CBS energy of ?2.80 kcal mol^?1. Interactions in cis‐2‐butene dimers are stronger than interactions in trans‐2‐butene dimers. Interestingly, some of the interactions involving 2‐butene are as strong as interactions in a benzene dimer. These insights into interactions of cis‐ and trans‐2‐butene can improve understanding of the properties and processes that involve molecules with cis and trans double bonds, such as fatty acids and polymers.     

Asymmetric Hydroalkoxylation of Non‐Activated Alkenes: Titanium‐Catalyzed Cycloisomerization of Allylphenols at High Temperatures

The asymmetric catalytic addition of alcohols (phenols) to non‐activated alkenes has been realized through the cycloisomerization of 2‐allylphenols to 2‐methyl‐2,3‐dihydrobenzofurans (2‐methylcoumarans). The reaction was catalyzed by a chiral titanium–carboxylate complex at uncommonly high temperatures for asymmetric catalytic reactions. The catalyst was generated by mixing titanium isopropoxide, the chiral ligand (aS)‐1‐(2‐methoxy‐1‐naphthyl)‐2‐naphthoic acid or its derivatives, and a co‐catalytic amount of water in a ratio of 1:1:1 (5 mol % each). This homogeneous thermal catalysis (HOT‐CAT) gave various (S)‐2‐methylcoumarans with yields of up to 90 % and in up to 85 % ee at 240 °C, and in 87 % ee at 220 °C.     

Travelling‐wave ion mobility and negative ion fragmentation of high‐mannose N‐glycans

The isomeric structure of high‐mannose N‐glycans can significantly impact biological recognition events. Here, the utility of travelling‐wave ion mobility mass spectrometry for isomer separation of high‐mannose N‐glycans is investigated. Negative ion fragmentation using collision‐induced dissociation gave more informative spectra than positive ion spectra with mass‐different fragment ions characterizing many of the isomers. Isomer separation by ion mobility in both ionization modes was generally limited, with the arrival time distributions (ATD) often showing little sign of isomers. However, isomers could be partially resolved by plotting extracted fragment ATDs of the diagnostic fragment ions from the negative ion spectra, and the fragmentation spectra of the isomers could be extracted by using ions from limited areas of the ATD peak. In some cases, asymmetric ATDs were observed, but no isomers could be detected by fragmentation. In these cases, it was assumed that conformers or anomers were being separated. Collision cross sections of the isomers in positive and negative fragmentation mode were estimated from travelling‐wave ion mobility mass spectrometry data using dextran glycans as calibrant. More complete collision cross section data were achieved in negative ion mode by utilizing the diagnostic fragment ions. Examples of isomer separations are shown for N‐glycans released from the well‐characterized glycoproteins chicken ovalbumin, porcine thyroglobulin and gp120 from the human immunodeficiency virus. In addition to the cross‐sectional data, details of the negative ion collision‐induced dissociation spectra of all resolved isomers are discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Temperature‐Dependent Prediction of the Liquid Entropy of Ionic Liquids

Modeling of the temperature‐dependent liquid entropy of ionic liquids (ILs) with great accuracy using COSMO‐RS is demonstrated. The minimum structures of eight IL ion pairs are investigated and the entropy, calculated from ion pairs, is found to differ on average only 2 % from the available experimental values (119 data points). For calculations with single ions, the average error amounts to 2.6 % and stronger‐coordinating ions tend to give higher deviations. Additionally, the first parameterization of the standard liquid entropy for ILs is presented in the context of traditional volume‐based thermodynamics (S_l⁰=1.585 kJ mol^?1 K^?1 nm^?3?r_m³+14.09 J mol^?1 K^?1), which sheds light on the statistical treatment of ionic interactions. The findings provide the first direct access to accurate predictions of liquid entropies of ILs, which are tedious and time‐consuming to measure.     

New Polymer‐Supported Mono‐ and Bis‐Cinchona Alkaloid Derivatives: Synthesis and Use in Asymmetric Organocatalyzed Reactions

The straightforward synthesis of polystyrene‐supported Chinchona alkaloids and their application in the asymmetric dimerization of ketenes is reported. Six different immobilized derivatives, consisting of three dimeric and two monomeric 9‐O ethers, were prepared by “click” anchoring of soluble alkaloid precursors on to azidomethyl resins. The resulting insoluble polymer‐bound (IPB) organocatalysts were employed for promoting the dimerization of in‐situ generated ketenes. After opening of the ketene dimer intermediates with N,O‐dimethylhydroxylamine, valuable Weinreb amides were eventually obtained in good yield (up to 81 %) and excellent enantiomeric purity (up to 96 % ee). All of the IPB catalysts could be recycled effectively without significant loss of activity and enantioselectivity. The extension to other asymmetric transformations (meso‐anhydride desymmetrization and α‐amination of 2‐oxindoles) is also briefly discussed.     

Amine‐Urea‐Mediated Asymmetric Cycloadditions between Nitrile Oxides and o‐Hydroxystyrenes by Dual Activation

The first example of asymmetric 1,3‐dipolar cycloadditions between nitrile oxides and o ‐hydroxystyrenes, mediated by cinchona‐alkaloid‐based amine‐ureas is reported. The method is based on a dual activation involving both LUMO and HOMO activations. In addition to the stoichiometric asymmetric induction, a catalytic amount of amine‐urea enables the cycloadditions to proceed in an enantioselective manner. Computational studies strongly support the HOMO activation of o ‐hydroxystyrenes and LUMO activation of nitrile oxides by hydrogen‐bonding interactions with the Brønsted acid/base bifunctional catalyst.     

Anion‐π Catalysis: Focus on Nonadjacent Stereocenters

Anion‐π interactions have been recently introduced to catalysis with the idea to stabilize anionic intermediates on π‐acidic surfaces. Realized examples include enolate, enamine and iminium chemistry, domino processes and Diels–Alder reactions. Moving on from the formation of contiguous stereogenic centers on π‐acidic surfaces, herein we report the first asymmetric anion‐π catalysis of cascade reactions that afford nonadjacent stereocenters. Conjugate addition‐protonation of achiral disubstituted enolate donors to 2‐chloroacrylonitrile generates 1,3‐nonadjacent stereocenters with moderate enantioselectivity and diastereoselectivity. The explored catalysts operate with complementary naphthalenediimide and fullerene surfaces with highly positive quadrupole moments and high polarizability, respectively, and proximal amine bases. We find that anion‐π catalysts can increase the diastereoselectivity of the reaction beyond the maximal 1:4.0 dr with conventional catalysts to maximal 5.3:1 dr on the large fullerene surfaces. The enantioselectivity of anion‐π catalysts, best on the confined naphthalenediimide surfaces with strong quadrupole moment, exceed the performance of conventional catalysts except for comparable results with a new, most compact, surprisingly powerful bifunctional control catalyst. Simultaneously increased rates and stereoselectivities compared to control catalysts without π‐acidic surface support that contributions of anion‐π interactions to the catalytic cascade process are significant.     

Origins of the Enantio‐ and N/O Selectivity in the Primary‐Amine‐Catalyzed Hydroxyamination of 1,3‐Dicarbonyl Compounds with In‐Situ‐Formed Nitrosocarbonyl Compounds: A Theoretical Study

Chemoselective control over N/O selectivity is an intriguing issue in nitroso chemistry. Recently, we reported an unprecedented asymmetric α‐amination reaction of β‐ketocarbonyl compounds that proceeded through the catalytic coupling of enamine carbonyl groups with in‐situ‐generated carbonyl nitroso moieties. This process was facilitated by a simple chiral primary and tertiary diamine that was derived from tert‐leucine. This reaction featured high chemoselectivity and excellent enantioselectivity for a broad range of substrates. Herein, a computational study was performed to elucidate the origins of the enantioselectivity and N/O regioselectivity. We found that a bidentate hydrogen‐bonding interaction between the tertiary N⁺? H and nitrosocarbonyl groups accounted for the high N selectivity, whilst the enantioselectivity was determined by Si‐facial attack on the (E)‐ and (Z)‐enamines in a Curtin–Hammett‐type manner. The bidentate hydrogen‐bonding interaction with the nitrosocarbonyl moieties reinforced the facial selectivity in this process.