Angewandte Chemie International Edition

The liquid-phase preparation of copper, either as freestanding submicrometer-thin foil or supported on a substrate, is presented by M. Niederberger et al. in their Communication on page 4743 ff. A solution of copper acetylacetonate initially forms a mirror on the reaction container wall, which then delaminates. When the copper is supported on a flexible substrate, such as Kapton, it can be structured into conduction line patterns.

Inspired from natural nacre a transparent, layered nanocomposite hydrogel was fabricated from poly(N-isopropylacrylamide) and clay. This hydrogel shows excellent mechanical properties and a hierarchical microstructure. In their Communication on page 4676 ff., Q. Cheng et al. introduce a concept for the preparation of wet-chemical high-performance materials that can be used for applications, such as tissue-engineering, sensors, artificial muscles, and underwater antifouling materials.

Like most journals and newspapers worldwideAngewandte Chemie International Edition is printed with Pigment Red 57:1. M. U. Schmidt et al. report in their Communication on page 4735 ff. that the actual shade of red depends on the hydration state and thus may change with the weather conditions. The crystal structures of the pigment in various hydration states have been solved by X-ray powder diffraction.

A blood sample was broken up into nanoliter volumes, and subsequently each aliquot was ranked based on whether or not a rare cell was present in the ensemble of cells within the aliquot. This approach is called ensemble decision aliquot ranking (eDAR). In their Communication on page 4618 ff., D. T. Chiu et al. show that the eDAR technique is well-suited for the enrichment of rare cells, such as circulating tumor cells.

“What I appreciate most about my friends is loyalty and frankness. The greatest scientific advance of the last decade was published at the very beginning of the 21st century: the first draft sequence and analysis of the human genome …” This and more about Max Malacria can be found on page 4518.

Oxford University Press, New York, 2011. 208 pp., hardcover, $ 24.95.—ISBN 978-0199737697

Cations for all seasons: Silylium cations, because of their high Lewis acidity, are suitable for catalysis like almost no other class of reactive cations. Starting from a new, elegant synthetic route to triarylsilylium ions and their application in hydrogen activation, the general potential of silylium ions in synthesis is discussed.

The fixation with fixation: Microorganisms have converted atmospheric nitrogen into ammonia for millions of years under ambient conditions, whereas the Haber–Bosch process requires high pressures and temperatures. Some recent studies on the biological and synthetic generation of ammonia should contribute to a better understanding of the mechanism of this reaction, which remains one of the most challenging goals for catalysis.

Chiral anions can do it: Asymmetric phase-transfer catalysis is no longer limited to cationic catalysts. Lipophilic BINOL phosphate anions are superior catalysts for the asymmetric electrophilic fluorination of alkenes under phase-transfer conditions (see picture). Now complex fluorinated compounds can be synthesized selectively from simple alkene starting materials.

Recently completed total syntheses and the ingenious synthetic approaches developed for the construction of the biologically significant polycyclic polyprenylated acylphloroglucinols (PPAPs) are presented in this Review. The state-of-the-art synthetic methods and strategies, current limitations, as well as the outlook for this field are highlighted.

X marks the spot! A fascinating packing motif is observed in a novel cruciform oligothiophene containing a Ge (violet; see picture) spiro center. Long-range interchain interactions between molecules and strong electronic coherence between orthogonal chains within the molecules are present. Such ordering is advantageous for bulk charge transport, as demonstrated by high short-circuit currents in bulk heterojunction organic solar cells.

Unrestricted: Pseudoephenamine is introduced as a versatile chiral auxiliary and an alternative to pseudoephedrine in asymmetric synthesis. It is free from regulatory restrictions and leads to remarkable stereocontrol in alkylation reactions, especially in those that form quaternary carbon centers. Amides derived from pseudoephenamine exhibit a high propensity to be crystalline substances, and provide sharp, well-defined signals in NMR spectra.

Building cycles: A strategy for the concise, stereoselective synthesis of aspidosperma alkaloids and related structures via a common putative diiminium ion intermediate is reported. The approach enables the dimerization of aspidosperma-type structures at the sterically hindered C2 position. The intermediate is prepared in one step from the shown lactam through an electrophilic double-cyclization cascade (see scheme; Tf=trifluoromethanesulfonyl).

CF₃on C: Trifluoromethylation of allylsilane derivatives was accomplished through the use of CuI and Togni's reagent (1) under mild conditions. The reaction of allylsilanes without a substituent in the 2-position gave vinylsilane derivatives, while 2-substituted allylsilanes afforded desilylated products. The utility of the products was demonstrated through their further transformation.

Enantioselective mono-fluorination of α-keto esters was achieved using a mildly basic palladium μ-hydroxo complex as catalyst. Subsequent one-pot reduction afforded optically active β-fluoro-α-hydroxy esters. These compounds were then converted into β-fluoro-α-amino esters, which are potentially useful in medicinal chemistry research.

Stay flexible: Rigid preorganization is not always the best approach to molecular recognition. Unlike previous synthetic lectins, new receptors (see picture) were synthesized that possess conformational freedom which allows hydrophobically driven collapse of the cavity. Nonetheless, they bind their carbohydrate targets in water with ground-breaking affinities (up to 4500 M⁻¹ for methyl cellobioside, R=Me) and selectivities.

Rearranged: The attachment of gas-phase divalent metal ions that bind as strongly as Mg²⁺ and transition-metal ions to the dipeptide PhePhe results in displacement of the amide proton by the newly characterized iminol tautomerization rearrangment. More weakly coordinating ions bind in the known charge-solvation mode. Infrared multiple-photon dissociation spectroscopy using the free-electron laser clearly shows the tautomeric transition.

Building bowls: An effective intramolecular aryl–aryl coupling is the key step in rational fullerene synthesis and in synthesis of extended buckybowl structures. Such a process can be embodied very efficiently through quantitative HF elimination on active Al₂O₃. The process is characterized by an unprecedentedly high chemoselectivity and regiospecificity.

Core–shell nanostructures of a photoluminescent Eu-containing polyoxometalate (Eu-POM) with double-hydrophilic neutral–cationic block copolymer PEO₁₁₄-b-PDMAEMA₁₆ in aqueous solution were fabricated by self-assembly driven by electrostatic interactions (see scheme; neutral block blue, cationic block red). The emission of Eu-POM, which depends on the charge ratio of the Eu-POM/copolymer system, is enhanced up to 20-fold by complexation with the cationic PDMAEMA block.

The best of both worlds: BODIPY-based imaging probes can be tracelessly transformed into hybrid PET/fluorescence imaging reagents by direct ¹⁹F/¹⁸F exchange without the need for redesign. This approach has the potential to accelerate not only the development of imaging agents, but perhaps also the screening of therapeutic molecules.

Right on target: A multifunctional nanoprobe is designed for target-cell-specific imaging and in situ detection of intracellular miRNA. The nanoprobe is prepared by functionalizing SnO₂ nanoparticles with both folic acid (FA), a target-cell-specific moiety to recognize folate receptors overexpressed on cancer cells, and a gene probe to inhibit or recognize intracellular miRNA levels (see scheme).

Transmembrane transport: A combination of photon and fluorescence correlation spectroscopies is used to study the internalization of nanoparticles into a minimal model system based on poly(dimethylsiloxane)-block-poly(2-methyloxazoline) vesicles (see picture). These techniques provide information about the kinetics and dynamics of this transport process in real time.

Enrichment of cells: An approach called ensemble-decision aliquot ranking (eDAR) for isolating rare cells from peripheral blood is described. The eDAR process has a recovery of over 93 % (number of runs n=9) with a zero false positive rate (n=8) and provides direct easy access to individual isolated live cells for downstream single-cell manipulation and analysis (CTCs=circulating tumor cells).

Potential control: A Ru^II-bound pterin forms a stable hydrogen-bonding adduct with a guanine derivative through three-point recognition. A large positive shift of the reduction potential of the pterin ligand up to +320 mV is observed (see picture). For the thymine derivative, the mode of hydrogen bonding is altered. Regulation of redox potentials of a pterin coenzyme by noncovalent interaction is demonstrated.

Gene Genie: RNA-mediated gene assembly is possible in a single day from oligonucleotide sequences on a DNA array. A T7 promoter is appended to each surface-bound oligonucleotide and many RNA copies of each are then produced with T7 RNA polymerase (see Figure). These RNA molecules self-assemble into the desired full-length transcript by hybridization and ligation, which is then converted into double-stranded DNA by reverse transcriptase polymerase chain reaction.

Playing it cool: Almost all of the constituent parts of the complex [Ln^III₄M^II₈(OH)₈(L)₈(O₂CR)₈]X₄, namely the lanthanide ions Ln³⁺, the transition-metal ions M²⁺, the bridging ligand L, the carboxylates, and the counterions X can be exchanged, thus allowing a thorough understanding of the individual contributions to the magnetocaloric effect. Example in picture: Gd purple, Cu green, O red, N blue.

The concept of drug-likeness distills the physicochemical properties of small-molecule drugs to a set of rules. Macrocyclic drugs are known to break these rules. A structure-based macrocyclization strategy was applied to design new hepatitis C virus NS5B inhibitors with improved pharmacokinetic properties, exemplifying a rational strategy for overcoming the confines of standard “drug-like chemical space”.

A matter of size: The particle size effect on the activity of the oxygen reduction reaction of size-selected platinum clusters was studied. The ORR activity decreased with decreasing Pt nanoparticle size, corresponding to a decrease in the fraction of terraces on the surfaces of the Pt nanoparticles (j_k=kinetic current density, see picture).

Bending over backwards: A highly aligned carbon nanotube sheet orients crosslinked liquid-crystalline polymer through a simple melting process (see picture). The resulting composite film can be rapidly bent and unbent by alternate irradiation with UV and visible light. The film also exhibits excellent mechanical and electrical properties due to the incorporation of aligned CNTs.

Got a light? An efficient method for the synthesis of phosphorus-functionalized bis(acyl)phosphaneoxides (BAPOs) was developed, which allows the preparation of photoactive polymers or grafting of these photoinitiators to various surfaces. Irradiation in the presence of polymerizable monomers leads to coatings that can be deposited imagewise.

Lipodisq particles are polymer–lipid complexes formed by detergent-free methods. Lipodisq particles containing dimyristoylphosphatidylcholine (DMPC) are characterized by increased lipid ordering compared to a DMPC dispersion. The styrene and maleic acid groups of the polymer interact with the DMPC lipid chains in bilayers, as well as lipid headgroups in the Lipodisq periphery (see picture).

Insensitivity: A series of molecules containing a common head group and body as well as structurally varied tail groups (-R) has been used in junctions with the structure Ag/S(CH₂)₄CONH(CH₂)₂R//Ga₂O₃/EGaIn to study the rates of charge transport by tunneling. Changing the structure of R over a range of common aliphatic, aromatic, and heteroaromatic organic groups was found to not significantly influence the rate of tunneling (see plots; the dashed lines represent calibration standards).

Acid assists: The reaction of [{WO(O₂)₂}₂(μ-O)]²⁻ with 0.5 equivalents of HNO₃ gave a tetranuclear peroxotungstate (1; see picture) that has a dramatically enhanced activity for the epoxidation of cyclooctene with H₂O₂ compared to various peroxotungstates. The 1-catalyzed system was applicable to the selective oxidation of various kinds of substrates with 1.0–1.5 equivalents of H₂O₂.

No pressure: The oxidation of aromatic CH bonds at room temperature was realized through a copper-catalyzed “oxygenase-type” oxidation of arenes and heteroarenes in the presence of air (see scheme). The reaction involves an oxygen-atom transfer from O₂ in the air onto the substrates.

SiH bonds can be activated by organozinc and silylzinc compounds in the presence of minute amounts of radical initiators such as tBu₂Hg or AIBN, yielding zinciosilanes in good yields (see scheme). Activation of dihydridosilanes leads to geminal dizinciosilanes. Zincio-bridged disilyllithium compounds, which have three (1) and four metal–silicon bonds, were also synthesized.

Inspired by nacre, a layered poly(N-isopropylacrylamide)–clay nanocomposite hydrogel was successfully fabricated by combination of vacuum-filtration self-assembly and photo-initiated in situ polymerization. This bio-inspired layered nanocomposite hydrogel shows excellent mechanical properties, which can rival some biological soft tissues (see picture).

Furans of gold: The first example of a gold-catalyzed intermolecular addition of carbon ylides to terminal alkynes is reported (see scheme; DCE=dichloroethane, Tf=trifluoromethanesulfonyl). Subsequent intramolecular trapping of the generated gold carbene completes a formal [3+2] cycloaddition, which represents a novel synthesis of 2,4-disubstituted furans.

Pass the P: Catalytic direct aldol addition of α-hydroxy trialkyl phosphonacetates to aldehydes affords α-hydroxy-β-phosphonyloxy ester products (see scheme). The fully substituted glycolate enolate intermediate is generated in situ under mild conditions by a [1,2] phosphonate–phosphate rearrangement. High enantioselectivity and dramatic enhancement of reaction diastereocontrol is realized by the application of chiral iminophosphorane catalysts.

A platinum star performance: Quasi-single-crystalline Pt nanoparticles with peculiar morphologies—cubic dendrites, planar tripods, and fivefold stars—were synthesized in high yield. Shape selectivity was achieved by finely tuning the growth kinetics under a dihydrogen atmosphere.

Going retro: The diazabicycloundecane-induced retro-Claisen rearrangement of a linear precursor serves as the key step to form the hindered ester of the polypropionate dolabriferol (1, see scheme, PMB=p-methoxybenzyl, PMP=p-methoxyphenyl, TES=triethylsilyl). The rearrangement is thought to mimic the biosynthetic formation of 1.

Direct alkenylation of the C2-position of indoles bearing an easily removable N-pyrimidyl group with alkynes has been achieved by using a cobalt catalyst complexed with a phosphine–pyridine bidentate ligand. This reaction has wide substrate scope and is highly efficient and stereoselective at room temperature. The alkenylated indoles serve as useful platforms for further synthetic transformations (some products of these transformations are shown in the scheme).

Breaking down methane: A Ga³⁺-modified microporous titanosilicate (ETS-10) exhibits distinct photoactivity for the cleavage of the methane CH bond at room temperature. The highly enhanced activity is attributed to the synergistic effect of gallium-induced CH bond polarization and a titania-based photoredox process.

Restructuring: An unprecedented framework structure made up of tetrahedra has been discovered in a novel high-pressure polymorph of the phosphorus oxonitride PON by treating a single-source precursor at 12 GPa and 1250 °C. It is the first polymorph of PON that does not crystallize in a structure type known from SiO₂.

The incredible bulk: The first palladium-catalyzed amidation of five-membered heterocyclic bromides with multiple heteroatoms was achieved using the Pd/1 catalyst system. N-Arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes were synthesized in moderate to excellent yield. Experimental results and DFT calculations point to the need for an electron-rich and sterically demanding biaryl phosphine ligand to promote these difficult reactions.

CO₂snapper: Compounds containing both acidic and basic P,N functionalities have been prepared. Of these, two amidophosphoranes containing highly reactive PN bonds within four-membered rings react rapidly with CO₂, resulting in relief of ring strain. These compounds demonstrate the utility of phosphorus as a Lewis acid for small-molecule activation.

Small is beautiful: spectroscopic proof or any other indication for the existence of formyl azide (HC(O)N₃) has until now been lacking. Although it liberates dinitrogen much more rapidly than homologous acyl azides, it has been prepared for the first time by four different methods (see scheme).

Ménage à trois: In a three-component reaction, furancarbaldehydes 1, anilines 2, and the monocyclopropanated pyrrole 3 can be assembled highly stereoselectively to give cis-4,5-disubstituted pyrrolidinones (see scheme; Boc=tert-butoxycarbonyl). The products are lead structures for pharmaceutically important compounds.

It's all in the CAN: Cerium ammonium nitrate (CAN) promotes the oxidative radical cyclization of furan β-ketoesters to form macrocycles of varying ring sizes. The reaction is tolerant of unsaturation, oxygenation, and nitrogen and oxygen heterocycles in the carbon backbone tether.

Chemistry at defects: The concentration of defect sites at rutile TiO₂ (r-TiO₂) surfaces of both single crystals and powder particles was determined by UHV-FTIR spectroscopy using CO as a probe molecule (see picture). The potential of this novel approach is demonstrated by unraveling the mechanism of reductive coupling of formaldehyde to give ethylene.

The Red carrying the news around the world: Most newspapers and journals worldwide (including Angewandte Chemie) are printed with Pigment Red 57:1. The crystal structures of this pigment in various hydration states have now been determined by X-ray powder diffraction.

A slow electron waltz: Catalysis in single-electron steps with radicals as intermediates is essential for an atom-economical arylation of epoxides with a proton-coupled electron transfer as a key step. Stabilization of the catalyst is essential for low catalyst loading, as demonstrated by reaction-progress kinetic analysis, cyclic voltammetry, and calculations.

Metal foils: A simple electroless liquid-phase deposition technique gives access to freestanding copper foils and supported copper thin films. The films can be easily structured into conducting line patterns for electronics applications (see picture).

A knot that ties itself! The entanglement of six ligands coordinated to three Pd^II ions results in the quantitative formation of a walnut-shaped supramolecular cage. Each of the two hemispheres resembles a trefoil knot. The solution-state structure was elucidated using a combination of NMR experiments and calculated model structures. The final structure was selected from several models by topological analyses and encapsulation of chiral camphorsulfonate ions.