Angewandte Chemie International Edition

Ultrafast electron microscopy …… has been used to view the reversible expansion and contraction of a single crystal of [Cu(TCNQ)] (see film strip; TCNQ=7,7,8,8-tetracyanoquinodimethane), induced with near-infrared laser pulses, as well as the photoinduced reduction of copper ions to form discrete metal clusters (see picture, top right), as described by A. H. Zewail et al. in their Communication on Page 9206 ff. The crystal expands along the π-stacking axis of the TCNQ molecules upon exposure to light, but rapidly returns to its original state in the absence of laser light.

Application in veterinary medicine was proposed for the sesquiterpenoids pasteurestins A and B because of their strong and selective activity against Pasteurella haemolytica. A Vollhardt [2+2+2] cycloaddition was the key step in their total synthesis, which is described by J. Mulzer et al. on page 9320 ff., and subsequently their absolute and relative configurations could be established and their biological activities more precisely specified. Another feature of the synthesis of pasteurestin B is a tin(II) enolate mediated Reformatsky-type condensation.

Back to copper: The Rh-catalyzed reactions of diazocarbonyl compounds with amines, leading to NH insertion products, have found wide application. However, an enantioselective variant has remained elusive. A return to copper catalysis, first reported for carbene NH insertions over 50 years ago, in the presence of chiral ligands and a large noncoordinating counterion, has resulted in enantioselective NH insertion into anilines.

The 103-year-old reaction of N-(2,4-dinitrophenyl)pyridinium chloride with primary amines was rediscovered by two research groups recently. Since neither authors nor referees knew the pertinent literature, the products were assigned the structure of the diaza[12]annulenes 1, although they are nothing but N-substituted pyridinium salts.

The dramatic societal upheavals and radical value shifts that occurred during the first half of the 20th century influenced every aspect of life, including the scientific and research systems. A biography of Heinrich Wieland, awarded the Nobel Prize for Chemistry in 1927, one embedded in a chronicle of the times, shows clearly how this one individual adapted to multiple drastic changes in his environment.

Sought for weak coordination: The first synthesis of the [B(CF₃)₄]⁻ ion by fluorination of the [B(CN)₄]⁻ ion marks the beginning of a new development in the field of B-CF₃ chemistry. In concentrated sulfuric acid one of the CF₃ groups is transformed into a CO ligand. The borane carbonyl (CF₃)₃BCO is a reactive species and excellent starting material for the synthesis of various (CF₃)₃B compounds, for example, the pnicogeneethynyl complexes [(CF₃)₃BCPnic]⁻ (Pnic=N, P, As).

Tri-, bi-, and monoradicals: The reactivity of a σ,σ,σ-triradical, 2,4,6-tridehydropyridinium cation, was compared with that of related mono- and biradicals in a Fourier transform ion cyclotron resonance mass spectrometer. The triradical has a doublet ground state and contains three interacting radical sites. The reactivity of the triradical more closely resembles that of related monoradicals than related biradicals.

Give me five! An organocatalyzed two-component domino reaction has been developed in which two new CC bonds and five stereocenters are created in a one-pot fashion (see scheme; DABCO=1,4-diazabicyclo[2.2.2]octane, TMS=trimethylsilyl). The striking features of this transformation are the high preference for one diastereomer (out of 32 possible isomers) and enantioselectivities of up to 94 %.

On again, off again: The reversible expansion and contraction of single crystals of [Cu(TCNQ)] induced by near-infrared laser pulses was studied with ultrafast electron microscopy (TCNQ=7,7,8,8-tetracyanoquinodimethane). The crystal expands along the π-stacking axis of the TCNQ molecules, but not perpendicular to this axis, when exposed to light. The crystal returned to its original structure when the laser light was blocked.

Take a closer look! The first enantioselective total synthesis, stereochemical reassignment, and absolute configuration of the metabolite neopeltolide is described (see picture). Synthetic highlights of this route include a modified Evans–Tishchenko reduction to introduce the C11 stereocenter, [4+2] annulation to construct the pyran system, and a Still–Gennari olefination to install the oxazole side chain.

Breaking up the crowd: The pathological aggregation of tau protein correlates closely with the progression of Alzheimer's disease. Rhodanine-based inhibitors of tau aggregation (e.g. 1) have been identified, and it has been shown that tau aggregation in a cell model is reversible and can be inhibited by small molecules at nanomolar concentrations (see SEM images).

Dotting the i: The i-motif is a four-stranded DNA structure that consists of intercalated hemiprotonated C:C⁺ base pairs. Although they contain 2′-ribo oxygen atoms, LNA-modified TC₅ oligonucleotides are also able to form stable tetrameric i-motif structures at low pH values (see view into one of the two narrow grooves of such a structure), as shown by a combination of CD, UV, and NMR spectroscopy.

In anaerobic organisms such as E. coli the tyrosine lyase ThiH is essential for the biosynthesis of the thiazole moiety of the vitamin thiamine. ThiH is a member of the “radical AdoMet” family. The products formed by cleavage of tyrosine in vitro have been identified and suggest a radical-mediated cleavage resulting in p-cresol and dehydroglycine which is hydrolyzed to glyoxylate.

Getting a reaction: A condensation reaction occurs between a dialdehyde and an amine coadsorbed on a Au(111) surface in an ultrahigh vacuum. The self-assembled structures formed by the diimine reaction product on the surface have been investigated by scanning tunneling microscopy (see image). A solvent-free reaction path is proposed from DFT calculations.

Radicalized aldols: Enones with a fixed s-cis geometry can undergo enantioselective radical reactions. The synthesis of aldol products derived from cyclic ketones in excellent yields and enantioselectivity demonstrates that s-cis-enones are excellent substrates for radical reactions. A tentative model to explain the stereochemical outcome of the reaction consists of nucleophilic radical addition to the si face (see picture).

In the nanosphere: The cooperative self-assembly of CdSe/ZnS nanoparticles and an amphiphilic block copolymer leads to unique spherical assemblies. In these assemblies, the nanoparticles (green circles) are located at the interface between an outer polymer shell and an inner polymer core (see picture).

A two-ring binder: To facilitate the design of metalloproteins, the bidentate, metal-binding amino acid bipyridylalanine (BpyAla) was genetically encoded in E. coli in response to the amber nonsense codon with high fidelity and yield. The incorporation of BpyAla requires a BpyAla-specific aminoacyl-tRNA synthetase, which was evolved in a stepwise fashion. The structural basis of selective recognition of BpyAla by this synthetase was also determined.

No (self-)assembly required: Both spherical and anisotropic “dumbbell” polymer nanoparticles with targeted shapes in the <100-nm size range were prepared by direct synthesis not relying on self-assembly. Atom-transfer polymerization techniques at high concentrations produce both spherical and dumbbell-like nanoparticles directly from simple vinyl monomers on a multigram scale.

Being specific: The specific conversion of Cys (seleno-Cys) into Ala by a free-radical-mediated reduction can be achieved in an aqueous medium under mild conditions (see scheme, PG=protecting group). The conversion can be achieved in the presence of all 20 natural amino acids as well as a range of functional groups. This native chemical ligation followed by the Cys into Ala conversion will enable the synthesis of complex peptides and glycopeptides.

Electronic and structural dynamics of an industrially relevant Pt/CeO₂–ZrO₂ catalyst with an ordered arrangement of Ce and Zr ions during oxygen storage/release processes at 573–773 K were studied in real time by time-resolved energy-dispersive XAFS at the Zr K edge and Ce L₃ edge (see experimental setup). On the basis of these results, the roles of Ce and Zr ions in the function of the mixed-oxide catalyst were elucidated.

The best of both worlds: With a coordinating 2-pyridylsulfonyl group as the N-activating group, aromatic aldimines show unprecedented high reactivity towards the direct addition of alkyl zinc bromide reagents in the presence of catalytic amounts of Cu(OTf)₂. The reaction combines high reactivity with wide functional-group compatibility to provide ready access to functionalized benzylamines and derivatives (see example). Tf=trifluoromethanesulfonyl.

One by one or two by two: In a general approach to the iterative construction of oligopyrroles, the cycloaddition of azomethine ylides derived from pyrrolyl α-iminoesters with 1,2-bis(phenylsulfonyl)ethylene is followed by the elimination of the sulfonyl groups in situ under basic conditions. This strategy is amenable to the introduction of one or two pyrrole units in each iterative cycle.

Eureka! The first conquest of the exceptionally potent cytotoxic agent amphidinolide H, which exhibits activity in the picomolar range against human epidermoid cancer cells, was long overdue. The successful route critically hinges upon the scrupulous optimization of the fragment-coupling events (see picture; RCM=ring-closing metathesis) and on the careful adjustment of the peripheral protecting-group pattern.

Layered chips: The experimental proof of concept of the combination of resonant microelectromechanical systems with molecularly imprinted polymers (MIPs) has been shown for the first time. The use of micromembrane gravimetric sensors carrying piezoelectric thin films, the surfaces of which are coated with MIPs by using a cantilever-based deposition tool (see image), is reported. The multiplexed format of the chips shows the potential of the system for the specific, label-free, reliable detection of target molecules.

Converging on the target: The highly cytotoxic F-ATPase inhibitor cruentaren A constitutes an interesting lead in the quest for innovative chemotherapeutic agents for the treatment of various diseases, including cancer. Its synthesis was achieved in an overall yield of 3 % by an expeditious convergent route involving a ring-closing alkyne metathesis reaction (RCAM) for the formation of the macrocyclic ring (see picture).

Shapes from water: Pd nanocrystals with controllable shapes are synthesized by reducing a Pd salt with citric acid in aqueous solution. Citric acid favors the formation of octahedra, icosahedra, or decahedra (see picture) owing to its strong binding to the {111} facets of Pd. Shape control of these nanocrystals is readily accomplished by adjusting the amounts of Na₂PdCl₄ precursor and citric acid added to the reaction mixture.

Hyperextension: A hydrogen-bonded, dimeric capsule can be expanded with four, eight, or twelve glycoluril spacers (see picture) that increase the cavity's volume by up to 530 ų and its length by up to 21 Å. The extended assemblies are chiral and encapsulate a variety of normal alkanes. The expanded capsules suggest that increasingly complex capsules may emerge from other spacers with hydrogen-bonding capabilities and curved surfaces.

Chiral assemblies of achiral molecules: High-resolution STM images of zwitterionic organic dipoles deposited on Si(111)-7×7 show a chiral molecular assembly on this surface (see picture). Density functional calculations demonstrate that a sulfonato group can act as an electrostatic shield that protects the π skeleton of organic molecules from the dangling bonds of semiconductor surfaces, which is a major advance in the deposition of π-conjugated molecules.

Freedom of choice: Both enantiomers of free homoallylic amines with two stereogenic centers (including a quaternary center) can be prepared at will from vinyl copper intermediates derived from either a vinyl iodide or an alkyne (see examples; the sulfinyl group is cleaved readily under mild acidic conditions). In this one-pot strategy, zinc homologation of the vinyl copper species is followed by treatment with a sulfinylimine derivative.

Working together: Synergy between Michael addition and S_N2′ displacement allows stabilized carbanions or the nucleophilic carbon atoms of enamines to undergo intramolecular addition to an α,β-unsaturated ester unit bearing an allylic leaving group to generate unsaturated carbocycles (see scheme). The starting esters are available by a selenium-based alternative to the classical Baylis–Hillman reaction, and complex structures can be assembled.

Thioesters need not apply: Cryptophycin thioesterase (Crp TE) cleaves and macrolactonizes linear cryptophycin substrates bound to activated safety-catch PEGA resin. This novel enzymatic solid-phase approach was used to further investigate the tolerance of Crp TE for structural variations of substrates.

The -enes have it! A resident alkene directs a nickel-catalyzed cross-coupling of cyclic anhydrides with diorganozinc reagents. Relative directing effects parallel the stability of nickel–alkene complexes, with less-hindered terminal olefins dominating over internal olefins.

Bound to be better: The formation of a strong complex between the chromophoric dye malachite green (MG, in green) and the G-quadruplex structure (represented in black) of the guanine-rich single-strand oligomer sequence d(G₂T)₁₃G results in a 100-fold enhancement of the fluorescence yield of MG. The existence of an intra- or interstrand G-quadruplex structure depends on the oligomer concentration and the ionic strength of the solution.

High, but not dry: A highly enantioselective Michael reaction in water has been developed by using a simple DNA-based catalyst. Enantioselectivities of up to 99 % ee could be obtained by using nitromethane and dimethyl malonate as the nucleophiles and α,β-unsaturated 2-acylimidazoles as the Michael acceptors. The reactions can be performed on a preparative scale and the catalyst can be recycled.

Fooling nature: The replacement of amide and alkene groups in a biological setting with the 1,2,3-triazole group led to the discovery of compounds with a unique vanilloid/cannabinoid mixed profile. For example, the natural amides (see picture, above) and their triazole mimics (below) exhibit similar agonistic (X=H) or antagonistic (X=I) activity towards the TRPV1 receptor; however, only the triazole derivatives also show cannabinomimetic activity.

100 years after the prediction of the existence of C₂O₃ by Berthelot, doubly charged C₂O₃²⁺ has been identified as a product in the reaction of CO₂²⁺ with CO₂ (see scheme). The occurrence of this reaction for such a small dication indicates that bond-forming processes might play a much larger role in reactions of dications than has been anticipated to date.

Fresh pasture for the [2+2+2] cycloaddition: The two sesquiterpenoids pasteurestin A and B, which exhibit strong and selective antibacterial activity against Pasteurella haemolytica, have been prepared in a synthesis relying on a [2+2+2] Vollhardt enediyne cycloaddition. The previously unknown absolute and relative configurations were established, and the biological profile was specified more precisely.

Pentaphosphaferrocene coordinates as a π ligand to the large monocation Tl⁺. In addition, one of the phosphorus atoms of each cyclo-P₅ moiety coordinates to a neighboring Tl⁺ ion to give a one-dimensional polymer. Even at low temperatures, fast rotation of the P₅ rings is observed in solution and in the solid state.

Caught in the trap: Two different routes to the thermally unstable phosphinidenoid complex I are described, and chemical evidence for this novel intermediate is provided through selective reactions. For example, methyl iodide, dimethylcyanamide, or butyraldehyde furnished complexes II, III, and IV (see scheme) under very mild conditions.

Cut it out! Convenient procedures have been delineated for the synthesis of optically active, functionalized 1,1-diarylethanes by decarbonylation of β,β-diarylpropionaldehydes. The process can be conducted as a one-pot 1,4-addition/decarbonylation sequence. Aldehydes are used as removable steering groups in this new strategy for the preparation of optically active building blocks.

Slick silicon: A low-molecular-weight silane (C₁₃H₂₀Si, 204.38 g mol⁻¹) with silicon-centered chirality is capable of discriminating enantiomeric rhodium–substrate complexes in dehydrogenative SiO coupling reactions with outstanding selectivity factors (see scheme, s=selectivity factor).

Self-activation: N-Glycosyl imines A of planar chiral [2.2]paracyclophane carbaldehydes act as efficient enantioselective organocatalysts for the Strecker synthesis of α-amino nitriles, although they do not contain a hydrogen-bond donor or a Brønsted acid function. They activate themselves by deprotononation of hydrogen cyanide and catalyze the formation of both aliphatic and aromatic amino nitriles with high enantioselctivity.