Angewandte Chemie International Edition

A powerful combination of two synthetic methods has advanced the art of organic synthesis like few other reactions. In their Reviews on page 4442 ff. and 4490 ff. K. C. Nicolaou and co-workers illustrate how palladium-catalyzed cross-couplings and metathesis-based reactions, respectively, have blossomed into powerful tools for carbon–carbon bond formation in the total synthesis of natural products.

Rule of thumb: Deciding the fate of drug candidates after an estimate of oral bioavailability depends on how heavily the selection parameters are applied. A retrospective analysis of medications on the market has shown that lipophilicity, percent polar surface area, and the number of H-bond donors are properties that have remained relatively constant over the years, and are clearly the most important physicochemical determinants.

Copper complements palladium as a catalyst of asymmetric allylic substitutions (see scheme). Palladium catalysis requires soft nucleophiles to ensure high stereo- and regioselectivity, whereas hard nucleophiles such as Grignard and organozinc reagents may be used under copper catalysis. Vast progress during the last decade reveals the promising future of copper catalysis in this asymmetric transformation.

The virtues of the palladium-catalyzed cross-coupling reactions come alive in this stimulating Review article as the authors highlight a number of total syntheses featuring these important carbon–carbon bond-forming reactions.

The benefits of metathesis reactions (alkene, enyne, and alkyne) are made apparent in this stimulating Review article. The authors highlight a number of total syntheses featuring these important carbon–carbon bond-forming reactions.

Seeing smells: Highly selective discrimination between closely related amines has been demonstrated by using an array of chemoresponsive dyes (see picture). Hierarchical classification of amines based on their colorimetric response is successful and matches that expected from qualitative structural and electronic considerations. High sensitivity (ca. 100 ppbv) has been shown for the detection and discrimination of amines.

Complete removal of interstitial water molecules from various foam films of amphiphilic compounds results in self-standing bilayer membranes. The dried foam films (DFFs) in the micrometer to submicrometer range (see picture) are stable even under ultrahigh-vacuum conditions and at temperatures higher than 100 °C.

A new concept for catalytic reactions in aqueous media is demonstrated by using a temperature-responsive polymer support, poly(N-alkylacrylamide), which is converted into a catalyst by assembly with phosphotungstic acid. At high temperature, the catalyst is highly active in the oxidation of alcohols with H₂O₂ owing to the formation of emulsions, whereas the product and catalyst are easily separated at low temperature (see scheme).

Cores to celebrate: At 370 °C, Pt@Cu core–shell nanoparticles rapidly alloy but the reciprocal core–shell nanoparticles, Cu@Pt (see STEM images, left: Cu spectral map; middle: Pt spectral map; right: bright-field image), are kinetically stabilized and show high activity and selectivity for NO reduction.

Stuck in the middle: Supramolecular host–guest cages of general formula [BF₄⊂(RCN)₂Co₂L₄](BF₄)₃ with L being a di(benzimidazole)-1,4-phenylene derivative (R=Me, Et, Ph) have been prepared. An encapsulated BF₄⁻ anion (B yellow, F pale green; see structure) is locked firmly inside the cage and plays a pivotal role as a template around which the Co^II ions (gray) and L ligands (ball-and-stick representation) self-assemble.

Generation of diversity: An oligosaccharide library can be constructed from glycopeptides by repeating incomplete glycosyltransferse (GTs) reactions in a single tube (see picture). Each product has a different molecular weight (MW). Therefore, the structure of each component in the library can be identified immediately by mass spectrometry alone. The differently colored shapes in the picture symbolize different glycosyl residues.

Strong photoluminescence in the blue region of the visible spectrum was observed for a dispersion of allylamine-capped silicon quantum dots in water. Their ease of synthesis and optical properties make them excellent candidates for biomedical applications, as demonstrated by their incorporation inside the cytosol of HeLa cells (see microscopy image, the inset shows the fluorescence from the silicon quantum dots on excitation with UV light).

A change in direction: The photocurrent generated by CdS nanoparticles attached by means of a double-stranded DNA linker to a gold electrode is reversibly switched between the anodic or cathodic direction (see graphic) depending on the redox state of the methylene blue intercalator.

Any which way, but not loose: A range of diverse noncovalent binding interactions are observed with a [2]rotaxane (see structure) and a [2]catenane that are not found with similar but not mechanically interlocked fragments. (C (macrocycle) turquoise, other C atoms yellow, O red, N blue, H gray, F green, S orange.)

Optically active α,β-diamino acids are prepared under asymmetric phase-transfer reaction conditions from a glycine Schiff base and N-protected imines with a tartrate-derived diammonium salt (TaDiAS) as the phase-transfer catalyst (see scheme; Boc=tert-butoxycarbonyl). Chemoselective deprotection of the N atoms allows straightforward transformations of the α,β-diamino acid products to be carried out.

A question of symmetry: Unlike other mono-metallofullerenes, the cage structures of Eu@C₈₂ (isomers I and III) have been shown to have C_s (no. 6) and C_2v symmetry, respectively, by the maximum entropy method using synchrotron X-ray powder diffraction data. In both isomers (see structures) the Eu ion (turquoise) is located near the top of the carbon cage adjacent to a CC double bond.

Finding the right pathway: Reaction of isotopomers of ethylene with acetate species (see scheme) adsorbed on a Pd(111) surface in ultrahigh vacuum has shown that vinyl acetate is produced by insertion of ethylene into the acetate species to form an acetoxyethyl intermediate, which decomposes by β-hydride elimination to yield vinyl acetate.

A large guest for a small host: The tweezering process about the bipyridinium core of a dendrimer by a molecular tweezer (see picture) has been studied electrochemically and by fluorescence spectroscopy and is found to be quite similar to the threading/dethreading processes observed with wire-type bipyridinium-based units and ring-shaped molecules.

Polymer brushwork: The collapse of polyelectrolyte brushes in salt solutions combined with binding interactions and ion-size-exclusion effects is used in the design of smart polymer surfaces that can be switched between permanently collapsed or extended states with different surface properties (see picture)—a step toward the use of surface-confined polyelectrolytes as nanoactuators.

Higher activity with larger pockets: The figure shows a superposition of intermediates that occur in acyl transfer to (S)-1-phenylethanol catalyzed by Candida antarctica lipase B (CALB). Wild-type CALB cannot accomodate the phenyl group (gray) in the stereospecificity pocket and form all of the catalytically essential H bonds. The Trp 104 Ala mutation liberates the volume in yellow, the S enantiomer is easily fitted, and the specificity constant increases by a factor of 130 000.

Oxidative decomposition of toxic pollutants (such as acetaldehyde and isopropyl alcohol), decomposition of water, and photocurrent generation can all be achieved with visible light. Nano-islands of p-type CaFe₂O₄ interfacing with bulk n-type PbBi₂Nb_1.9W_0.1O₉ (shown) form photocatalytic nanodiodes that demonstrate high stability and high activity for such applications.

Feature film: Mesoporous alumina thin films synthesized with a polymeric template have more than 50% porosity, a narrow pore-size distribution, high accessibility, and high thermal stability up to 900°C. The inorganic network is composed of sintered nanocrystalline γ-Al₂O₃ particles, and the pores are ellipsoidal with a face-centered cubic mesostructure (see image).

Divalent Group 14 salts react with the [Na(thf)_x]⁺ derivative of the terminal niobium phosphide anion [PNb{N(Np)Ar}₃]⁻ (Np=neopentyl, Ar=3,5-Me₂C₆H₃) to give complexes of the form [(μ₂:η³,η³-cyclo-EP₂){Nb[N(Np)Ar]₃}₂] (E=Ge, Sn, and Pb; see structure). The bridging {cyclo-EP₂} units in these complexes can be considered as neutral 2π-electron three-membered rings that are isolobal to the cyclopropenium ion.

A high-yield one-pot synthesis of S-linked glycosyl amino acids 1 has been developed (see scheme; DMF=dimethyl formamide) and used in the solid-phase synthesis of S-linked glycopeptides. This approach has been shown to be efficient for the synthesis of various S-linked glycosyl amino acid building blocks.

Quite universally: The chiral trigonal-bipyramidal Al(salalen) complex 1 was synthesized and found to be an efficient catalyst for enantioselective hydrophosphonylation of various aldehydes with dimethyl phosphite (see scheme). This is the first example where a molecular catalyst can be applied to the reactions of both aromatic and aliphatic aldehydes with enantioselectivities greater than 80 % ee.

A natural product anticipated through total synthesis! Ocellapyrone A was obtained in the laboratory several months before the structure of this unusual natural product (see scheme) was reported. An isomerization/8π–6π electrocyclization cascade was used for the formation of the natural product from a polyene precursor. The synthesis of ocellapyrone B from a diastereomer of ocellapyrone A was also performed.

With a little help from the ferrocenyl catalyst ((−)-1), a wide array of α-arylalkanoic acid derivatives can be produced from the catalytic asymmetric coupling of ketenes with aldehydes (see scheme). The enol esters are readily transformed into other useful families of compounds such as carboxylic acids and alcohols.

Ever-increasing circles: Seven-membered-ring ketones are constructed by a rhodium(I)-catalyzed arylative ring-expansion reaction of alkyne-substituted aryl cyclobutanones, in which two CC bond-forming and one CC bond-cleaving events occur consecutively (see scheme).

Two is better than one: Novel chiral phosphine–olefin ligands 1 a and 1 b act as bidentate ligands with some transition metals and have proved to be highly effective in the rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to maleimides with high enantioselectivity (see scheme).

A stable environment: A [Cu(NH₃)₂]₂²⁺ dimer with weak cuprophilicity is stabilized in the cavities of a supramolecular framework (see structure). This Cu^I dimer is otherwise unstable, so stabilization within a supramolecular matrix offers an unprecedented opportunity for systematic studies of the isolated dimeric species, either in the ground state or the excited state.

A sulfide surprise: The analysis of Zn^II–, Cd^II–, and Cu^I–MT recombinant preparations of metallothioneins (MTs) from many organisms provides clear evidence that sulfide ions are present in nearly all their physiologically stable Zn^II–MT and Cd^II–MT complexes (see picture), but in none of the Cu^I–MT species. The features of the MT complexes are in good correlation with those reported for plant and yeast Zn^II–or Cd^II–γ-glutamyl peptides.

Lost control: The rationalization of the ambident reactivity of NO₂⁻ by the change between charge control to orbital control has to be revised. S_N1-type reactions of carbocations with NO₂⁻ give kinetically controlled product mixtures only when these reactions proceed without activation energy (diffusion control). Activation-controlled S_N1 alkylations are reversible and lead to the thermodynamically more stable nitro compounds.

Trisubstituted allylic pentafluorobenzoates react with diorganozinc reagents in the presence of CuCN⋅2 LiCl to provide alkenes bearing a chiral quaternary center in α position (>95 % ee). These alkenes are readily converted into chiral tertiary alcohols or into chiral amino alcohols by a straightforward sequence of ozonolysis followed by Curtius rearrangement (see scheme).

Launching a probe: Introducing individual tyrosine residues labeled with ¹³C at the C4 position of the phenol ring (Y11 and Y19 in the picture) shifts the resulting tyrosine IR band to lower frequencies. This opens the door to the simultaneous monitoring of local conformational changes in different regions of proteins by IR spectroscopy, as demonstrated with a chemically synthesized analogue of a WW domain.

A molecular switch based on a resorcin[4]arene cavitand undergoes reversibly very large, geometrically precisely defined molecular motion (see picture). Controlled switching between the contracted (linear extension ≈7 Å) and the expanded (linear extension ≈7 nm) states is induced by pH or temperature changes and was observed by ¹H NMR spectroscopy and fluorescence resonance energy transfer (FRET).