Angewandte Chemie International Edition

An extremely attractive method for forming C(sp³)−C(sp²) bonds in complex molecular settings is the B-alkyl Suzuki–Miyaura reaction (see scheme; 9-BBN-H = 9-borabicyclo[3.3.1]nonane; the dashed line indicates that intramolecular reactions are also possible). The regio-, chemo-, and stereoselective nature of this reaction has been used in a number of syntheses of natural and non-natural compounds. An intricate knowledge of the mechanism of this reaction provides the basis for future advancements in this field.

Copper enzymes are involved in dioxygen binding, activation, and reduction to water. The oxygen intermediates in these enzymes exhibit unique spectroscopic features, which reflect new geometric and electronic structures that play key roles in catalysis. Structure/function correlations are developed and reaction mechanisms are defined on a molecular level. The figure shows the calculated frontier orbitals of the μ-η²:η²-side-on bridged-peroxo Cu and the bis-μ-oxo-Cu intermediates, which activate π and σ electrophilic attack on substrates, respectively.

The synthesis of optically active natural products and pharmaceuticals with quaternary stereocenters is a particular challenge. The potential of new stoichiometric and catalytic asymmetric reactions can be proved by their suitability for the enantioselective generation of such fully substituted carbon centers, such as, for example, in the compounds shown.

Picture(s) of Fritz Haber: Rolf Hochhuth, Tony Harrison, and André Malraux—three very different writers—have portrayed Fritz Haber in their novels and plays. The picture may not please chemists. Several biographies and an essay by the historian Fritz Stern have also dealt with Haber's tragic life. Should we accept these as literary portraits, if they are not to our liking? Or struggle with them? And in Haber's case would this be justified?

What connects the author Marcel Proust, the Chemistry Nobel Laureate Henri Moissan, and the fraudulent engineer Henri François Lemoine? Moissan was obsessed with the idea of preparing artificial diamonds, Lemoine alleged that he had improved the Moissan technique, which only produced diamond dust, and Proust first invested a part of his wealth in the alleged diamond synthesis and then exploited the scandal in a literary work.

Far from being a well-understood reaction, the enantioselective hydrogenation of prochiral olefins with Rh–and Ru–bisphosphane catalysts (see picture, M=Rh, Ru) has recently shown some surprises. Among them are a catalytic cycle featuring initial addition of hydrogen to the catalyst and not the catalyst–substrate complex as well as a purely ionic mechanism.

Which scaling connects the number of conformers of a protein with the number of residues? The authors both explore this question and van Gunsteren et al. produce additional arguments to those in their original paper. Although the authors do not agree on the “scaling law”, they both acknowledge the importance of finding the correct answer as it has a great influence on the chance of simulating protein folding with reasonably good models.

Which scaling connects the number of conformers of a protein with the number of residues? The authors both explore this question and van Gunsteren et al. produce additional arguments to those in their original paper. Although the authors do not agree on the “scaling law”, they both acknowledge the importance of finding the correct answer as it has a great influence on the chance of simulating protein folding with reasonably good models.

A transition metal based biomimic approach is used to realize multistep reactions, composed of multicomponent systems, in a single-pot synthesis of chiral diols mediated by a trifunctional (Pd, Os, W) catalyst anchored to a single matrix (see scheme; LDH=layered double hydroxide, (DHQD)₂PHAL=1,4-bis(9-O-dihydroquinidinyl)phthalazine, NMM=N-methylmorpholine).

Even under a pressure of 46 GPa, the low-symmetry lone-pair structures of isoelectronic TlF and PbO (see picture for β-PbO), classic examples of systems with a stereochemically active lone pair, resist transformation into the corresponding high-symmetry NaCl and CsCl structures. Ab initio calculations allowed a simple bonding picture for lone-pair structures involving inert-pair elements to be developed.

The branched DNA structure 1, in which a transition metal center resides at the branch point and joins two parallel DNA strands, was synthesized by a convergent solid-phase approach. Complex 1 efficiently hybridizes with complementary DNA to generate transition metal linked DNA duplexes. This opens the door to using the geometries of transition metal complexes to direct the association of DNA into novel motifs.

Proton transfer from ammine or amide ligands to vinylamine-type π systems in intermediary titanacycles (see picture) of allene and alkyne hydroamination reactions is predicted by DFT model calculations. The weaker coordination of alkenes to the Ti=N fragment, the lack of a π system in the titanacycle, and thus the necessity of direct Ti−C bond protonation rationalize a higher barrier for alkene hydroamination.

C₃-symmetric lactams in a tube: Specially designed rigid disc-shaped macrolactams self-assemble as endless tubes by means of backbone–backbone hydrogen bonds and van der Waals contacts (see scheme). All the tubes with very strong dipoles further aggregate in a parallel fashion and all the dipoles are still oriented in the same direction.

Pores for cluster catalysts: Nanoparticles of both Ru₅Pt and Ru₁₀Pt₂, uniformly distributed along the inner walls of mesoporous silica, exhibit high catalytic performance in the single-step hydrogenation of dimethyl terephthalate (DMT, to 1,4-cyclohexanedimethanol (CHDM); see scheme), of benzoic acid (to cyclohexane carboxylic acid), and of naphthalene (in the presence of sulfur) to cis-decalin.

Collective on/off behavior and different spectral behavior has been identified for individual molecules of different isomers (see for example the fluorescence spectra for two isomers as a function of time) with three perylenedicarboximide chromophores. In 8 % of the dendrimer molecules, the chromophores interact to form an excimer-like structure which possess a higher rate of intersystem crossing than the rest of the molecules. This is the first time that this phenomenon has been proven experimentally at the single-molecule level.

The simple replacement of 2′-OH by 2′-OMe groups leads, in certain RNA structures, to a significant strengthening of important solute–solvent interactions. Molecular dynamics simulations uncover the complexity of effects associated with the insertion of hydrophobic groups into hydrophilic systems (the arrow indicates a long-lived bridging water molecule located in the shallow groove of a 2′-OMe(GpC) base pair step). Green=skeleton of cytosine, black=skeleton of guanine, red=oxygen atoms of water and of shallow groove carbonyl groups, blue=shallow groove nitrogen atoms, cyan=hydrogen atoms of OMe groups.

Copper gets into the ring: A decanuclear cyclic Cu^II complex is synthesized by direct treatment of CuCl₂ with a fluorinated amino alcoholate containing one secondary and one tertiary nitrogen donor (see space-filling diagram; Cu light blue, Cl yellow, O red, N dark blue, C gray). Possible factors that lead to the self-assembly of the unique molecular wheel are discussed.

Rational design of a malaria vaccine may result from the structure–immunogenicity relationship of analogues of peptide 1585, a protein sequence located at the N-terminal end of the P. falciparum 42-kDa merozoite surface protein-1. Altering a few amino acids in peptide 1585 (left) induces immunogenicity and protectivity, and changes the 3D structure, as shown for one of the analogues synthesized (right).

Delightful order and beauty is exhibited by novel supramolecular architectures constructed from preorganizing rigid-rod molecules which first self-assemble into β-barrel tertiary structures (left) and then transform into higher-order quaternary structures (right), that is, “rigid-rod β-fibrils”.

A star is born: Size-selected, end-functionalized single-walled carbon nanotubes react with amine-terminated dendrimers to form star-shaped objects (see schematic representation). Analysis of the nanotube stars by atomic force microscopy and scanning electron microscopy show that they exhibit a peculiar response to electron beams.

A slice of life: Individual, fluorescently labeled DNA molecules are cut by a restriction enzyme into a sequence-specific fingerprint-like pattern and the time course of the reaction is analyzed by fluorescence microscopy. As shown in the picture, all the cuts occur one after another from one end to the other along the DNA molecule.

Moving individual molecules: Up to 250-nm long polystyrene chains with fourth generation dendrons at each repeat unit were synthesized, individualized on highly oriented pyrolytic graphite (HOPG), and manipulated into a stretched linear conformation by a scanning force microscope tip (see images, arrow indicates direction of movement).

An ACID test for aromaticity: A number of criteria prove that tris(ethylene)nickel(0) and tris(ethyne)nickel(0) are aromatic compounds. The ligands strongly interact in the periphery and are “on the way” to trimerizing to cyclohexane and benzene, respectively. The electronic structure of these complexes (see picture, which shows the current density vectors plotted onto the ACID surface of the nickel ethylene complex) sheds light upon the role of Ni⁰ as a catalyst in cyclooligomerization reactions. ACID = anisotropy of the induced current density; a method for visualizing the density of delocalized electrons and for quantifying conjugation effects.

The fabrication of small metal clusters with a scanning tunneling microscope in an electrochemical environment has been simulated with a computer. (The picture shows the copper-covered tip of the scanning tunneling microscope above the Au(111) surface, which is covered by copper.) In the case of copper deposition on Au(111), Cu–Au clusters were formed that are more stable than pure copper. The simulations suggest that the formation of stable clusters by this method can only succeed if the deposited metal and the substrate form a stable alloy.

“Hits” with high quantum yields: The screening of the chromophores of a coumarin library for optical properties allowed the identification of “hits” with high fluorescence quantum yields (see picture) which could be used as fluorescence labels and laser dyes. The generation of the library was facilitated by an efficient method involving the parallel synthesis utilizing Pd-catalyzed cross-coupling reactions.

256 oligomers make up the quaterthiophene library of compounds 1 which was prepared by a combination of parallel and “mix-and-split” syntheses. An automated screening process for the recording of cyclic voltammetric data and subsequent data analysis allowed the development of structure–property relationships on which to base the future design of π-conjugated oligomers.

The multiplicity of the excited state controls the product distribution in the formation of endo/exo-oxetane 3 in the photocycloaddition of aldehydes 1 (R = Ph, Et, Me, iBu) with dihydrofuran 2 (Paternò–Büchi reaction). Whether the singlet or triplet channel dominates is strongly dependent on the temperature, which is therefore critical for the selectivity of the reaction.

Linear and bicyclic glycopeptides occur as intermediates in the biosynthesis of the aglycon of glycopeptide antibiotics of the type shown. Considering the structures of these peptides and those of previously isolated analogues, the sequence of the three oxidative ring-closing steps can be deduced for type-I and type-II glycopeptide antibiotics. Thus, comprehensive insight into the assembly of the aglycon is achieved for the first time.

Ambivalent chemical reactivity is characteristic for molecular phosphorus oxides: They either react in a vigorous and uncontrolled manner or they are practically inert, for example, in attempts at controlled ring-opening reactions. Thus, the spontaneous dimerization of P₄O₆⋅BH₃ to give P₈O₁₂⋅2 BH₃ (see crystal structure) is a real surprise.

Two reaction protocols have been developed for the catalytic dehydrocoupling of secondary phosphanes by the rhodium(I) complex [Cp*Rh{CH₂=CH(TMS)}₂]: In the presence of an olefin, transfer hydrogenation occurs to give the corresponding alkane and the diphosphane. Without the addition of an olefin, the reaction proceeds by loss of dihydrogen but more elevated reaction temperatures must be used [Eq. (1)].

A photolytically induced reaction of AlF with O₂ in an argon matrix afforded the first peroxo and bis-superoxo complexes of aluminum: FAlO₂ and FAl(O₂)₂ (see picture). The compounds were identified and characterized by IR spectroscopy and density functional theory (DFT) as well as ab initio calculations.

Almost 90 years after it was first described by Ludwig Claisen, a catalyzed enantioselective Claisen rearrangement has been implemented for the first time. Chiral copper(II) bis(oxazolines) catalyzed the Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers with enantiomeric excesses of 80–90 % (see scheme).

One of the most enticing natural products isolated in recent years and a serious challenge to synthetic chemists is represented by the potent anticancer agent diazonamide A (1). By utilizing a highly convergent approach, the ABCDEF macrocycle 2 was constructed in only 16 linear steps based on a key intermolecular Suzuki coupling reaction to generate the C₁₆−C₁₈ biaryl linkage and a remarkable SmI₂-induced hetero pinacol coupling cascade sequence.

A strategy for the synthesis of heliquinomycin, a selective helicase inhibitor, hinges on the spirocyclization of precursor 3. Naphthofuran 1 and aldehyde 2 were readily prepared and used in the synthesis of 3. The key steps in the total synthesis of heliquinomycinone (4) include the regioselective dihydroxylation of 3, and a novel spirocyclization under Mitsunobu conditions.

A strategy for the synthesis of heliquinomycin, a selective helicase inhibitor, hinges on the spirocyclization of precursor 3. Naphthofuran 1 and aldehyde 2 were readily prepared and used in the synthesis of 3. The key steps in the total synthesis of heliquinomycinone (4) include the regioselective dihydroxylation of 3, and a novel spirocyclization under Mitsunobu conditions.

Not a classical spin-crossover: The heat capacity of the mixed-valence complex {[(n-C₃H₇)₄N][Fe^IIFe^III(dto)₃]}_∞ (dto=dithiooxalato, see scheme) exhibits a phase transition at 122.4 K as a result of electron transfer, and gives insight into the cooperative phenomena exhibited by the multifunctional material.

Activated by reduction: On treatment with methylaluminoxane (MAO), the Brookhart/Gibson cobalt-based polymerization precatalyst [LCo^IICl₂] is first reduced to [LCo^ICl], subsequently alkylated to [LCo^IMe], and finally converted into the (as yet unknown) active species (see scheme, PE=polyethene).

A bivalent system capable of binding to hybrid DNA sites through simultaneous interaction in the major and the minor groove (see schematic representation) is formed by appropriate linking of the basic region of a b-ZIP protein (GCN4) to a tripyrrole related to the antibiotic distamycin.

A highly simplified synthesis of a tetrasaccharide was possible by a repeated coupling/capture–release cycle. In the first cycle, a glycosyl acceptor (1) bound to a soluble polymer reacted with a glycosyl donor (2) having a chloroacetyl group as a temporary protecting group. Solid-phase capture by a resin-bound thiol group (in 3) was followed by Fmoc removal, which released the polymer-bound disaccharide 4 into the solution phase. Fmoc=9-fluorenylmethoxycarbonyl.

The dominant solution-phase conformation of a polymer can be fixed to a surface (see scheme). Boronic acid appended poly(L-lysine) assumes different conformations in the presence of D-glucose or D-fructose. When the polymer–glucose complex is anchored to a gold surface, an imprinted interface with “molecular memory” for glucose over fructose can be prepared.

Association of streptavidin and two biotinylated polystyrene chains to form protein–polymer hybrids results in “giant amphiphiles” (see first step of schematic representation). Functionality can be introduced by the complexation of other biotinylated molecules to the remaining binding sites of streptavidin (second step).

A Ni₄O₂core based on a “chair” topology forms the central unit of the tetranuclear nickel(II) complex 1, which possesses μ₃-OH⁻ and butane-2,3-dione-monooximate bridges and displays fascinating magnetic properties. The major Ni–Ni interactions in 1 are antiferromagnetic in nature, and the large Ni_core-O-Ni_terminal angle in the core is responsible for driving all the Ni_core spins parallel.

Contrasting calixarenes: Thermodynamically stable and water-soluble calix[4]arene–Ln^III (see picture) complexes may represent a new class of relaxation (Ln=Gd) or luminescent (Ln=Eu, Tb) probes for biomedical studies. The first complete characterization of one of these complexes in water is reported. The Gd^III chelate shows a strong binding affinity with human serum albumin as a result of the cooperative effects of hydrophobic interaction and coordination by donors groups on the protein.

A pseudo-pentagonal kernel is the central unit in the new quaternary intermetallic phase Li₁₀Mg₆Zn₃₁Al₃ (see structure). This unit can form the basis for decagonal and, possibly, icosahedral quasicrystals. The synthesis, crystal structure, and bonding of Li₁₀Mg₆Zn₃₁Al₃ are discussed in detail.

An unusual bonding mode for a porphyrin ligand is seen in the tellurium porphyrin complex prepared by treatment of TeCl₄ with dilithio meso-tetra(p-tolyl)porphyrin [Li₂(ttp)]. The structure of [Te(ttp)Cl₂] (see picture) has a five-coordinate, square-pyramidal geometry involving a distorted tridentate porphyrin ligand and cis-dichloride ligands.

Intramolecular Heck reaction of 3 generates a spiro quaternary C atom—a key step in an efficient synthesis of galanthamine (1). Galanthamine can be readily obtained from the spiro tricyclic dienone 2, which was prepared by nonclassical dehydrogenation of the corresponding α,β-unsaturated ketone.

Starting from coprostanone with a cis A/B ring fusion, the basis for a new class of enantioselective hosts has been established. The trimerization by TiCl₄/ZnCl₂ gave the tri-steroid 1, a C₃-symmetric hydrocarbon that, according to X-ray analysis, contains a deep, chiral cleft.

Guided by 24 drug–DNA NOEs, the complex formed between RHPS4 (a novel fluorinated polycyclic methylacridinium salt with potent telomerase activity) and d(TTAGGGT)₄ has been modeled by using MD simulations with drug molecules intercalated at the ApG and GpT steps. A low-energy structure for the 2:1 complex has a partial positive charge on the acridine 13-N atom (which acts as a pseudo potassium ion) positioned above the center of the G-tetrad (see picture).

Acetonitrile might not be an “innocent” solvent after all: The monomeric Cu^II complex [Cu(dmppy)(en)] (see structure) readily cleaves the C−C bond of acetonitrile under ambient conditions. Previously, heterolytic cleavage of the C−C bond of acetonitrile had only been achieved by phosphane complexes of metals in low oxidation states. dmppyH₂=N,N′-dimethylpyridine-2,6-dicarboxamide, en=ethylenediamine.

A platinum cyclopropyl carbene complex, formed by anti attack of the furan ring on an (η²-alkyne)platinum complex (see scheme), is the key intermediate in the intramolecular reaction of furans with alkynes according to experimental studies and density functional calculations.

A versatile precursor for the assembly of a range of polyol-containing fragments is the silacyclic alcohol 2 that results from the highly enantioselective, catalytic isomerization of diphenylsilacyclopentene oxide (1). The use of this precusor is illustrated with the efficient and highly diastereoselective assembly of acyclic tetraol motifs.

The most basic of aldol constructions, namely the controlled stereoselective self-condensation of aldehydes, has finally found a general solution. Geometrically defined trichlorosilyl enolates of aldehydes display excellent reactivity, near perfect diastereoselectivity, and good (albeit variable) enantioselectivity in their addition to a wide range of aldehydes under catalysis by a chiral bisphosphoramide (see scheme).

Up to five new stereogenic centers (see 2) can be formed in one-pot consecutive three- and four-component coupling reactions starting from a butane diacetal desymmetrized glycolic acid derivative 1. Highly functionalized α-hydroxy acid derivatives are obtained in an easy, fast, clean, and efficient way. LHMDS = lithium hexamethyldisilazide.

Unable to bear the weight of scrutiny, the original structure proposed for (−)-diazonamide A (1) must be revised. A convergent, stereocontrolled total synthesis provided 1, which shows altered physical and spectroscopic characteristics relative to those of a sample of the natural product. Reinterpretation of reported data and new insight indicate that the actual structure of diazonamide A is the aminal-containing (S)-α-hydroxy isovaleric acid conjugate 2. Gratifyingly, a synthetic C11 acetal congener of 2 is, by all biological measures examined, similarly potent and functionally equivalent to the antimitotic natural product.

Unable to bear the weight of scrutiny, the original structure proposed for (−)-diazonamide A (1) must be revised. A convergent, stereocontrolled total synthesis provided 1, which shows altered physical and spectroscopic characteristics relative to those of a sample of the natural product. Reinterpretation of reported data and new insight indicate that the actual structure of diazonamide A is the aminal-containing (S)-α-hydroxy isovaleric acid conjugate 2. Gratifyingly, a synthetic C11 acetal congener of 2 is, by all biological measures examined, similarly potent and functionally equivalent to the antimitotic natural product.