Angewandte Chemie International Edition

A unified synthetic strategy to prepare four hasubanan alkaloids, including hasubanonine (depicted), is described by S. B. Herzon et al. in their Communication on page 8863 ff. The synthesis features the application of 5-trimethylsilylcyclopentadiene as a removable, stabilizing stereocontrol element. This controlling group serves to set the absolute configuration in the products and is thermally cleaved at approximately 80 °C lower than the parent cyclopentadiene adducts.

DNA-based hybrid materials when integrated into nanodevices can serve as conductive biocompatible bridges that may interface electronic circuits with biological systems. As X. Guo, M. Shionoya, and co-workers report in their Communication on page 8886 ff, the electrical conductance of individual metallo-DNA duplexes bridging a carbon nanotube gap can be measured and switched by use of Cu²⁺ ions.

Unlike native DNA a DNA template containing a destabilizing modification dissociates from the templated ligation product after its formation. As reported by J. M. Gibbs-Davis et al. in their Communication on page 8922 ff., such destabilizing templates turn over in enzymatic ligation reactions, thereby leading to multiple strands per template. Consequently, isothermal DNA amplification and even replication can be achieved using ligase, simple destabilizing modifications, and standard DNA functional groups.

“My favorite place on earth is with friends and family. The greatest scientific advance in the next decade will be the union of directed evolution and metal catalysis. …” This and more about Michael J. Krische can be found on page 8782.

Wiley-VCH, Weinheim 2010. 282 pp., hardcover € 119.00.—ISBN 978-3527324705

A chemical legacy: Keck and his team have chemically pursued the bryostatin 1 structure with great vigor in recent years and, in late 2010, they finally completed their quest of developing a short and efficient total synthesis of this complex natural product (see structure). The present Highlight provides a brief but nevertheless detailed overview of the Keck synthesis and its chemical legacy in terms of new reactions.

Direct catalytic enolate generation from unactivated carboxylic acid derivatives may provide new routes for asymmetric carbon–carbon bond formation (see scheme). Recent studies demonstrate the potential of silicon catalysts or promoters in this endeavor, and this is best illustrated by a Mannich-type reaction of simple amides.

Efficient and benign bioconjugation: Cu^I-catalyzed azide–alkyne cycloaddition (CuAAC) is an established coupling method because of its high reliability and straightforward experimental procedure. However, the Cu catalyst has often proved detrimental to proteins, nucleic acids, and polysaccharides. Cu^I ligands and Cu-free strain-promoted procedures (SPAAC) have been developed that are efficient and avoid degradation of the resulting bioconjugates.

Phosphorus and azides have a high affinity for one another. This discovery has led to the development of various phosphorus-containing bioconjugation probes. At present, traceless, nontraceless, and phosphite Staudinger ligation probes are frequently applied. The current status of their utilization in life sciences and materials science is described in this Review.

Proceed with caution: The use of fluoride starting materials and SO₂ as a solvent yields neat triazides M(N₃)₃ (M=Ga, In, Tl), thus firmly establishing the existence of thallium triazide. In CH₃CN, the new M(N₃)₃⋅CH₃CN donor–acceptor adducts were obtained. Reactions of the triazides with tetraphenylphosphonium azide in CH₃CN yields exclusively the novel [Ga(N₃)₅]²⁻, [In(N₃)₆]³⁻ and [Tl(N₃)₆]³⁻ anions (see picture, M green, N blue).

Moonlight metal: The valence-precise compound Rb₄Sn₅P₄Se₂₀ (see picture, Rb blue, Sn green, P black, Se red) is the first metallic selenophosphate. It features a new structure hybrid of “conducting” [Sn₅Se₈] layers and “insulating” [P₂Se₆] ligands. It shows the highest electrical conductivity among the chalcophosphates and an extremely low thermal conductivity of 0.44 W m⁻¹ K⁻¹ at room temperature.

Guilty as charged is the verdict for anionic Ir complex [Ir(bpa−2 H)(cod)]⁻ in its reactions with Pd^II compounds. The net transfer of two electrons from the Ir complex to Pd allows easy preparation of di- and trinuclear π-imine-coordinated Pd⁰ compounds such as [{Ir(PyCH₂NCHPy)(cod)}₂Pd] (see picture; C white, Ir red, N blue, Pd yellow). bpa−2 H: doubly deprotonated form of N,N-bis(2-picolyl)amine (bpa); cod: 1,5-cyclooctadiene.

Taking a new turn: An asymmetric Suzuki–Miyaura coupling of 1-bromo-2-naphthalenephosphonic esters with o-methyl-substituted phenylboronic acids proceeds with high enantioselectivity in the presence of high-molecular-weight helically chiral polyquinoxaline-based phosphines (PQXphos) bearing pendant diarylphosphino groups.

On the GO: The basal plane allylic alcohol functionality of graphite oxide (GO) can be converted into N,N-dimethylamide groups through an Eschenmoser–Claisen sigmatropic rearrangement by using N,N-dimethylacetamide dimethyl acetal. Subsequent saponification of these groups affords the carboxylic acids (see picture), which, when deprotonated, electrostatically stabilize the graphene sheets in an aqueous environment.

Springing the trap: A pH-responsive mesoporous silica nanoparticle with a calcium phosphate (CaP) pore-blocking coating was developed by enzyme-mediated surface mineralization under mild conditions. Upon exposure to cellular lysosomal pH, guest anticancer drug was released from the pore by dissolution of the CaP pore blocker (see picture; HAp=hydroxyapatite).

The indium family tree: The discovery of an elusive dimeric indium cluster together with super-trimeric indium clusters in five porous indium–organic frameworks reveals the systematics of indium-based building blocks and their cooperative and competitive roles in the crystallization of chiral and achiral porous frameworks. One of these materials has the smallest possible charge-balancing organic cation and a very high Langmuir surface area.

Maximized divergence: The hasubanan alkaloids given in the scheme have been synthesized in eight or nine steps from the aryl azide 1. The utility of 5-trimethylsilylcyclopentadiene as an easily removed, stabilizing stereocontrol element has been demonstrated.

Four birds with one stone: A palladium catalyst/potassium carbonate/pivalic acid system enables direct arylation of porphyrins by aryl bromides (see scheme; Ar′=3,5-tBu₂C₆H₃). The CH arylation shows excellent β selectivity and does not require porphyrin prefunctionalization, hence representing an extremely efficient method for rapidly providing a series of new β-arylated porphyrins.

Ion-mobility mass spectrometry has been explored as a new technique in the analysis of polyoxometalates and was utilized for the differentiation between photoswitchable isomers of organic–inorganic hybrid compounds (see picture).

In the mix: Au–Pd alloy, Au@Pd core–shell, Pd, and Au nanocrystals (NCs) with an identical octahedral shape and with similar NC size were prepared to examine exclusively the effect of atomic distribution on the catalytic performance of NCs (see picture). The catalytic activities and stabilities toward formic acid oxidation highly depend on the atomic distribution in the NCs: Au–Pd alloy > Au@Pd core–shell > Pd ≫ Au NCs.

Twisted crystals: Upon crystallization, achiral polymers can form chiral crystalline lamellae, such as right- and left-handed helicoids. The chiral parameter imparted by crystallization is the chain tilt with respect to the lamellar normal. Thus, lamella having crystalline stems tilted to the right from the normal to the basal plane will form right-handed helicoids, and vice versa.

Bridging the gap: The electrical conductance of individual metallo-DNA duplexes that bridge a carbon nanotube gap can be measured and switched by use of Cu²⁺ ions (see picture, yellow sphere: Cu²⁺). These studies form the basis for new exciting research that interfaces molecular nanodevices with biological systems.

A matter of size: A dramatic change occurs between the reactivity of Pu^III and Am^III centers in molten boric acid. The resulting complexes display different inner-sphere ligands and different coordination environments (see Pu[B₄O₆(OH)₂Cl] and Am[B₉O₁₃(OH)₄]⋅H₂O in the picture).

For the big screen: An alcohol oxidase/peroxidase-based screen for combinatorial catalysis produces a signal in the visible region and in real time. A targeted high-throughput screen uncovered a bromometalation/carbocyclization route to bicyclic terpenoid cores and a thiocyano palladation/carbocyclization for the ready installation of vinyl thiocyanates.

A flow process for Pd-catalyzed CF bond formation is described. A microreactor with a packed-bed design allows for easy handling of large quantities of insoluble CsF with precise control over reaction times, efficient mixing, and the ability to safely handle elevated temperatures and pressures. A variety of aryl triflates, including heteroaryl ones, were converted into aryl fluorides in short reaction times (see scheme).

Distinctly different: Two 1-oxa-2-silacyclopentenes and a saturated congener have been synthesized and demonstrated to provide access to type II anion relay chemistry (ARC) through a fundamentally new mechanistic pathway. Similar to previous studies, but contrary to initial hypothesis, Brook rearrangement additives (hexamethylphosphoramide and CuI) are necessary to promote Si migration and anion capture.

α versus γ: [CpFe(CO)(PCy₃)(BNCMes₂)]⁺, synthesized by halide abstraction, represents the first example of a BN allenylidene analogue, and features an unsaturated MBNC π system. Although DFT calculations show significant LUMO amplitude at the γ (carbon) position, primary reactivity towards nucleophiles occurs at the sterically less hindered α (boron) center.

Catalyzing concept: Methyl halides have been used to disperse large (around 20 nm) gold nanoparticles supported on carbon into dispersed gold atoms/dimers at low temperature and atmospheric pressure (see picture). The process occurs through the progressive removal of gold–halogen entities from the metal nanoparticles and a gradual decrease in the size of the gold nanoparticles on the minute timescale.

Gold takes to water: The synthesis of amides directly from alcohols and amines was realized by using a water-soluble Au/DNA nanohybrid as the catalyst. The interactions between the gold nanoparticles, DNA, and water lead to high catalytic efficiency under mild reaction conditions. The wide substrate scope includes less-basic aromatic amines, and this catalyst is recyclable.

Learning to let go: Introducing destabilizing modifications into a DNA template leads to turnover in a DNA-templated ligation reaction. By incorporating a cross-catalytic cycle, self-replication was also achieved, with one target able to make 32 copies of itself (see picture). This destabilization approach represents a general method for incorporating amplification into DNA ligation processes using T4 DNA ligase.

In control: The title reaction has been shown to be highly general and efficient, thus exhibiting valuable potential synthetic utility (see scheme; DMF=N,N-dimethylformamide). Isotope labeling and two proposed mechanistic pathways, which invoke a Pd^II/Pd^IV catalytic cycle, show divergent CN and CO bond formation.

Oxazole new world: A gold-catalyzed intermolecular reaction of pyridine-N-aminides with ynamides can be used to prepare trisubstituted 1,3-oxazoles with a variety of functional groups. This formal [3+2] cycloaddition employs robust conjugated N-ylides as N-nucleophilic N-acyl nitrene equivalents for a highly chemoselective and regioselective addition across electron-rich CC triple bonds.

Lost in the shuffle: An unprecedented rearrangement of the title compounds proceeds by the simultaneous rhodium-catalyzed cleavage of aryloxy CO and aldehyde CH bonds (see scheme). The reaction tolerates the presence of various catalytically reactive substituents such as aryl halides, nitrile, and esters.

High or low? A square Fe^II₄ compound exhibits complete thermally and optically activated transition from four low-spin (LS) centers to four high-spin (HS) centers in two steps (see plot of magnetic susceptibility). Reversible desorption and resorption of guest water molecules causes a single-crystal-to-single-crystal transformation.

A familiar ring? Highly N²-selective arylation of 4,5-unsubstituted and 4-substituted 1,2,3-triazoles was achieved for the first time by the Pd/1 catalyst system. A wide range of N²-aryl-1,2,3-triazoles were prepared from aryl bromides, chlorides, and triflates with excellent N² selectivity (see scheme). Density functional theory calculations suggest that the formation of N²-arylated 1,2,3-triazoles is favored kinetically. dba=dibenzylideneacetone, Tf=trifluoromethanesulfonyl.

Take five: A new method employing aryl halide carbonylation to directly access heterocycles has been described (see scheme). In a single palladium-catalyzed reaction the catalyst mediates two consecutive carbonylation steps, thereby converting five components (aryl iodide, two units imine, and two units CO) into an imidazoline ring.

It all adds up: The title reaction was developed for the synthesis of chiral tetrahydroisoquinoline derivatives with a tetrasubstituted carbon center at the C1-position (see scheme, Bz=benzoyl, pybox=2,6-bis(2-oxazolinyl)pyridine). The reaction was facilitated effectively by the co-catalyst system composed of copper(I)/Ph-pybox and an axially chiral dicarboxylic acid.

As easy as α, β, γ, δ: The title reaction unexpectedly resulted in the stereoselective synthesis of bicyclo[3.1.0]hexenes (see scheme). The high level of stereoselection is attributed to a mechanistic pathway involving the oxidative cyclization of nickel(0) with α,β,γ,δ-unsaturated ketones and alkynes, and the subsequent intramolecular carbonickelation.

Handle with care: CL-20, a high-power explosive suffering from high sensitivity, has been cocrystallized with TNT to produce a novel high-power, low-sensitivity explosive. This cocrystal can be used directly for explosives applications or stored in this insensitive form then activated by heat to return it to its high-sensitivity form.

Biomass breakdown: The reactivity of recalcitrant cellulose towards hydrolysis is enhanced by pretreatment with a nonthermal atmospheric plasma. Glucose was produced in up to 25 wt % yield from microcrystalline cellulose and α-cellulose (see picture). This technology is also applicable to the deconstruction of starch and inulin.

The novel CuCl₂-catalyzed title reaction of enynes has been developed for synthesizing substituted naphthoquinones (see scheme; DMA=dimethylacetamide). The method represents the first example of a copper-catalyzed enyne oxidative cyclization for constructing 1,4-naphthoquinones by the incorporation of two oxygen atoms into the organic framework from molecular oxygen and water.

Radical protection makes a biradical: High-temperature-stable biradicaloids [P(μ-NR)]₂ (R=Ter, Hyp) were isolated from [ClP(μ-NR)]₂ when mild reducing agents were employed. The bulky substituents prevent dimerization. Ter=2,6-Mes₂C₆H₃, with Mes=2,4,6-Me₃C₆H₂; Hyp=(Me₃Si)₃Si.

A simple and very efficient chiral aqua iridium(III) diamine complex leads to excellent enantioselectivities in the asymmetric transfer hydrogenation of various α-cyano and α-nitro ketones. The catalyst provides the ortho-substituted aromatic alcohols with especially high ee values. The diamine ligands can be used directly as chiral ligands; conversion into the corresponding sulfamide is not necessary.

The missing member [Cp′′₂Zr(η²-P₃CtBu)] (Cp′′=η⁵-C₅H₃tBu₂) of the phosphorus-containing bicyclobutane zirconium complex family was synthesized by reaction between tetraphosphazirconocene derivative [Cp′′₂Zr(η²-P₄)] and a phosphaalkyne with the release of a formal P₂ unit. Synthetic evidence of another unknown isomer [Cp′′₂Zr(η²-P₂(CtBu)₂)] was found; according to DFT calculations, it is the stable form if a Cp′′₂Zr moiety is used.

Artificial oligo(ethylene amino) acids, together with selected natural amino acids and fatty acid modifications, have been used for the solid-phase-assisted synthesis of polymers with precise sequence, topology, and modifications (see picture). First proof-of-concept studies demonstrate the high potential of such polymers in pDNA and siRNA delivery. K=lysine, A=alanine.