Angewandte Chemie International Edition

Just a handful of good reactions are needed to assemble vast numbers of highly diverse organic molecules. (The graphic shows a simple example.) Yet, this easily accessible structural universe has not been mined by the medicinal chemistry community for its nuggets of desirable function. The requirements for the best reactions that can be employed, examples of such processes, and the philosophy that underlies their use are discussed in this review.

Supramolecular coordination complexes or coordination chemistry supramolecules? Emerging synthetic approches for the construction of supramolecular structures by coordination chemistry (see picture) have led to a rapid expansion of the field of suprarmolecular chemistry. Many structures are now accessible through the general principles that define these approaches, and the applications of the structures formed from them are beginning to be explored.

The ultimate goal of producing esters in 100 % yield from an equimolar reaction of carboxylic acid and alcohol may not be far away: The research groups of Yamamoto and Tanabe have found that effective condensation can be achieved using HfCl₄⋅2 THF and diphenylammonium triflate catalysts, respectively. Although the first catalyst gives near quantitative yields of the esters (91–>99 %), the reaction is moisture sensitive, while the latter catalyst gives lower yields (89–96 %) but requires no dehydration reagents or equipment.

Diverse complex systems may be studied by the new methods in solid-state NMR spectroscopy described herein. These methods use magic-angle spinning (MAS) on samples in oriented bilayers (right picture) and in orientationally disordered samples (left picture). Systems as diverse as uniformly ¹³C,¹⁵N-labeled proteins, model membrane systems, and silk, as produced by the silkworm, can be structurally characterized.

Quantum-chemical calculations at the B3LYP level show that the bulky ligands Ar*=2,6-Ph₂C₆H₃ in Ar*PbPbAr* yield the trans-bent equilibrium structure shown as the lowest lying energy minimum form. There is no Pb−Pb π bond in Ar*PbPbAr*. The parent compounds PhPbPbPh and HPbPbH have doubly bridged energy minima structures.

An alternative to the known thermally induced syntheses of fulvene complexes of early transition metals is now provided by the direct reductive complexation of pentafulvenes to [CpTiCl] fragments. These generally highly diastereoselective reactions (see scheme) enable a broad variation of substitution patterns and establish an extensive subsequent chemistry.

Modeling with paper clips? No, a general method for the fabrication of complex three-dimensional (3D) microstructures is reported. The 3D structure is decomposed into substructures that can be patterned onto separate substrates and then these substrustures are joined to form the desired microstructure. The picture shows an optical micrograph of a free-linked nickel chain mail.

Simple ester derivatives of polycyclic arenes offer access to light-emitting diodes of nearly any visible color by making use of the good charge-transport properties of the columnar liquid crystals of these derivatives. The picture shows the orange–red electroluminescence of a light-emitting diode containing the perylene 3,4,9,10-tetracarboxylic acid ethyl ester (structure shown, R=Et). Through use of multiple layers of different esters light-emitting diodes with almost white luminescence can be obtained.

A Cu^I-mediated coupling of the northern and southern units and a ring-size selective macrolactonization are the key steps in the convergent, first total synthesis of apoptolidinone, the aglycon of the potential antitumor compound apoptolidin. (The wavey lines in the picture are the retrosynthetic disconnections.)

Special carbon! Carbon nanofilaments differ from graphite and soot catalysts in their high stability during the oxidative dehydrogenation of ethylbenzene to styrene (see picture). The high yields of styrene achieved suggest that a first industrial application of carbon nanofilaments in catalysis is possible.

Under mild conditions, a linear polymeric (C₇₀²⁻)_n fulleride was synthesized as single crystals which allow, for the first time, a complete structural analysis of a polymeric fulleride. Starting from the strongest “disturbance” of the cage geometry at the linkage sites, the pronounced alternation of the bond lengths decreases towards the middle of the C₇₀ units (see Schlegel diagram of the C₇₀²⁻ building block; color coding of the bond lengths [Å]: blue <1.39, black 1.39–1.47, red 1.47–1.52 Å, green >1.52).

The selective activation of photolabile protecting groups was made possible by the use of monochromatic light of suitable wavelength. This new approach allowed the orthogonal deprotection of a substrate containing several photosensitive groups (see picture).

New light on the origin of the high enantioselectivities achieved in the Jacobsen–Katsuki epoxidation is shed by the results of density functional calculations. Axial ligation to the metal center not only enhances the epoxidation rate, but in addition leads to highly nonplanar, bent conformations of the active catalyst (see picture).

Synthetic ion channels containing δ-amino acids can become cation selective! δ-Amino acids with a cyclohexylether unit (see structure) were combined with structural motives from gramicidin A and led to channels with a NH₄⁺/K⁺ permeability ratio of >10/1. (The current trace for an NH₄⁺ channel is shown.)

Significantly enhanced binding affinity to C⋅G base pairs without loss of sequence selectivity is achieved by using a nucleotide containing a 2-pyridone and a 2′-O,4′-C-methylene-bridged nucleic acid analogue (P^B, see picture). The degree of stabilization of the triplex formed enables C⋅G interruptions in a homopurine⋅homopyrimidine double-stranded DNA to be detected.

A single, convenient reaction protocol and the same set of readily available starting materials suffice for the modular synthesis of all possible polypropionate diastereomers (see scheme). This general method for the diastereoselective synthesis of syn, anti, and methyl ketone aldol adducts utilizes a powerful Mg^II-mediated, hydroxy-directed nitrile oxide cycloaddition. The free hydroxy group provides an ideal synthetic handle enabling the rapid assembly of complex polyketide structures. TBS=tBuMe₂Si.

Magnesium–bromine exchange to provide the 1-bromo-1-silylmethylmagnesium species is mediated by treatment of dibromomethylsilane with an trialkylmagnesate reagent. The addition of a copper catalyst induces facile migration of an alkyl group to afford an α-silylalkylmagnesium compound, which furnishes α-silyl ketones in good yield upon treatment with acyl chloride (see scheme).

Cobalt and manganese complexes provide access to novel fluoroallyl ligands: Fluorinated bis(enyl) ligands can be easily synthesized by metal-induced dimerization of 1,1-difluoroallene and tetrafluoroallene. By using octacarbonyldicobalt the coupling reaction occurs at the central carbon atom of the allene leading to the formation of fluorinated μ-(η³:η³-2,3-dimethylenebuta-1,4-diyl) ligands such as those in complex 1. Additional products arise from fluoride abstraction and CO insertion reactions. Decacarbonyldimanganese reacts with 1,1-difluoroallene under C−C coupling of the methylene group to give decacarbonyl-μ-(η¹:η¹-1,1,6,6-tetrafluoro-1,5-hexadiene-2,5-diyl)dimanganese.

Plants utilize two different pathways for the biosynthesis of isopentenyl diphosphate, the universal building block of all terpenes (see scheme). Application of compound-specific isotope-ratio mass spectrometry (GC-C-IRMS) to volatile terpenoids allows distinction between the pathways on the basis of natural ¹²C/¹³C ratios.

Inspired by Archaebacterial lipids, transmembrane probes anchor a sensing fluorescent polyene with Ångström resolution deep within a lipid layer (see figure). These new bolaamphiphiles are obtained in good yields from a double cross-coupling between esters with a terminal acetylene group and conjugated 1,ω-dihalopolyenes, followed by partial reduction of the triple bond.

Outperforming fluorescein by far, elongated fluorophores (e.g. 1) give rise to large two-photon absorption cross-sections σ₂ in the visible-red or NIR region and high quantum fluorescence yields Φ (see figure; GM = 10⁻⁵⁰ cm⁴ s photon⁻¹). This opens interesting prospects in the field of two-photon microscopy imaging of cell membranes.

syn to tin is the preferred mode of addition of organolithium reagents to the carbonyl group of cyclic ketones with a β-stannylvinyl group. This remarkable remote control is a consequence of the anchoring of the organolithium reagent by the tin and carbonyl groups (see picture).

Nitroaromatic explosives can be detected in a simple and rapid method by the quenching of the photoluminescence of fluorescent polysiloles. Quenching is achieved by electron transfer from the conduction band of the polysiloles to electron-poor molecules such as picric acid, nitrobenzene, 2,4-dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT). Dilute polymer solutions can also be employed as a forensic spray-on reagent to visualize TNT or picric acid residues under a UV lamp (see picture of the print of a nitrile-gloved hand that had been in contact with TNT).

Proposed as intermediates in the catalytic oxidation of olefins to ketones, 3-rhoda-1,2-dioxolanes (κ²C¹,O²-2-peroxyethyl rhodium complexes) have now been prepared by oxygenation of solid [(N₄-ligand)Rh^I(ethene)]PF₆ (see scheme) with air. This process leads to stable isomeric 3-rhoda-1,2-dioxolanes A and B. Upon substitution of PF₆⁻ by BPh₄⁻ only isomer B is obtained. The X-ray structure of isomer B is presented.

The three most important “superbase” anionic building blocks are contained in the striking decalithium aggregate in the structure of which a single lithium atom is surrounded solely by an amide, an alkoxide, and a carbanion (see picture).

A series of bowls separated by hour-glass-shaped channels characterizes the structure of the undulating two-dimensional coordination polymer (see picture) that is prepared from a nanoscale secondary building unit (nSBU), which is formed by four square metal(II)carboxylate SBUs that have 1,3-benzenedicarboxylate units as 120° spacers.

Small rhombihexahedra and small cubicuboctahedra (see picture), namely faceted polyhedra, form the basis of two novel low-density framework solids that are afforded by the self-assembly of molecular squares only or molecular squares and triangles, respectively.

A cage-type receptor binds an NH₄⁺ ion by cation–π interactions and hydrogen bonding (see picture) with high sensitivity and selectivity, comparable or even superior to those of the natural antibiotic nonactin over a wide pH range. The high performance, low cost, and easy synthesis may offer practical applications for this receptor as an ammonium ion sensor.

Reminiscent of Russian Matrioshka dolls, tetraazamacrocycles (1,4,7,10-tetraazacyclododecane (cyclen) and 1 , 4 , 8 , 11 - tetraazacyclotetradecane (cyclam)) and their transition metal complexes are encapsulated in the cavity of cucurbit[8]uril (CB[8]). The X-ray crystal structure of the [Cu(cyclen)] in CB[8] complex (see picture; copper: green, oxygen: red, nitrogen: blue, carbon: gray) reveals a five-coordinate Cu^II center in a square-pyramidal environment with a water molecule bound to the axial position.

Exhaustive fluorination of deca-B-methyl-para-carborane (1) furnishes perfluoro-deca-B-methyl-para-carborane (2) almost quantitatively [Eq. (1)]. Compound 2 represents the first neutral perfluorinated sphere mimicking a “Teflon ball”. The properties of 2 as well as its X-ray structure are discussed.

Modular units of Li₂[B-octaiodo-12-mercuracarborand-4⋅I₂] (Li₂[(HgC₂B₁₀H₈I₂)₄⋅I₂]) self-assemble forming infinite one-dimensional chains and microporous channels in the solid state (see picture). Self-assembly is directed by a unique B−I⋅⋅⋅Li⋅⋅⋅I−B intermolecular interaction involving electron-rich B–I vertices and electron-deficient lithium cations.

UV irradiation was found to accelerate the rate of gas incorporation into wide-bandgap ionic crystals and thus the rate of stoichiometry change. Up to now, this could only be achieved by changing the temperature, the dopant concentration, or adding catalytic coatings. The stoichiometry strongly affects the electrical conductivity of the crystal. The investigation of this effect provides valuable information on the mechanism of the surface reaction as well as offering new possible applications.

A sequence of reduction, deoxygenation, and coupling steps results in a remarkable reaction, which represents an important new method for the synthesis of 1,2-diamines. The vicinal diamines are formed by the facile coupling of aromatic amides in the presence of titanocene catalysts and PhMeSiH₂ (see scheme).

On pyrrole! The pyrrole-based corrole ligands can offer an alternative to porphyrin systems. The manganese corroles 1–4 are readily synthesized, undergo metal- not ligand-based redox chemistry, and 4 in particular shows impressive catalytic activity in the oxygenation of styrene with iodosylbenzene.

Nanoparticles of Fe₃O₄coated with 2-carboxyterthiophene (TTP-COOH) self-assemble through π–π interactions to form uniform transparent microspheres (see schematic representation). The interaction between individual particles is relatively weak and the spherical aggregates can be destroyed by sonication to leave the monodispersed nanoparticles.

Conjuring with conjugation: catalysis by ruthenium–allenylidene complexes has been observed for the conversion of tin hydrides into distannanes and dihydrogen (see scheme). Alkyne or alkene groups (R) in conjugation with an aromatic ring are required for catalytic activity, providing an unusual example of control of metal-centered reactivity by a remote substituent.

A zirconocene double act: The course of zirconocene-mediated macrocyclization is controlled by templating effects. In macrocyclizations of bipyridine-containing diynes, the zirconocene reagent [Cp₂Zr(py)(Me₃SiC≡SiMe₃)] (1; py=pyridine) acts as both coupling and templating agent. Thus, by controlling the stoichiometry, dimeric (see scheme) or trimeric macrocycles are obtained.

A multitude of natural product like molecules such as 2 and 3 can be readily obtained from hydroxyketoamide 1. The versatile 1 is derived, via the intermediate o-azaquinone 4, from the Dess–Martin periodinane oxidation of the corresponding anilide.

Getting spliced? Pre-mRNA splicing is catalyzed by the spliceosome, a complex assembly of proteins and RNA, which forms in an ordered fashion on the substrate. If one of the residues of the substrate is caged with a photolabile o-nitrobenzyl group, the splicing reaction can be transiently blocked, until subsequent initiation by photolysis of the complexes (see scheme). This RNA-caging approach effectively separates the spliceosome assembly from the catalytic reaction and allows the two processes to be studied independently.

Mimicking nature: The central mechanisms of living organisms depend on the formation of specific hydrogen bonds. Advances in the areas of catalysis and supramolecular chemistry have been applied here for the synthesis of a novel class of elastomeric polyolefins (see scheme) with properties dependent upon strong intermolecular hydrogen bonding.

KH and the two-phase system liquid ammonia/toluene provide the basis for a new method for the synthesis of organozirconium oxides such as [{(EtMe₄C₅)Zr}₆(μ₆-O)(μ₃- O)₈]⋅C₇H₈ (the central inorganic core of the cluster is shown). Altering the solvent to mesitylene has no influence on the core structure of the resulting organozirconium oxide.

A chair of gold: Analogous to cyclohexane, the trinuclear gold ring [Au₃(PAnP)₃][ClO₄]₃ (PAnP=9,10-bis(diphenylphosphino)anthracene) shows a chair conformation and diastereotopic axial and equatorial phenyl rings. Variable temperature and 2D EXSY NMR studies reveal that the gold ring undergoes cyclohexane-like ring inversion (enantiomerization) in solution. In addition, the gold ring exhibits intense excimeric emission at room temperature. — = anthracene ring system in PAnP, ○ = ClO₄⁻.

A supramolecular recognition interface is formed through the self-assembly of cyclic D,L-peptides. Phenyl–phenyl interactions direct the solid-state organization of dimeric peptide cyclo[(-L-Phe-D-^MeN-Ala-L-hPhe-D-^MeN-Ala)₂] (1) by forming clusters of edge-to-face contacts between dimers (shown left), which suggests that these peptide scaffolds may be useful subunits for crystal engineering.

Pores for thought: A new extra large germanate zeolite-type structure has been synthesized by using high-charge multiamine as a template in a pseudo-aqueous system (DMF/H₂O). The novel zeolite-type germanate with low framework density (11.1) has a 24- and 12-membered ring honeycomb array (see picture) with three-dimensional intersecting channels.

Direct borylation of C−H bonds in aromatic compounds can be achieved by using the efficient homogeneous catalyst precursor [RhCl(PiPr₃)₂(N₂)] and pinacolborane (HBpin; see scheme). High selectivity for the benzyl positions, observed for toluene, p-xylene, and mesitylene, was attributed to the formation of η³-benzyl intermediates.

A short Ga−N bond with double-bond character is displayed by the first monomeric imide of gallium, which was obtained by the reaction of [{HC(MeCDippN)₂}M:] (Dipp=2,6-iPr₂C₆H₃, M=Ga; see picture) with N₃-2,6-Trip₂C₆H₃ (Trip=2,4,6-iPr₃C₆H₂). The analogous aluminum (M=Al) compound is also readily available.

Silicate layers cross-linked by interlayer VO₅square pyramids form the basis of the three-dimensional frameworks of the structures of the title compounds (the structure of K₂(VO)(Si₄O₁₀)⋅H₂O is depicted). Alkali metal cations (•) and water molecules (○) occupy nonframework sites in these structures, which were synthesized hydrothermally.