Angewandte Chemie International Edition

The history of multicomponent reactions with isocyanides (IMCRs) and that of the isocyanides themselves took place in three large, parallel waves. The first wave was the constituting one, in which the isocyanides were discovered and their structure and identity recognized, some properties were examined, and limited preparative access was found. In the following years, research in this area was sporadic with only a few publications until the Italian Passerini discovered the self-named, first IMCR and investigated it for many years (the second wave). It grew silent again for many decades until a general and good appproach to the class of the isocyanides was found. In this third wave, the largest so far, which may not even have reached its climax yet, the Ugi reaction and many new IMCRs, many biologically active natural compounds, new heterocycle syntheses with isocyanides, and other important synthetic applications of isocyanides were described. Finally, the immense advantages of the IMCRs in drug research were recognized.

No longer just an imaging technique: in the last couple of years force microscopy has become a versatile tool for single-molecule spectroscopy. Examples of its use (shown schematically) as well as the investigation of bond rupture in single ligand–receptor couples and the elasticity of individual polymers are described.

Finally—the line-resolved infrared spectrum of the methonium ion recorded! But what do more than 900 vibrational absorptions mean to the experimental and theoretical chemist? How appropriate is the notion of “structure” for CH₅⁺ (see picture)?

In the C−F bond activation of perfluoroalkyl ligands under exceptionally mild conditions rhodium(III) and iridium(III) complexes perform a dual role. The metal not only provides a low-energy mechanism for C−F cleavage but also activates coordinated water or molecular hydrogen to provide a new route to hydrofluorocarbons (see scheme).

During adhesion events in eukaryotic cells polyvalent carbohydrate–carbohydrate recognition between Le^X oligosaccharides plays a role. Clustering was mimicked by a Lewis^X-based, synthetic, neutral calcium receptor 1. Two Lewis^X trisaccharides were covalently tethered and studied by NMR spectroscopy. In the presence of calcium, the two Le^X moieties assume a cross-shaped relative orientation. The conformation of the cluster was identified from additional NOE contacts.

A substantial fluorescence enhancement was observed when novel peptide nucleic acid (PNA) probes were hybridized with complementary DNA in homogeneous solution. For the synthesis of the doubly labeled PNA probes, a highly flexible strategy was developed (see scheme). All reactions, including the labeling steps, were performed on the solid phase. Bhoc=benzhydryloxycarbonyl; Boc=tBuOCO.

A chiroptical redox switch, the binaphthyl boron dipyrromethene conjugate (R)-1, is presented. The circular dichroism (CD) couplet of this compound at 501 nm disappears on reduction to the bisradical dianion and is completely restored on reoxidation. The CD effects of (R)-1 can be explained by quantum-chemical calculations.

Allosteric control of the activity of a low molecular weight catalyst by metal ions is demonstrated for the first time. In the trinuclear complex 1 two Cu²⁺ ions cooperate in the cleavage of the phosphodiester HPNP, while a third metal ion (M) is not directly involved in catalysis but is expected to create more or less reactive conformations of the catalyst. Relative reactivities for M=Pd^II, Ni^II, and Cu^II are 1:3:10.

An unusual type I polyketide defined in a unique hexacyclic skeleton was determined as the structure of hexacyclinic acid (1). The structure was elucidated by X-ray analysis in connection with chemical–spectroscopic methods, and the biosynthesis was explored through feeding experiments with ¹³C-labeled precursors. The compound was isolated by application of the OSMAC approach to Streptomyces cellulosae S 1013.

Treatment of the pure enantiomer 1 with methyllithium furnishes via cycloallene 2 its dimer 3 with high selectivity. In contrast, racemic 1 yielded only 5 % of 3 and 95 % of the cis isomer of 3. Thus, racemic 2 is an example of molecular recognition of remarkable selectivity.

Triple C−H bond activation in the reaction of [Cp(R₃PN)Ti(Me)₂] with AlMe₃ affords Ti-Al-C aggregates. These species 1 and 2 exist in equilibrium with AlMe₃, thus demonstrating a highly facile interconversion of carbide species with distorted tetrahedral and five-coordinate, pseudo-trigonal-bipyramidal geometries, respectively. R=iPr.

The existence of an equilibrium between the carbyne complex 1 a and the isomeric carbene 1 b (Ar_f=3,5-C₆H₃(CF₃)₂) has been confirmed by a variable-temperature NMR study. Compound 1 a is the first carbyneruthenium compound that has been structurally characterized.

The phototrigger function of phytochrome, the major photosensory pigment in plants, can be performed by a noncovalently bound linear tetrapyrrole (see picture). This tetrapyrrole was embedded into the chromophore pocket of the phytochrome apoprotein without covalent attachment (A), rather than being bound to cysteine Cys(321) as in the native chromoprotein (B).

A fully aromatic hexagonal ring with equal bond lengths of 1.372 Å (average) is found at the center of the fluorinated crown of C₆₀F₁₈⋅toluene. The X-ray crystal structure (see picture; ○=F) shows that one half of the fullerene cage is flattened and that the six-membered ring of sp²-hybridized carbon atoms is isolated from the rest of the molecular π system by a puckered fluorinated “belt” of sp³-hybridized carbon atoms.

A structure analogous to that of the rare mineral montregianite, a sodium yttrium silicate (see picture), is displayed by AV-5, the first example of a microporous framework cerium silicate. AV-5, which was synthesized under hydrothermal conditions from mixtures containing sodium silicate solution and Ce^III salts, has potential for applications in the field of optoelectronics.

Desaturation of the title acid, by an iron-containing desaturase enzyme, occurs in two steps as shown in the scheme. Deuterium labeling experiments show that tunneling of the hydrogen atom contributes to the transfer of hydrogen in the C9−H cleavage step.

Both physical and chemical forces play a role in the molecular recognition by a new synthetic receptor. The receptor host surrounds amine guests, while an inwardly directed “introverted” carboxy function (see picture) makes contact with the nitrogen atom. R¹=C₁₁H₂₃, R²=C₇H₁₅.

Copper(I)-induced template synthesis produces a linear rotaxane dimer capable of undergoing contraction and stretching motions of large amplitude under the action of a chemical stimulus (see scheme). The process is reminiscent of those observed in natural muscles.

The dihedral angles of Si-Si-Si-Si frameworks were controlled to ∼10°(S), 180°(A), and ∼120°(E) by the use of the syn- and anti-disilane units that are configurationally constrained by two pentamethylene tethers. The UV absorption spectra of the tetrasilanes (see picture) were found to be consistent with the new explanation proposed by Michl and co-workers for the UV absorption of polysilane compounds.

β-Substituted acrylates with high diastereomeric excess can be prepared by coupling optically active acetylenic ester titanium alkoxide complexes with aldehydes [Eq. (1); El=electrophile]. This reaction represents an asymmetric transformation complementary to the Baylis–Hillman reaction.

Detection and quantification of material synthesized on a single resin bead is now possible using standard UV spectroscopy and mass spectrometry by the introduction of an analytical construct (A) before the linker (L2; see scheme). Cleavage of the analytical fragment is achieved by the introduction of another, orthogonal, linker (L1) that releases the labeled substrate into solution.

Switching the charge of metallocene receptors (M=Fe, Co) on or off controls their binding strength with glutaric acid (GA; see scheme). These receptors containing amidopyridine units bind glutaric acid through hydrogen-bonding interactions.

Transfer of crystallinity from dihydrogen- to covalent-bonded networks is possible! This concept was demonstrated by the single-phase solid-state decomposition of NaBH₄⋅THEC (THEC=N,N′,N″,N′′′-tetrakis-(2-hydroxyethyl)cyclen), in which self-assembly into dihydrogen-bonded closed-looped dimers (see picture) minimizes the unit-cell shrinkage accompanying the OH⋅⋅⋅HB to O−B conversion.

Brønsted acid sites are created on the surfaces of oxides such as silica gel and zirconia by reaction with SO₃. This is shown by NMR studies of adsorbed probe molecules and by theoretical calculations. In the case of silica gel, the resulting site is a hydrogen sulfate ester as shown in the figure.

One- or three-dimensional structures of the lanthanide–transition metal coordination polymers are prepared through hydrothermal reactions. The reaction of Gd₂O₃, 2,5-pyridinedicarboxylic acid (H₂pydc), and either Cu(OAc)₂ or CuO resulted in [{Gd₂Cu₃(pydc)₆(H₂O)₁₂}⋅4 H₂O]_n (1) or [{Gd₄Cu₂(pydc)₈(H₂O)₁₂}⋅4 H₂O]_n (2), respectively, depending upon the coordination of the pydc ligand. The picture shows the three-dimensional wavelike structure of 2.

A four-center bond depicting ligand–ligand interactions was found to be critical for the stabilization of the planar structures of the tetracoordinate molecules containing Si and Ge centers (SiAl₄⁻ and GeAl₄⁻). Both the anionic and neutral forms were observed and characterized (the structures of the Si molecules are shown). These species violate the conventional expectation of tetrahedral structures for tetracoordinate Si and Ge species and extend our concept of the range of chemical bonds that Si and Ge centers can form in nonstoichiometric molecules.

“Onions with spaces” are the new type of multi-lamella spherical vesicles formed by block copolymers. This morphology consists of concentric vesicles with uniform spaces between the vesicle walls (see picture). Multi-lamella “solid onions” in which there is no spacing between the vesicle walls were also prepared and the factors governing the formation of these new species investigated.

An extended array of clusters held together by hydrogen bonds is exhibited by (cryptNa)₂[Mo₆Cl₈(OC₆H₄CONH₂)₆] (1, structure shown; crypt=cryptand). Depending on the crystallization conditions, 1 can adopt two different packing structures with different channel sizes between the layers. The structures and photophysical properties of 1 are discussed.

Solid-phase synthesis of polyketide-type sequences, such as 1, can be achieved efficiently by iterative, boron-mediated, aldol reactions of chiral ketones 2 with a polystyrene-supported aldehyde 3. Combinatorial variation of the chain extension units, and the stereochemistry of the aldol and reduction steps, leads to the expansion of polyketide molecular diversity. PMB=p-MeOC₆H₄CH₂.

The first heterocumulene featuring both an ylide bond and a π double bond has been isolated. This highly functionalized molecule appears to be a very versatile and selective reagent (see scheme).

The chelation mode selected by the anion of 4,5-bis(diphenylphosphinoyl)-1,2,3-triazole, which is the prototype of a powerful and very stable novel ligand class, is dependent on the metal ion to be coordinated (see scheme).