Angewandte Chemie International Edition

Atomic-scale dynamics as reactions unfold and pass through transition states is the focus of the field of femtochemistry. With femtosecond time resolution structures can be “frozen” far from equilibrium and prior to their vibrational and rotational motions that lead to reaction. Hence the dynamics of the chemical bond can now be observed and studied, addressing the fundamentals: how the energy put into a reactant molecule redistributes among the different degrees of freedom, and how fast this happens, the speeds of the chemical changes connecting individual quantum states in the reactants and products, and the detailed nuclear motions that chart the reaction through its transition states, and how rapid these motions are. Femtochemistry is making an impact in all areas of chemistry and adjacent sciences.

Homo- and heterocoupling reactions of acetylenes [Eq. (a) and (b), respectively] represent some of the most powerful methods for the construction of carbon frameworks in contemporary chemistry. Their power is illustrated in natural product synthesis as well as the targeted synthesis of molecular receptors and all-carbon and carbon-rich molecules.

Metal–metal bonds between transition metal centers with extremely different electronic properties are highly polar and highly reactive. Our understanding of such structural units in polynuclear complexes has advanced significantly and provides the foundation for the exploration of their cooperative reactivity with organic molecules, for example, with regard to applications in catalysis. The picture shows two isosurfaces of the electron localization function of 1.

The molecular parameters of poly(3-alkylthiophene)s 1 (R=C₆H₁₃, C₁₂H₂₅), coupled head-to-tail, have been observed by scanning tunneling microscopy of their two-dimensional crystals. Polymer folds and conformations at a submolecular resolution is clearly presented (see image for 1, R=C₁₂H₂₅), as is a greater electronic coupling from these “molecular wires” stacked parallel in a second layer.

Individual tautomers are selected for complex formation with metal ions of different ionic radius, which induce bias in the typical target-driven dynamic combinatorial virtual libraries of tautomeric systems. The macrocyclic tautomers are made of cores consisting of cis-1,5-dioxa-3,7-diazadecalin (DODAD) or cis-3,7-dioxa-1,5-azadecalin (DADOD) and the corresponding Schiff bases, bridged by various ligating spacers. Thus, [1+1], [2+2] (see picture), and [3+3] manifolds are formed from (not all necessarily or substantially extant) macrocycles in dynamic tauomeric equlibrium.

Ten defined chiral centers are present in the [15]metallacrown-5 complex that is assembled in a one-step reaction from L-tyrosinehydroxamic acid, Cu^II, and Gd^III. Nitrate ions bind selectively to this complex in a cavity of dimension 776 ų, while chloride binds to the outer face (see picture).

A mimic of monooxygenase enzymes: An artificial cytochrome P-450 with four cyclodextrins linked to a manganese/porphyrin complex can insert an oxygen atom into unactivated C−H bonds with catalytic turnovers (see picture). Hydroxylation of a doubly bound diester of androstane-3,17-diol at C-6 is possible; further oxidation of the triply bound triester of this product occurs at C-9.

Volatile species and large gas atoms, such as xenon, can diffuse into the aromatic nanochannels of a solid comprising tris(o-phenylenedioxy)cyclophosphazene molecules held together by weak interactions. Continuous-flow laser-polarized ¹²⁹Xe NMR spectroscopy shows an anisotropic signal from the xenon atoms inside the crystals as soon as 200 ms after contact of the polarized gas with the sample. The xenon chemical shift anisotropy is concentration dependent (see picture) and undergoes a sign inversion as a result of the change of the symmetry of electron cloud.

Cucurbituril is used as the molecular “bead” for the synthesis of the first three-dimensional polyrotaxane network, which shows an inclined α-polonium topology. The novel solid-state interlocked structure is made up of binulcear Tb³⁺ centers and pseudorotaxane units containing cucurbituril “beads” threaded on a “string” with 3-phenylcarboxylate terminals (shown schematically).

Tailored microcavities with good size and shape selectivity can be created within long-chain molecular layers assembled in ordered nanoporous channels by using a molecular imprinting technique. The microcavities can be opened or closed by changing the conformations of the molecular chains (see picture).

The controlled construction of a microporous/macroporous materials from diatomaceous earth and a high silica zeolite by a simple method is reported. The picture shows scanning electron microscopy images of the material at two scales (left and center) and the arrangement of the zeolite crystals precipitated onto it (right). These materials have numerous potential applications in the areas of ion exchange, filtration, and catalysis.

The minimal structure required to inhibit the dimerization of HIV-1 protease has been determined by removing residues from the N termini of the peptides in 1, a known inhibitor (K_i=220±10 nM) that was obtained by cross-linking the N termini of interfacial peptides of HIV protease, and then replacing the Trp-OH residue with Phe-NH₂. Molecular modeling of the resulting structure led to 2, which inhibits HIV-1 protease through a dissociative mechanism and is an ideal starting point for identifying more potent agents.

A triple-domino reaction involving a Grignard addition, an oxy-Cope rearrangement, and a Dieckmann cyclization provides olefin-containing polycyclic bridgehead compounds from simple vinylated β-ketoesters [Eq. (1)]. This general methodology allows the quick preparation of ring systems not easily accessed by other methods.

The combination of two important organizational principles, that is surfactant monolayer assembly and the triazinetriamine–triazinetrione hydrogen-bonding molecular ribbon, produces a hybrid assembly which is used as a novel template to control the orientation and morphology in the crystallization of calcium carbonate (see picture).

Local attractions characterize the interanionic O−H⋅⋅⋅O hydrogen bonds in crystalline potassium hydrogenoxalate. This is the conclusion of theoretical and experimental studies on the electron density distribution. This contradicts a recent claim that such interactions are electrostatically repulsive. The picture shows the Laplacian function of the electron density in the region of the hydrogen bond.

The radical-induced cyclization of 1,2-bis(phosphanyl)ethane and diallylphenylphosphane coordinated to a (pentamethylcyclopentadienyl)iron(II) template gives the first ten-membered triphosphorus macrocycle with three inequivalent phosphorus centers [Eq. (1); AIBN=azobisisobutyronitrile].

In an aprotic solvent, dimethylformamide, a coupling reaction between an α,β-unsaturated ketone and an aldehyde is achieved with chromium(II) chloride. An intermolecular aldol reaction and an intramolecular cyclization proceed sequentially to give cis-2-hydroxyalkyl-substituted cyclopropanol stereoselectively [Eq. (a)].

A remarkable bicyclic acetal template effect is responsible for the complete 1,2-trans stereoselectivity achieved in Lewis acid promoted allylations of 1,2-O-isopropylidene-protected furanosides [Eq. (1)]. This stereoselectivity occurs regardless of the other substituents on the tetrahydrofuran ring. The bicyclic acetal acts as a basic, stable anomeric protecting group, and activates the carbohydrate anomeric position and directs the stereochemical outcome of the substitution reaction at this center.

Alternate stacking of single hexagonal perovskite (111) layers (La₂MnO₆) and “Ca₂O” layers is present in the hexagonal perovskite intergrowth compound La₂Ca₂MnO₇. Comparison with the Ruddlesden–Popper phases (ABO₃)_nAO suggests that La₂Ca₂MnO₇ might be the first member (n=1) of a family of hexagonal perovskite intergrowth compounds of the formula (La_n+1Mn_nO_3n+3)(Ca₂O).

The chromoprotein enediyne antibiotic kedarcidin has a structurally complex and highly reactive chromophore component. An enantioselective synthesis of compound 1, which contains the full functionality of the chromophore core, is described. The key step in the synthetic route involves low-temperature halogen–lithium exchange initiated transannular cyclization of the macrocyclic vinyl bromide 2. TBS=tert-butyldimethylsilyl.

ortho-Sulfinyl-substituted benzyllithium reagents react with aldehydes and ketones to afford, after desulfurization with Raney-Nickel, stereoselective access to benzylic stereocenters [Eq. (1)]. This is the first efficient asymmetric 1,4-induction with mediation by a sulfoxide group. LDA=lithium diisopropylamide; Tol=tolyl; TIPS=triisopropylsilyl.

A heterogeneous catalyst prepared in water is, clearly, a cleaner one that leads to cleaner syntheses. La₂CuO₄ formed in supercritical water is produced more quickly, has a higher surface area, and a greater activity towards CO oxidation than the corresponding materials prepared by “traditional” ceramic synthesis. The method could feasibly be scaled up or applied to other solid-state products.

The covalent attachment of molecular species to the silicon surface by an organic radical based C−C bond formation reaction has been demonstrated with the dimerization of adsorbed furan on Si(111)-(7×7). This facile reaction is attributed to the recombination of pairs of adjacent mono-σ complexes at low temperature (see the reaction scheme).

An octanuclear supramolecular assembly comprising La ions in a square antiprismatic array is found in [La₈L]. The eight nine-coordinate lanthanum centers are coordinated here by eight rigid C₃-symmetric pyrazolone ligands L¹ to give an extraordinary ring architecture (see picture).

Integral and differential cross sections for the reaction H + D₂ → HD(v′=3,j′) + D at a collision energy of 1.64 eV have been measured and compared with quasiclassical trajectory calculations. The low j′ states of the HD product show strong forward scattering (see picture for j′=0), which is attributed to the formation of a short-lived quasibound collision complex.

The construction of quaternary stereocenters with 95–99% ee at ambient temperatures can be achieved by a copper-catalyzed Michael reaction with the application of α-amino acid amides as chiral auxiliaries [Eq. (1)]. These amides can be obtained in a few steps from the α-amino acids with standard transformations and, after the Michael reaction, they can be quantitatively recovered. Exclusion of water and oxygen is not necessary.

The key step in the biosynthesis of (R)-β-dopa in the mushroom Cortinarius violaceus is the intramolecular transfer of the amino group in L-tyrosine (see picture). 2,3-Aminomutases have not previously been reported in fungi.

Tetraatomic chiral molecules, such as S₂FCl, S₂BrF, and S₂BrCl, can enantiomerize by completely chiral paths because two of the atoms are of the same chemical element and exchange roles.

High 1,3-stereoinduction is obtained in the chelation-controlled trapping of acyclic radicals, which are of interest as models for radical polymerizations. The diastereoselectivity shows a remarkable dependence on the steric effect of the substituent R² and on the temperature: it is anti:syn=2:98 for R¹=Me, R²=tBu at −78 °C and 85:15 for R¹=Me, R²=Me at +40 °C [Eq. (1)].

To improve pharmacokinetic and -dynamic properties of peptidic, bioactive compounds they can be derivatized with carbohydrate building blocks. By incorporation into the peptidic backbone (see for example 1) the conformation of the pharmacophoric moieties can be influenced, while derivatization of side chains (see for example 2) mainly modifies the pharmacokinetic behavior.

Only eleven steps were needed to synthesize kuehneromycin A (1) which inhibits reverse transcriptase (see picture). Key steps are a new variant of the Baylis–Hillman reaction, an endo-selective intramolecular Diels–Alder reaction, and a new protocol for the Parikh–Doering oxidation. TBDPS=tert-butyldiphenylsilyl.

The first chemical proof is available to show that lactic acid bacteria, generally known for their limited metabolite spectrum, are able to produce antibiotics with a broad inhibitory spectrum. The new tetramic acid, reutericyclin (1), opens a new dimension in the discussion regarding the application of lactic acid bacteria in food preservation or for positively influencing the human intestinal microflora.

A rather unusual intermediate between a bent 2-phosphaallyl cation and a linear 2-phosphonio-allene is the structure of the cation [P(=NH)₂]⁺ according to ab initio calculations. The cation was obtained as the donor-stabilized salt 3 by reaction of 1 with two equivalents of the base p-dimethylaminopyridine (Do). Mes*=2,4,6-tBu₃C₆H₂.

The first stable organic hydride of a main group element of the sixth period (1) has been prepared by the simple reduction of the corresponding chloride precursor. Interestingly, compound 1 transforms into the dibismuthene 2 when heated [Eq. (1)].

β-elimination of α-halo-β-hydroxyesters 1 was achieved by using samarium diiodide as a metalating reagent, and afforded di- and trisubstituted (E)-α,β-unsaturated esters 2 with total steroselectivity. This method has also been extended to the corresponding disubstituted (E)-α,β-unsaturated amides.

The interaction of phospholipase A₂ (PLA₂) and other interfacially active enzymes with lipids is strongly influenced by properties such as phase structure and de-mixing phenomena. Lipid monolayers (see schematic representation) provide the opportunity to vary these properties in a systematic fashion and in combination with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) to quantify the enzyme activity. Chain-substituted diester and plasmalogen-analogous ether-ester-glycerophosphocholines were synthesized and their hydrolysis catalyzed by PLA₂ was investigated.

A short W−Ge triple bond and a η¹-bound Cp* substituent are characteristic of the germylyne complexes 2⋅toluene that are obtained from the reaction of 1 with the germylene complexes [Cp*GeX] (W−Ge 2.302(1) Å for X=Cl). Density functional calculations show that there are significant electronic differences between germylyne and carbyne ligands. X=Cl, Br, I; PP=Ph₂PCH₂CH₂PPh₂; Cp*=C₅Me₅.

A trimer of the phosphanylidene carbenoid, generated from Mes*P=CBr₂ with tert-butyllithium, is the novel route to the title compound. The 1,3,6-triphosphafulvene bears three 2,4,6-tri-tert-butylphenyl (Mes*) groups, which contribute to the kinetic stabilization. Coordination of this phosphorus-substituted fulvene derivative to pentacarbonyltungsten furnishes complex 1. The structure of the deep red prismatic crystals of 1 was established.

The rotation about two pivotal bonds in opposite directions and coupled with a methyl group is the cause for the fast photoisomerization of a pentadienal protonated Schiff base—and possibly of rhodopsin. This observation is the result of high-quality ab initio molecular dynamics simulations.