Site-specific phenylation of pyridine catalyzed by phosphido-bridged ruthenium dimer complexes: a prototype for C-H arylation of electron-deficient heteroarenes

Direct and selective catalytic arylation of alpha-C-H bond in pyridine with iodobenzene was achieved in up to 70% yield. Phosphido-bridged bisruthenium complexes 6a and 6b arising from Ru3(CO)12 and PPh3 were identified as active catalysts. The formation of complexes 6a and 6b was investigated, a sequence of C-H and C-P bond cleavage, cluster fragmentation, and disproportionation was established, and the intermediate ruthenium complexes lying on this pathway were isolated and fully characterized.     

Selective C-arylation of free (NH)-heteroarenes via catalytic C-H bond functionalization

A new system for palladium-catalyzed arylation of a broad spectrum of free (NH)-heteroarenes has been developed (indole, pyrrole, pyrazole, 2-phenylimidazole, imidazole, benzimidazole, and purine). Remarkable selectivity has been achieved in the presence of MgO base, providing single C-arylation products, while no N-arylation and no bis-arylation products have been detected. In the case of free imidazole, exclusive C-4 arylation may be switched to exclusive 2-arylation by the addition of CuI to the Pd/Ph3P/MgO system. When free aryl-(NH)-azoles are desired, direct arylation eliminates three steps in comparison to standard methods, including N-protection, stoichiometric metalation or halogenation, and N-deprotection.     

Selective and catalytic arylation of N-phenylpyrrolidine: sp3 C-H bond functionalization in the absence of a directing group

We herein describe our studies on arylation of N-phenylpyrrolidine, which led to the development of a new transformation for the direct and selective arylation of sp3 C-H bonds in the absence of a directing group. In this method, Ru(H)2(CO)(PCy3)3 4 was used as the catalyst, and preliminary mechanistic studies suggested that Ru(Ph)(I)(CO)(PCy3)2 5 is the key intermediate of the catalytic cycle. A large kinetic isotope effect (kH/kD = 5.4) was observed, which supports the proposal that C-H bond metalation is the slow step. Preliminary examination of the substrate scope showed that in addition to N-phenylpyrrolidine, N-methyl- and N-benzylpyrrolidine, as well as N-benzoylpyrrolidine, were arylated under the reaction conditions.     

Iboga Inspired N-Indolylethyl-Substituted Isoquinuclidines as a Bioactive Scaffold: Chemoenzymatic Synthesis and Characterization as GDNF Releasers and Antitrypanosoma Agents

The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N-indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels–Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC₅₀ 1–8 μM) and two of them (compounds 6 and 14) showed a good selectivity index.     

ESR-Linienbreite der Ionen der Eisengruppe in Lösungen

Electron spin resonance linewidths of ions belonging to the first transition group with quenched orbital angular momentum are calculated using a modified relaxationmatrix theory including third and fourth order perturbation terms. We base our calculation on a Hamiltonian, which depends on electron spin, nuclear spin, orbital angular momentum, rotation of the whole complex, and vibration of the ligands. Quadrupol effects, intermolecular electron-electron and electron-nucleus interactions are neglected. The results show that the well-known formula of the transverse relaxation time derived by using the spin-Hamiltonian is correct, if first the contribution of the rotational spin orbit process is taken in consideration and second the rotational correlation timeτ _c is replaced byτ _v =(1/τ _c +1/τ(0))^?1. 1/τ(0) describes the linewidth of the lowest energy value of the electrostatic energy of unpaired electrons in the ligand field. The linewidth arises from the normal modes of the complex; the calculation gives τ(0)=l0^?11...10^?12 sec.     

Näherungsverfahren zur Auswertung von ESR-Spektren

In general the determination of the line-shape data of electron spin resonance of free radicals is only possible by using a computer. Therefore the superposition of Lorentzian is often replaced by a single over-all Lorentzian line. However, the disadvantage of this simplification is the impossibility to explain the variation of the line-shape factor. Formulae are given for the approximative determination of the line-shape data, which explain the variation of both the linewidth and the line-shape factor. To test the approximation, a comparison between the exact computed parameters of the tetracyanoethylene anion, given byGendell, Freed andFraenkel, and our calculation have been made.     

Two-photon induced uncaging of a reactive intermediate. Multiphoton in situ detection of a potentially valuable label for biological applications

[reaction: see text] Two-photon induced Wolff rearrangement of a terphenyl diazoketone 1 was achieved by using focused laser pulses of 532 nm from a Q-switched Nd:YAG laser. The nonfluorescent terphenyl diazoketone 1 was transformed into a fluorescent ester derivative 4, which can be detected in situ using the focused laser pulses at 532 nm. Laser power dependence studies show that the Wolff rearrangement is induced by two-photon absorption of the terphenyl diazoketone 1, but suggests that more than two photons of 532 nm are involved (a multiphoton process) in excitation of the ester derivative 4.     

Feedback cooling of a single neutral atom

We demonstrate feedback cooling of the motion of a single rubidium atom trapped in a high-finesse optical resonator to a temperature of about 160 μK. Time-dependent transmission and intensity-correlation measurements prove the reduction of the atomic position uncertainty. The feedback increases the 1/e storage time into the 1 s regime, 30 times longer than without feedback. Feedback cooling therefore rivals state-of-the-art laser cooling, but with the advantages that it requires less optical access and exhibits less optical pumping.     

Catalytic C-H arylation of SEM-protected azoles with palladium complexes of NHCs and phosphines

[reaction: see text] The synthesis and catalytic evaluation of palladium complexes containing imidazolyl carbene ligand of varying steric and electronic properties is reported. These complexes catalyze the efficient C-H arylation of SEM-protected azole heteroarenes and thus provide a good method for preparation of a wide range of arylated free (NH)-azoles including pyrroles, indoles, imidazoles, and imidazo[1,2-a]pyridines. The reaction is operationally simple; the complexes are insensitive to moisture.