The addition of alkyllithium reagents to trans-cyclooctene. The facile elimination of lithium hydride in the cyclooctyl ring

The addition of s-butyllithium and t-butyllithium to trans-cyclooctene has been shown to occur very readily. The facile elimination of lithium hydride from s-cyclooctyllithium compounds affording cyclooctenes is also reported.     

Molecular conformation of cyclenes: Part VI. MINDO/2' study of 1,3-cycloheptadiene,cis- and trans-cyclooctene

Quantum mechanical calculations indicate that the most stable conformation for 1,3-cycloheptadiene is a C_s semi-planar form, for trans-cyclooctene a C₂ twist form and for cis-cyclooctene a form without symmetry. An equilibrium between two C₁ forms and the C_s form can be suggested as a consequence of the negligible rotational barrier in 1,3-cycloheptadiene; no obviously preferred conformations exist in cis-cyclooctene, where the molecule is quite flexible. Theoretical results are consistent with the experimental data available.     

Force-field calculations for some unsaturated cyclic hydrocarbons

Boyd's iterative force-field computer program, with modified parameters, has been used to calculate strain energies in the following molecules: trans-cyclooctene, cyclohexene, melhylenecyclohexane, 1,3,5- and 1,3,6-cyclooctatriene, and cyclononyne. Both static and dynamic aspects of the conformational properties of these molecules have been investigated in detail, and the results are discussed in conjunction with extant experimental data and previous force-field calculations.     

1,3-dipolar cycloadditions of aromatic azoxy compounds to strained cyclo-alkenes

The 1,2,3-oxadiazolidines resulting from the addition of 4,4′-dicyano-azoxybenzene to trans-cyclooctene or cis, trans-cycloocta-1,5-diene are not stable, bu suffer 1,3-dipolar cycloreversion to give an azomethine imine; this intermediate is either captured by a second molecule of the strained cycloalkene to give 1:2 adducts in high yields or it tautomerizes to an enehydrazine. 4,4′-Dinitroazoxybenzene and benzo[c]cinnoline N-oxide react analogously.     

Hydroxybromierung und Methoxybromierung von (Z)-Cycloocten

In addition totrans-2-bromocyclooctanol andtrans-1,2-dibromocyclooctane,cis-4-bromocyclooctanol,cis-1,4-dibromocyclooctane,trans-1,4-dibromocyclooctane, and (Z)-5-bromocyclooctene are obtained, when (Z)-cyclooctene is treated with N-bromosuccinimide in the presence of water. Similarly the methoxybromination of (Z)-cyclooctene gives transanular products.     

Efficient 18F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells

A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with ¹⁸F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.     

Ab initio calculation of electronic circular dichroism fortrans-cyclooctene using London atomic orbitals

Summary The second-quantization magnetic dipole operator that arises when London atomic orbitals are used as basis functions is derived. In atomic units, the magnetic dipole operator is defined as the negative of the first derivative of the electronic Hamiltonian containing the interaction with the external magnetic field. It is shown that for finite basis sets, the gauge origin dependence of the resulting magnetic dipole operator is analogous to that of the exact operator, and that the derived operator converges to the exact operator in the limit of a complete basis set. It is also demonstrated that the length expression for the rotatory strength in linear response calculations gives gauge-origin-independent results. Sample calculations ontrans-cyclooctene and its fragments are presented. Compared to conventional orbitals, the basis set convergence of the rotatory strengths calculated in the length form using London atomic orbitals is favourable. The rotatory strength calculated fortrans-cyclooctene agrees nicely with the corresponding experimental circular dichroism spectrum, but the spectra for the fragment molecules show little resemblance with that oftrans-cyclooctene.Dedicated to Prof. Jan Linderberg     

IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications

The pretargeting strategy has recently emerged in order to overcome the limitations of direct targeting, mainly in the field of radioimmunotherapy (RIT). This strategy is directly dependent on chemical reactions, namely bioorthogonal reactions, which have been developed for their ability to occur under physiological conditions. The Staudinger ligation, the copper catalyzed azide-alkyne cycloaddition (CuAAC) and the strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC) were the first bioorthogonal reactions introduced in the literature. However, due to their incomplete biocompatibility and slow kinetics, the inverse-electron demand Diels-Alder (IEDDA) reaction was advanced in 2008 by Blackman et al. as an optimal bioorthogonal reaction. The IEDDA is the fastest bioorthogonal reaction known so far. Its biocompatibility and ideal kinetics are very appealing for pretargeting applications. The use of a trans-cyclooctene (TCO) and a tetrazine (Tz) in the reaction encouraged researchers to study them deeply. It was found that both reagents are sensitive to acidic or basic conditions. Furthermore, TCO is photosensitive and can be isomerized to its cis-conformation via a radical catalyzed reaction. Unfortunately, the cis-conformer is significantly less reactive toward tetrazine than the trans-conformation. Therefore, extensive research has been carried out to optimize both click reagents and to employ the IEDDA bioorthogonal reaction in biomedical applications.     

Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part VI: Octakis (2,3,6-tri-O-pentyl)-γ-cyclodextrin

Perpentylated γ-cyclodextrin is a very hydrophobic liquid which exhibits enantioselectivity toward a number of non-polar chiral substrates including the saturated hydrocarbons cis- and trans-pinane, β-chiral olefins, iron(O) tricarbonyl complexes of prochiral olefins and 3,3,8,8-tetramethyl-trans-cyclooctene, a compound with planar chirality.     

Ethyl acetate: Gas phase infrared spectra,ab initio calculation of structure and vibrational frequencies and assignment

Gas phase IR spectroscopic measurements of ethyl acetate are reported and the vibrational bands are assigned for the trans—trans and trans—gauche conformers. An extensive ab initio calculation has been carried out for both the conformers to obtain molecular structure, barrier heights, vibrational frequencies, force field, IR intensities and multipole moments. Theoretical calculations are of great help for assignment of the free molecule frequencies, which often show deviation from the condensed phase values.     

Reaktionen von (E)-Cycloocten mitN-Bromsuccinimid in Gegenwart von Wasser oder Methanol

The reactions of (E)-cyclooctene withN-bromosuccinimide in the presence of water or methanol are described. Major products of the hydroxybromination aretrans-4-bromocyclooctanol as a product of intermediary transanular hydride migration, and two ring contracted bromohydrines. The methoxybromination has been found to occur similarly.

6. Mitt.:G. Haufe undM. Mühlstädt, Z. Chem., im Druck.     

Cyclooctene epoxidation with H2O2 and single crystal X-ray determined crystal structures of new molybdenum and tungsten catalysts bearing the hydrophilic ligand hydroxymethyldiphenylphosphine oxide

The dioxo molybdenum and tungsten complexes MoO₂Cl₂(OPPh₂CH₂OH)₂ and WO₂Cl₂(OPPh₂CH₂OH)₂ have been synthesized and characterized by FT-IR, ¹H and ³¹P NMR. Their structures, as determined by single crystal X-ray diffraction analysis, reveal distorted octahedral geometries with cis terminal oxygen atoms, trans Cl ligands and that the hydroxymethyldiphenylphosphine oxide ligands coordinate through the oxygen atom bonded to the P atom. Both of the compounds are studied as catalysts for the epoxidation of cis-cyclooctene in the presence of hydrogen peroxide as a source of oxygen. Both complexes showed good activity and very high selectivity for the formation of cyclooctene oxide.     

Molecular conformations of methyl formate and methyl vinyl ether from ab initio molecular orbital calculations

Ab initio molecular orbital theory with minimal and extended basis sets and a flexible rotor geometric model has been used to investigate the rotational potential surfaces of methyl formate and methyl vinyl ether. For both molecules, the most stable structures (IA and IIA, respectively) are planar cis; additional potential minima are found which correspond to planar trans structures (IB and IIB). The latter lie respectively about 4—8 and 1—2 kcal mol^?1 above the corresponding cis rotational isomers. Methyl rotational barriers have been determined for cis and trans structures of each molecule. For trans methyl formate, there is a slight but unexpected preference for an eclipsed arrangement of the methyl group.     

Preparation and characterization of trans-RhCl(CO)(TPPTS)2-intercalated layered double hydroxides

trans-RhCl(CO)(TPPTS)₂ (TPPTS=tris(m-sulfonatophenyl)phosphine) has been intercalated into Zn-Al layered double hydroxides (LDHs) by the method of ion exchange. The structure, composition and thermal stability of the composite material have been characterized by powder X-ray diffraction, Fourier transform infrared and ³¹P solid-state magic-angle spinning nuclear magnetic resonance spectroscopy, elemental analysis, thermogravimetry, and differential thermal analysis. The geometry of trans-RhCl(CO)(TPPTS)₂ was fully optimized using the PM3 semiempirical molecular orbital method, and a schematic model for the intercalated species has been proposed. The thermal stability of trans-RhCl(CO)(TPPTS)₂ is significantly enhanced by intercalation, which suggests that such materials may have prospective application as the basis of a supported catalyst system for the hydroformylation of higher olefins.     

Metal complexes of mercaptoamines—II: New assignment of the structure of bis(β-mercaptoethylamine)nickel(II) and related compounds

A cis-geometry was proposed for the green complex bis(β-mercaptoethylamine) nickel(II) on the basis of its reactivity, IR spectroscopy and orbital geometry considerations. The crystal and molecular structure of this complex has been determined by X-ray diffraction and shows that the complex has a trans geometry. The crystal structure consists of trans-NiL₂ molecules strongly linked through NH-S hydrogen bonds. Electronic and IR spectroscopy, and powder X-ray analysis are in agreement with the same trans geometry for the complexes bis(β-mercaptoethylamine)palladium(II) and bis-(γ-mercaptopropylamine)nickel(II). As a result of the new assignment of the structure of these complexes some concepts, such as its reactivity with nickel(II), are reconsidered.     

Reactivity of cyclooctene derived episulfonium ions toward nucleophiles and the course of sulfenyl halide addition to cyclooctene

The reactions of the stable S-methylepisutfonium ions derived from cis-cyclooctene with various nucleophiles were found to proceed mainly as the attack at a C atom of episulfonium ring in contrast to the previous data of Helmkamp et al.⁴ The course of the RSCI Ad_E-reaction with cyclooctene under the conditions of increased polarity corresponded to the formation of intermediates closely related to episulfonium ions. Transannular 1,5-hydride shift was observed for the reaction of 2,4-dinitrobensenesuilfenyl derivatives with cis-cyclooctene.     

[2+2] Cycloaddition of benzyne to cis,trans- and cis,cis-1,5-cyclooctadiene

The relative rates of formation of $\text{cis}$ and $\text{trans}$ [2+2]cycloadducts of benzyne to $\text{cis}$, $\text{trans}$- and $\text{cis}$, $\text{cis}$-1,5-cyclooctadiene, $\text{trans}$- and $\text{cis}$-cyclooctene are discussed and properties of the adducts (e.g., their unusual hydrogenation) are described.     

Polarized absorption spectroscopy of trans-azobenzene and trans-stilbene in stretched polyethylene films

The linear dichroism spectra of trans-azobenzene and trans-stilbene aligned in stretched polyethylene films are reported for the u.v.-vis region. On the basis of the results the u.v. transition moment directions with respect to the long molecular axis are determined. Infrared data indicate that trans-azobenzene has a non-planar geometry while trans-stilbene is more planar in the polyethylene matrix. The polarization direction of the nπ* transition in azobenzene is different from that of the first ππ* absorption band, which indicates a vibrational borrowing mechanism corresponding to a nonplanar geometry.     

Oxomolybdenum(VI) complexes with glycine bisphenol [O,N,O,O′] ligand: synthesis and catalytic studies

The oxomolybdenum(VI) complex [MoOCl(L)] with a tetradentate glycine bisphenol ligand (H₃L) was prepared by reaction of [MoO₂Cl₂(DMSO)₂] with a ligand precursor in hot toluene. The product was isolated in moderate yield as separable cis and trans isomers along with the third minor component, [MoO₂(HL)]. The solid-state structure of trans-[MoOCl(L)] was determined by X-ray diffraction. The ligand has tetradentate coordination through three oxygens and one nitrogen, which is located trans to the terminal oxo whereas the sixth coordination site is occupied by a chloride. Both cis and trans isomers of [MoOCl(L)] are active catalysts for epoxidation of cis-cyclooctene and sulfoxidation of tolyl methyl sulfide. The cis isomer gave higher activity in epoxidation and sulfoxidation reactions at room temperature than the trans isomer but they performed identically at 50?°C.