Thermische,nichtkatalysierte Cycloadditionen der Acrylverbindungen an Cycloheptatrien

The cycloaddition reactions of cycloheptatriene with acrylonitrile and methyl acrylate have been investigated in some detail. The exo ( 1 ) and endo ( 2 ) adducts resulting from the [2+2+2]-cycloaddition of acrylic components to the 2,5-positions of cycloheptatriene have been separated and the structures have been elucidated by NMR. The by-products are 7-endo-substitued derivatives of bicyclo[4,2,1]nona-2,4-diene ( 3 ), resulting from the formal [6+2]-cycloaddition to the 1,6-positions of cycloheptatriene. The mechanism of their formation is discussed. Irradiation (λ = 253,7 nm) of 3 in various solvents gave an almost quantitativ yield of [2+2]-cyclodimers of the 14 type. No intramolecular photocyclization of 3 to cyclobutenes 13a and/or 13b was observed.     

Enhancement of Host–Guest Interactions Using Rationally Designed Macrocyclic Boronic Esters with a Naphthalene Core

Efficient inclusion of electron‐deficient aromatic guest molecules in an organic solvent utilizing π‐stacking interactions was achieved by using two kinds of macrocyclic boronic esters, 1,4‐naph‐ [2+2] and 1,5‐naph‐ [2+2] , which were easily prepared by self‐assembly of 1,4‐naphthalenediboronic acid ( 3 ) or 1,5‐naphthalenediboronic acid ( 4 ) and racemic tetrol 1 with an indacene framework in a protic solvent. The X‐ray crystallographic analyses revealed that the tilt angles of the two naphthalene rings are different: that of 1,4‐naph‐ [2+2] is about 15° and that of 1,5‐naph‐ [2+2] is about 0°. Owing to the parallel alignment of two aromatic rings, 1,5‐naph ‐[2+2] has a much higher binding ability than 1,4‐naph‐ [2+2] . This knowledge could be useful for the design of the new host molecules in organic solvents.     

Dihydrobiphenylenes through Ruthenium‐Catalyzed [2+2+2] Cycloadditions of ortho‐Alkenylarylacetylenes with Alkynes

A new synthetic route to dihydrobiphenylenes has been developed. The process involves a mild Ru^II‐catalyzed [2+2+2] dimerization of ortho‐alkenylarylacetylenes or its more versatile variant, the Ru‐catalyzed [2+2+2] cycloaddition of ortho‐ethynylstyrenes with alkynes. Mechanistic aspects of this [2+2+2] cycloaddition are discussed.     

Control of the Stereochemical Course of [4+2] Cycloaddition during trans‐Decalin Formation by Fsa2‐Family Enzymes

Enzyme‐catalyzed [4+2] cycloaddition has been proposed to be a key transformation process in various natural product biosynthetic pathways. Recently Fsa2 was found to be involved in stereospecific trans‐decalin formation during the biosynthesis of equisetin, a potent HIV‐1 integrase inhibitor. To understand the mechanisms by which fsa2 determines the stereochemistry of reaction products, we sought an fsa2 homologue that is involved in trans‐decalin formation in the biosynthetic pathway of an enantiomerically opposite analogue, and we found phm7, which is involved in the biosynthesis of phomasetin. A decalin skeleton with an unnatural configuration was successfully constructed by gene replacement of phm7 with fsa2, thus demonstrating enzymatic control of all stereochemistry in the [4+2] cycloaddition. Our findings highlight enzyme‐catalyzed [4+2] cycloaddition as a stereochemically divergent step in natural product biosynthetic pathways and open new avenues for generating derivatives with different stereochemistry.     

DNA intercalating studies of [Ru(bpy)<Subscript>2</Subscript>HPIP]<Superscript>2+</Superscript> with intramolecular hydrogen bond ligand based on introduction of copper ion

The effects of copper ion on the interaction of [Ru(bpy)₂HPIP]²⁺(bpy = 2,2′-bipyridine, HPIP = 2-(2-hydroxyphenyl) imidazo [4,5-f] [1, 10] phenanthroline) with DNA have been investigated by electronic absorption spectroscopy and fluorescence spectroscopy. HPIP ligand of the complex with an intramolecular hydrogen bond can bind Cu²⁺ in the absence of DNA, as revealed by the absorbance and fluorescence decrease for [Ru(bpy)₂HPIP]²⁺. The resultant heterometallic complex binds to DNA via intercalation of HPIP into the DNA base pairs and its DNA-binding ability is stronger than [Ru(bpy)₂HPIP]²⁺ itself. The DNA bound [Ru(bpy)₂HPIP]²⁺ cannot bind Cu²⁺ at low Cu²⁺ concentration and the intramolecular hydrogen bond in HPIP is located inside the DNA helix. While the Cu²⁺ concentration is relative high, Cu²⁺ can quench the fluorescence of DNA bound [Ru(bpy)₂HPIP]²⁺. The quenching reason is proposed.     

Sensitivity of Positive Ion Mode Electrospray Ionization Mass Spectrometry in the Analysis of Thiol Metabolites

High signal intensities of glutathione (GSH), [GSH+H]⁺ (m/z 308), cysteine (CySH), [CySH+H]⁺ (m/z 122), and homocysteine (hCySH), [hCySH+H]⁺ (m/z 136), are observed in ESI MS with on‐line electrochemistry (EC). Dimers formed by H‐bonding, which are not electrochemical products, are detected as [2GSH+H]⁺ (m/z 615), [2CySH+H]⁺ (m/z 243) and [2hCySH+H]⁺ (m/z 271) together with disulfide dimers GSSG, CySSCy and hCySSCyh, [GSSG+H]⁺ (m/z 613), [CySSCy+H]⁺ (m/z 241) and [hCySSCyh+H]⁺ (m/z 269). When dopamine is present a thiol/dopamine quinone (DAQ) adduct is observed. Formation of this adduct is proposed to occur by an electrochemical mechanism during ESI. Catalysis of thiol oxidation and analysis of thiol mixtures is addressed.     

Improvement of selective d-cation binding by tetrathiacalix[4]arene hydrazides: synthesis and extraction properties

New de-tert-butyltetrathiacalix[4]arenes with acetylhydrazide substituents in cone and 1,3-alternate conformations have been synthesised with good yield by the hydrazinolysis of calix[4]arene ester derivatives. The recognition ability of synthesised macrocycles towards transition and alkali metals has been investigated by the picrate extraction method. The stoichiometry of complexes and the extraction constants have been determined. It has been found that tetrahydrazides do not extract alkali metal ions, but show an excellent affinity towards transition and heavy metal cations. The 1,3-alternate conformer of de-tert-butyltetrathiacalix[4]arene has revealed a remarkable selectivity for Ni²⁺ and Ag⁺ in the row of d-elements and for Cd²⁺ ion among the toxic heavy metals. The experimental data show that the removal of tert-butyl groups from tetrathiacalix[4]arene framework leads to the drastic improvement of extraction efficiency and selectivity of new tetrahydrazides.     

Substituent Effects on Fe+-Mediated [4+2] Cycloadditions in the Gas Phase

The Fe⁺-mediated [4+2] cycloaddition of dienes with alkynes has been examined by four-sector ion-beam and ion cyclotron resonance mass spectrometry. Prospects and limitations of this reaction were evaluated by investigating several Me-substituted ligands. Me Substitution at C(2) and C(3) of the diene, i.e., 2-methylbuta-1,3-diene, 2,3-dimethylbuta-1,3-diene, hardly disturbs the cycloaddition. Similarly, variation of the alkyne by use of propyne and but-2-yne does not affect the [4+2] cycloaddition step, but allows for H/D exchange processes prior to cyclization. In contrast, Me substituents in the terminal positions of the diene moiety (e.g., penta-1,3-diene, liexa-2,4-diene) induce side reactions, namely double-bond migration followed by [3+2] and [5+2] cycloadditions, up to almost complete suppression of the [4+2] cycloaddition for 2,4-dimethylhexa-2,4-diene. Similarly, alkynes with larger alkyl substituents (pent-1-yne, 3,3-dimethylbut-1-yne) suppress the [4 + 2] cycloaddition route. Stereochemical effects have been observed for the (E)- and (Z)-penta-1,3-diene ligands as well as for (E,E)- and (E,Z)-hexa-2,4-diene. A mechanistic explanation for the different behavior of the stereoisomers in the cyclization reaction is developed. Further, the regiochemical aspects operative in the systems ethoxyacetylene/pentadiene/Fe⁺ and ethoxyacetylcne/isoprene/Fe⁺ indicate that substituents avoid proximity.     

Diastereochemical differentiation of bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di‐exo‐, di‐endo‐ and trans‐2,3‐ and 2,5‐disubstituted trinorbornanediols, and di‐exo‐ and di‐endo‐ 2,3‐disubstituted camphanediols using different divalent transition metals (Co²⁺, Ni²⁺, Cu²⁺) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal‐coordinated complex ions were formed for cobalt and nickel: [2M+Met]²⁺, [3M+Met]²⁺, [M–H+Met]⁺, [2M–H+Met]⁺, [M+MetX]⁺, [2M+MetX]⁺ and [3M–H+Co]⁺, where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di‐exo‐2,3‐disubstituted trinorbornanediol yielding only the minor singly charged ions [M–H+Cu]⁺, [2M–H+Cu]⁺ and [2M+CuX]⁺. No clear differences were noted for cobalt complex formation, especially for cis‐2,3‐disubstituted isomers. However, 2,5‐disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo‐isomer. trans‐Isomers gave rise to abundant [3M–H+Co]⁺ ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans‐2,3‐ and trans‐2,5‐diols. To differentiate cis‐2,3‐isomers, the collision‐induced dissociation (CID) products for [3M+Co]²⁺, [M+CoOAc]⁺, [2M–H+Co]⁺ and [2M+CoOAc]⁺ cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc]⁺ and [2M–H+Co]⁺ were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Chiral Supramolecular Switches Based on (R)‐Binaphthalene–Bipyridinium Guests and Cucurbituril Hosts

We designed and synthesized the three molecular tweezers 1 a – c ⁴⁺ containing an electron acceptor 4,4′‐bipyridinium (BPY²⁺) unit in each of the two arms and an (R)‐2,2′‐dioxy‐1,1′‐binaphthyl (BIN) unit that plays the role of chiral centre and the hinge of the structure. Each BPY²⁺ unit is connected to the BIN hinge by an alkyl chain formed by two‐ ( 1 a ⁴⁺), four‐ ( 1 b ⁴⁺), or six‐CH₂ ( 1 c ⁴⁺) groups. The behavior of 1 a – c ⁴⁺ upon chemical or photochemical reduction in the absence and in the presence of cucurbit[8]uril (CB[8]) or cucurbit[7]uril (CB[7]) as macrocyclic hosts for the bipyridinium units has been studied in aqueous solution. A detailed analysis of the UV/Vis absorption and circular dichroism (CD) spectra shows that the helicity of the BIN unit can be reversibly modulated by reduction of the BPY²⁺ units, or by association with cucurbiturils. Upon reduction of 1 a – c ⁴⁺ compounds, the formed BPY^{+ .} units undergo intramolecular dimerization with a concomitant change in the BIN dihedral angle, which depends on the length of the alkyl spacers. The alkyl linkers also play an important role in association to cucurbiturils. Compound 1 a ⁴⁺, because of its short carbon chain, associates to the bulky CB[8] in a 1:1 ratio, whereas in the case of the smaller host compound CB[7] a 1:2 complex is obtained. Compounds 1 b ⁴⁺ and 1 c ⁴⁺, which have longer linkers, associate to two cucurbiturils regardless of their sizes. In all cases, association with CB[8] causes an increase of the BIN dihedral angle, whereas the formation of CB[7] complexes causes an angle decrease. Reduction of the CB[8] complexes results in an enhancement of the BPY^{+ .} dimerization with respect to free 1 a – c ⁴⁺ and causes a noticeable decrease of the BIN dihedral angle, because the BPY^{+ .} units of the two arms have to enter into the same macrocycle. The dimer formation in the CB[8] complexes characterized by a 1:2 ratio implies the release of one macrocycle showing that the binding stoichiometry of these host–guest complexes can be switched from 1:2 to 1:1 by changing the redox state of the guest. When the reduction is performed on the CB[7] complexes, dimer formation is totally inhibited, as expected because the CB[7] cavity cannot host two BPY^{+ .} units.     

Theoretical Study of the Cycloaddition Reaction of a Tungsten‐Containing Carbonyl Ylide

The [3+2] cycloaddition reaction of a tungsten‐containing carbonyl ylide with methyl vinyl ether and the insertion reactions of the nonstabilized carbene complex intermediates produced have been investigated through the use of B3LYP density functional theory. The [3+2] cycloaddition reaction of the tungsten‐containing carbonyl ylide has been proven to proceed concertedly, reversibly, and with high endo selectivity. The intermolecular Si? H insertion reactions of the carbene complex intermediates have been proven to be favored over the intramolecular C? H insertion, in good agreement with experimental results. Moreover, the kinetic endo/exo ratio of the [3+2] cycloaddition reaction has been shown to determine the endo/exo selectivity of the Si? H insertion products. In addition, secondary orbital interactions involving the benzene ring and the carbonyl ligand on the metal center have turned out to strongly influence the high endo selectivity of the [3+2] cycloaddition reaction with methyl vinyl ether.     

Synthesis of Enantiopure Benzo Fused Cyclic Sulfoximines Through Stereoselective [3+2] Cycloaddition between N-tert-Butanesulfinyl [(2-Pyridyl)sulfonyl]-difluoromethyl Ketimines and Arynes

The previously developed stereoselective [3+2] cycloaddition between N-tert-butanesulfinyl ketimines and arynes has been extended to the synthesis of enantiopure [(2-pyridyl)sulfonyl]difluoromethylated cyclic sulfoximines. The use of 2-PySO₂CF₂ as the facilitating group offers new opportunities for the elaboration of the [3+2] cycloaddition products by virtue of the diverse relativity of 2-pyridyl sulfones.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Synthesis of Oligomer and Styrene Polymer-supported Calix[4]arene Derivatives and Selective Extraction of Fe3+

Five new polymeric compounds containing more than one calix[4]arene have been synthesized by reacting an oligomer with 5,11,17,23-tetrakis[(diethylamino)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (L1), 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L2), and p-nitrocalix[4]arene (L3), and chloromethylated polystyrene with 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L4) and p-nitrocalix[4]arene (L5). These compounds were studied by the selective extraction of Fe³⁺ cation from the aqueous phase into the organic phase and was carried out by using compounds L1–L5. It was observed that the polymer support attached to the lower rim of p-nitrocalix[4]arene was the most efficient carrier of Fe³⁺ in the extraction process.     

Theoretical studies of spin state‐specific [2 + 2] and [5 + 2] photocycloaddition reactions of n‐(1‐penten‐5‐yl)maleimide

N‐alkenyl maleimides are found to exhibit spin state‐specific chemoselectivities for [2 + 2] and [5 + 2] photocycloadditions; but, reaction mechanism is still unclear. In this work, we have used high‐level electronic structure methods (DFT, CASSCF, and CASPT2) to explore [2 + 2] and [5 + 2] photocycloaddition reaction paths of an N‐alkenyl maleimide in the S₁ and T₁ states as well as relevant photophysical processes. It is found that in the S₁ state [5 + 2] photocycloaddition reaction is barrierless and thus overwhelmingly dominant; [2 + 2] photocycloaddition reaction is unimportant because of its large barrier. On the contrary, in the T₁ state [2 + 2] photocycloaddition reaction is much more favorable than [5 + 2] photocyclo‐addition reaction. Mechanistically, both S₁ [5 + 2] and T₁ [2 + 2] photocycloaddition reactions occur in a stepwise, nonadiabatic means. In the S₁ [5 + 2] reaction, the secondary C atom of the ethenyl moiety first attacks the N atom of the maleimide moiety forming an S₁ intermediate, which then decays to the S₀ state as a result of an S₁ → S₀ internal conversion. In the T₁ [2 + 2] reaction, the terminal C atom of the ethenyl moiety first attacks the C atom of the maleimide moiety, followed by a T₁ → S₀ intersystem crossing process to the S₀ state. In the S₀ state, the second C C bond is formed. Our present computational results not only rationalize available experiments but also provide new mechanistic insights. © 2017 Wiley Periodicals, Inc.     

Binding behaviors of para-dicyclohexanocucurbit[6]uril and meta-tricyclohexanocucurbit[6]uril with dialkyl viologens

The binding behaviours of para-dicyclohexanocucurbit[6]uril (Cy₂Q[6]) and meta-tricyclohexanocucurbit[6]uril (Cy₃Q[6]) with a series of dialkyl viologens (MV²⁺, EV²⁺, PV²⁺, BV²⁺, FV²⁺ and HV²⁺) have been investigated by various methods. In the aqueous solution, ¹H NMR spectra suggest that the alkyl chains are more favourably encapsulated into the hydrophobic cavities of both hosts than the aromatic rings. Cyclic voltammograms (CV) curves show that the Cy₂Q[6] or Cy₃Q[6] bind the charged viologens more strongly than the reduced viologens. Isothermal titration calorimetry (ITC) data reveal that the binding processes of both hosts with viologens are enthalpic driven. In the solid state, the PV²⁺, BV²⁺ guests and two Cy₃Q[6] hosts generated dumbbell-shaped structures, with two Cy₃Q[6] hosts residing over two terminal alkyl chains of the guests.     

Oxidation reactions in triterpenes under chemical ionization conditions

From a collisional activation spectral study it has been found that certain triterpene alcohols with an ursane or oleanane skeleton undergo oxidation to the corresponding ketones under chemical ionization (NH₃) conditions giving rise to abundant [M + NH₄ ? 2]⁺ ions. Mass-analysed ion kinetic energy and B²/E scan results indicate that both [M + NH₄]⁺ and [M + N₂H₇ ? 2]⁺ ions contribute to the formation of the [M + NH₄ ? 2]⁺ ion.     

A Cucurbit[8]uril 2:2 Complex with a Negative pKa Shift

A viologen derivative carrying a benzimidazole group ( V-P-I ²⁺; viologen–phenylene–imidazole V-P-I ) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK_a, by more than 1 pH unit, contrasting with the positive pK_a shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation. The addition of CB[8] to a solution containing V-P- I ³⁺ indeed released protons as monitored by pH-metry and visualized by a coloured indicator. This property was used to induce a host/guest swapping, accompanied by a proton transfer, between V-P-I ³⁺ ⋅ CB[7] and a CB[8] complex of 1-methyl-4-(4-pyridyl)pyridinium. The origin of this negative pK_a shift is proposed to stand in an ideal charge state, and in the position of the two pH-responsive fragments inside the two CB[8] which, alike residues engulfed in proteins, favour the deprotonated form of the guest molecules. Such proton release triggered by a recognition event is reminiscent of several biological processes and may open new avenues toward bioinspired enzyme mimics catalyzing proton transfer or chemical reactions.     

Isolation and Structural Determination of a Hexacoordinated Antimony(V) Dication

The hexacoordinated antimony(V) dication [(ppy)₃Sb]²⁺ ([ 1 ]²⁺; ppy=2-(2-pyridyl)phenyl), stabilized by three intramolecular donor–acceptor interactions, has been isolated as its hexachloroantimonate salt [ 1 ][SbCl₆]₂, prepared by the oxidative addition of chlorine to the neutral stibine [(ppy)₃Sb] ( 1 ), followed by the abstraction of chloride. Air-stable [ 1 ][SbCl₆]₂ exhibits remarkable thermal stability and the three ppy ligands on the antimony atom are shown to be magnetically inequivalent in the ¹H and ¹³C NMR spectra. A hexacoordinated, meridional octahedral bonding geometry has been determined for [ 1 ][SbCl₆]₂ by X-ray crystallographic analysis. Theoretical calculations were performed to investigate why the meridional form was generated preferentially over the facial form. In addition, the dynamics of the ppy ligands were investigated by variable-temperature ¹H NMR spectroscopy. The potential to generate dications by using a single-electron-transfer reagent has also been investigated. The dication [ 1 ]²⁺ is the first [12–Sb–6]²⁺ chemical species to have been structurally determined.     

Bis‐Lactam Peptide [i,i + 4]‐Stapling

Even though the bis‐lactam peptide stapling with the [i, i + 7] and the [i, i + 11] systems has been known to be able to afford % α‐helicity values up to 100% (25°C), the performance of the bis‐lactam peptide stapling with the [i, i + 4] system in current literature has been mediocre (% α‐helicity ≦40%, 25°C). In the current study, we found that high % α‐helicity is also obtainable with the bis‐lactam [i, i + 4]‐stapling by demonstrating with our model peptide sequence that the bis‐lactam [i, i + 4]‐stapling with N^ε‐para‐phenylenediacetyl‐lysine was able to afford a % α‐helicity value of ~64.1% (25°C). Therefore, the bis‐lactam [i, i + 4]‐stapling could also be an efficacious peptide stapling mode that can be employed for biomedical applications.