Synthese von ‘Push-Pull’-Oligoacetylenen

Synthesis of ‘Push-Pull’-OligoAcetylenes ‘Push-pull’ triacetylenes 11a , b , c , as well as ‘push-pull’ tetraacetylene 13b have been prepared by reaction of the corresponding trichloroene(oligoinyl)amines 9 and 10 with 2 mol-equiv. of BuLi followed by acylation. The sequences (Schemes 3 and 4) are very simple and straightforward, they could in principle be applied to the synthesis of ‘push-pull’ pentaAcetylenes 15 and hexaacetylenes 17 (Scheme 5). Main limitations are the moderate yields as well as the low thermal stability of push-pull oligoacetylenes.     

Synthese, 13C-NMR-Spektren und räumliche Struktur von ‘Push-Pull’-Diacetylenen

Synthesis, ¹³C-NMR Spectra, and X-Ray Investigation of ‘Push-Pull’ Diacetylenes Phenyl-substituted ‘push-pull’ diacetylenes 1f and 1g have been prepared by acetylation and benzoylation of the appropriate lithiodiynylamines 4 (Scheme 2). ¹³C-NMR spectra of diacetylenes 1a–g (Table 1) are discussed with respect to the expected polarisation of the diacetylene unit by ‘push’ and ‘pull’ substituents. X-Ray investigations of 1c , 1e , and 1f have been performed in view of the planned solid-state polymerisation of ‘push-pull’ diacetylenes. In the crystalline state, diacetylenes 1c and 1f are stacked, however, the stacking parameters do not allow a solid-state polymerisation.     

Synthese von ‘Push-Pull’-Diacetylenen

Synthesis of ‘Push-Pull’ Diacetylenes The first synthesis of push-pull diacetylenes of type 1 is described. Reaction of perchlorobutenyne ( 8 ) with two equivalents of dialkylamine, followed by dechlorination using two equivalents of butyllithium gives lithio-dialkylamino-diynes 7 . Final acylation of these intermediates leads to push-pull diacetylenes 1b–1e in good yields. The method allows the introduction of both push and pull substituents in a simple one-pot-procedure. In addition, 1a is prepared by hydroxymethylation of lithio-morpholino-diyne 7c , followed by oxidation with manganese dioxide in acetone.     

3J(H,H) Coupling Constants as a Simple Criterion for π Delocalization of Pentafulvenes and Pentafulvalenes

A simple criterion for estimating the extent of π delocalization in the five-membered ring of pentafulvenes and pentafulvalenes is described. It is based on the fact that changes of bond lengths (induced by exocyclic substituents R¹-R² of 1 ) are reflected by systematic changes of ³J(H,H) values, so that linear correlations of σ vs, ³J(H,H)are obtained. Plots of that type (Fig. 1) are very useful for determining the extent of π delocalization of various pentafulvalenes 2 – 5 (Fig. 3) which show a very similar behavior to pentafulvenes. In principle, these plots could additionally be used for estimating substituent constants σ or for approximating the extent of π overlap between exocyclic substituents and the π system of pentafulvenes. Charge-density effects of pentafulvenes and pentafulvalenes are observed by substituen-induced shifts of the ring C-atoms (Fig. 4).     

Festkörper-Polymerisation eines ‘Push-Pull’-Diacetylens

Solid-State Polymerisation of a ‘Push-Pull’-Diacetylene Solid-state polymerisation of ‘push-pull’-diacetylene 5-(diphenylamino)-1-phenylpenta-2,4-diyn-1-one ( 1d ), initiated by heating of crystals of 1d at 90°, gives ‘push-pull’ poly-diacetylene 2d . X-Ray results and spectroscopic data of monomer 1d as well as of polymer 2d are discussed.     

Improved Purification of C60 and Formation of σ- and π-Homoaromatic methano-bridged fullerenes by reaction with alkyl diazoacetates

A rapid and inexpensive method for the large-scale purification of C₆₀ is the simple filtration of the toluenesoluble extract of commercial fullerene soot through a short plug of charcoal/silica gel with toluene as the eluent. Reactions of C₆₀ with ethyl and tert-butyl diazoacetates in refluxing toluene lead to the formation of the (alkoxycarbonyl)methylene-bridged isomers 1a – 3a and 1b – 3b , respectively, which can be equilibrated, upon further heating, into the single compounds 1a and 1b , respectively. Isomers 1a / b possess the methano bridge at the 6–6 ring junction, whereas structures 2a / b and 3a / b are bridged at the 6–5 junction. A dramatic influence of local and π-ring current anisotropic effects of the fullerene sphere on the NMR chemical shifts of the methine protons in the bridge is observed: the chemical shifts of the protons located over a pentagon ring in 2a / b and over a hexagon ring in 3a / b differ by Δδ = 3.47 and 3.45 ppm, respectively. The analysis of the ¹³C-NMR chemical shifts of the bridgehead C-atoms and the ¹J(C,H) coupling constants for the methano-bridge atoms reveals conclusively that the 6-5-ring-bridged structures 2a / 2b and 3a / 3b are π-homoaromatic (‘open’ transannular bond) and the 6-6-ring-bridged structures 1a / b are π-homoaromatic (‘closed’ transannular bond). The electronic absorption spectra show that π-homoconjugation in 2a / b and 3a / b represents a much smaller electronic perturbation of the original C₆₀ chromophore than σ-homoconjugation in 1a / b . The results of this study demonstrate an impressive linkage between the chemistry of methano-bridged annulenes and methano-bridged fullerenes.     

Synthese von ‘Push-Pull’- Eninen

Synthesis of ‘Push-Pull’ Enynes ‘Push-pull’ enynes 1a–1f are easily available by Pd catalyzed coupling of stannyl-ynamines 15 and silylynamines 16 with β-iodo-enones 8 (Schemes 7 and 8).     

Experimental and Theoretical Conformational Analysis of 5‐Benzylimidazolidin‐4‐one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield‐Wiper’ Effect in Organocatalysis

The PF₆ salts of 5‐benzyl‐1‐isopropylidene‐ and 5‐benzyl‐1‐cinnamylidene‐3‐methylimidazolidin‐4‐ones 1 (Scheme) with various substituents in the 2‐position have been prepared, and single crystals suitable for X‐ray structure determination have been obtained of 14 such compounds, i.e., 2 – 10 and 12 – 16 (Figs. 2–5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle, in contact with the cis‐substituent at C(2) (staggered conformation A ; Figs. 1–3); in three structures, the Ph ring lies above the iminium π‐plane (staggered conformation B ; Figs. 1 and 4); in two structures, the benzylic C? C bond has an eclipsing conformation ( C ; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the N?C‐π‐system, and the cis‐substituent at C(2) of the heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic C? C bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may be a kind of ‘escape’. State‐of‐the‐art quantum‐chemical methods, with large AO basic sets (near the limit) for the single‐point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4 / 12, 5 – 7, 13 , and 16 (Table) in the two staggered conformations, A and B , with the benzylic Ph group above the ring and above the iminium π‐system, respectively. In all cases, the more stable computed conformer (‘isolated‐molecule’ structure) corresponds to the one present in the crystal (overlay in Fig. 7). The energy differences are small (≤2 kcal/mol) which, together with the result of a potential‐curve calculation for the rotation around the benzylic C? C bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in ‘contact’ with the cis‐substituent in conformation A ) for DFT and other quantum‐chemical computations is demonstrated; the benzyl‐imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels–Alder reactions, and many other transformations involving α,β‐unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5‐benzyl‐imidazolidinones as enantioselective catalysts.     

Reaction of γ‐Hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides under the ‘Direct Amide Cyclization’ Conditions

The preparation of the title compounds was achieved via the ‘azirine/oxazolone method’ starting from the corresponding γ‐hydroxy acids. Upon subjecting the γ‐hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides 4 to the so‐called ‘direct amide cyclization’ (DAC) conditions, chlorinated acids 11 or imino lactones 12 were obtained as the sole products instead of the expected cyclodepsipeptides A or their cyclodimers (Scheme 4). Variation of the substituents in 4 did not affect the outcome of the reaction and a mechanism for the formation of both products from the intermediate oxazolone 13 has been proposed. Under the acidic conditions of the DAC, the imino lactones are formed as their HCl salts 12 , which, in polar solvents or on silica gel, reacted further to give the chlorinated acids 11 . Stabilization of the imino lactones was achieved by increasing the substitution in the five‐membered ring, and their structure, in the form of the hydrochlorides, was established independently by X‐ray crystallography (Fig. 4). A derivative 15 of the imino lactone 12a was prepared by the reaction with the 2H‐azirin‐3‐amine 10a ; its structure was also established by an X‐ray crystal‐structure determination (Fig. 3). Furthermore, the structures of the ω‐chloro acids 11a and 11b were determined by X‐ray crystallography (Fig. 2).     

Versuche zur Synthese von ‘Push-Pull’-Diacetylenen

Attempted Synthesis of Push-Pull Diacetylenes Two alternative synthesis of push-pull diacetylenes of type 1 (5-amino-2,4-alkadiynals) are investigated. A bromination-dehydrobromination sequence starting with 5-dimethylamino-2,4-pentadienal ( 2 ) as well as the application of the well-known Cadiot-Chodkiewicz coupling reaction give new intermediates 3–5 , and 7 and 8 , respectively, but fail to give the target molecules 1 .     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Photoinduzierte Cycloadditionen von 2,2-Dimethyl-3-phenyl-2H-azirin an Nitrile und «push-pull»-Olefine. 43. Mitteilung über Photoreaktionen

Photoinduced Cycloadditions of 2,2-Dimethyl-3-phenyl-2H-azirine with Nitriles and ‘push-pull’ Olefines. Electron deficient nitriles of the type 5a–e in contrast to nonactivated nitriles undergo regiospecific [2+3]cycloadditions to benzonitrile isopropylide ( 2b ), which was generated in situ by irradiation of 2,2-dimethyl-3-phenyl-2H-azirine ( 1b ), to yield the 2H-imidazole derivatives 6a – e (Scheme 2). The structure of the photoproducts was mainly deduced from ¹³C-NMR. and mass spectrometry. Whereas normal olefins or enolethers do not react with 2b , push-pull olefins of the type 10a – d readily undergo the cycloaddition to give the 3-alkoxy-5,5-dimethyl-2-phenyl-1-pyrrolines 11a – d (Scheme 3 and 4). The structure of the photoproducts 11a – d indicates that the regiospecificity of the cycloaddition corresponds to that of acrylonitriles and acrylesters with 2b .     

Cyano‐Bridged ‘Oximato’ Complexes: Synthesis,Structure, and Catalase‐Like Activities

The reaction of the ‘oximato’‐ligand precursor A (Fig. 1) and metal salts with KCN gave two mononuclear complexes [ML(CN)(H₂O)_n](ClO₄) ( 1 and 2 ; L={N‐(hydroxy‐κO)‐α‐oxo‐N′‐[(pyridin‐2‐yl‐κN)methyl[1,1′‐biphenyl]‐4‐ethanimidamidato‐κN′}; M=Co^II ( 1 ), Cu^II ( 2 ); n=2 for Co^II, n=0 for Cu^II; Figs. 2 and 3). The new cyano‐bridged pentanuclear ‘oximato’ complexes [{ML(H₂O)_n(NC)}₄M¹(H₂O)_x](ClO₄)₂ ( 3 – 6 ) and trinuclear complexes [{ML(H₂O)_n(NC)}₂M¹L](ClO₄) ( 7 – 10 ) ([M¹=Mn^II, Cu^II; x=2 for Mn^II, x=0 for Cu^II] were synthesized from mononuclear complexes and characterized by elemental analyses, magnetic susceptibility, molar conductance, and IR and thermal analysis. The four [ML(CN)(H₂O)_n]⁺ moieties are connected by a metal(II) ion in the pentanuclear complexe 3 – 6 , each one involving four cyano bridging ligands (Fig. 4). The central metal ion displays a square‐planar or octahedral geometry, with the cyano bridging ligands forming the equatorial plane. The axial positions are occupied by two aqua ligands in the case of the central Mn‐atom. The two [ML(CN)(H₂O)_n]⁺ moieties and an ‘oximato’ ligand are connected by a metal(II) ion in the trinuclear complexes 7 – 10 , each one involving two cyano bridging ligands (Fig. 5). The central metal ions display a distorted square‐pyramidal geometry, with two cyano bridging ligands and the donor atoms of the tridentate ‘oximato’ ligand. Moreover catalytic activities of the complexes for the disproportionation of hydrogen peroxide (H₂O₂) were also investigated in the presence of 1H‐imidazole. The synthesized homopolynuclear Cu^II complexes 6 and 10 displayed eficiency in disproportion reactions of H₂O₂ producing H₂O and dioxygen thus showing catalase‐like activity.     

1H-and 13C-NMR Investigation of Pentafulvenes

¹H- and ¹³C-NMR spectra of a series of 6-(p-X-phenyl)pentafulvenes 1 – 9 as well as of 6-R-substituted and 6,6-R¹,R²-disubstituted pentafulvenes 10 – 23 have been analysed. It turns out that the π-system of pentafulvenes is an attractive probe for the investigation of electronic substituent effects. Changes of vicinal H,H-coupling constants with increasing electron-donating capacity of the substituents X and R are interpreted in terms of an increasing π delocalisation in the 5-membered ring, and linear correlations of Hammett Substituent constants σ or MNDO-calculated C–C bond lengths and ³J values are observed. On the other hand, a systematic high-field shift of ₁₃C chemical shifts of the ring C-atoms is induced by electron-releasing substituents R and X, which decreases in the series C(5) > C(2)/C(3) > C(1)/C(4), and which mainly reflects changes in π-charge density.     

Oligonucleotides Containing 7‐Deaza‐2′‐deoxyinosine as Universal Nucleoside: Synthesis of 7‐Halogenated and 7‐Alkynylated Derivatives,Ambiguous Base Pairing,and Dye Functionalization by the Alkyne–Azide ‘Click’ Reaction

Oligonucleotides containing 7‐deaza‐2′‐deoxyinosine derivatives bearing 7‐halogen substituents or 7‐alkynyl groups were prepared. For this, the phosphoramidites 2b – 2g containing 7‐substituted 7‐deaza‐2′‐deoxyinosine analogues 1b – 1g were synthesized (Scheme 2). Hybridization experiments with modified oligonucleotides demonstrate that all 2′‐deoxyinosine derivatives show ambiguous base pairing, as 2′‐deoxyinosine does. The duplex stability decreases in the order C_d>A_d>T_d>G_d when 2b – 2g pair with these canonical nucleosides (Table 6). The self‐complementary duplexes 5′‐d(F⁷c⁷I‐C)₆, d(Br⁷c⁷I‐C)₆, and d(I⁷c⁷I‐C)₆ are more stable than the parent duplex d(c⁷I‐C)₆ (Table 7). An oligonucleotide containing the octa‐1,7‐diyn‐1‐yl derivative 1g , i.e., 27 , was functionalized with the nonfluorescent 3‐azido‐7‐hydroxycoumarin ( 28 ) by the Huisgen–Sharpless–Meldal cycloaddition ‘click’ reaction to afford the highly fluorescent oligonucleotide conjugate 29 (Scheme 3). Consequently, oligonucleotides incorporating the derivative 1g bearing a terminal C?C bond show a number of favorable properties: i) it is possible to activate them by labeling with reporter molecules employing the ‘click’ chemistry. ii) Space demanding residues introduced in the 7‐position of the 7‐deazapurine base does not interfere with duplex structure and stability (Table 8). iii) The ambiguous pairing character of the nucleobase makes them universal probes for numerous applications in oligonucleotide chemistry, molecular biology, and nanobiotechnology.     

Kupfer(II)-chlorid-katalysierte ‘Carben-Dimerisierung’ von 1-Halogeno-1-Lithiocyclopropanen: Ein einfacher Zugang zu Bi(cyclopropylidenen)

Copper(II)-Chloride Catalyzed ‘Carbene Dimerization’ of 1-Halogeno-1-lithiocyclopropanes: A Simple Access to Bi(cyclopropylidenes) A series of 13 bi(cyclopropylidenes) 11 are prepared in a simple one-pot reaction by halogeno-lithio exchange between 1,1-dibromocyclopropanes 1a – n and BuLi, in most cases at ?95°, to give 1-bromo-1-lithiocyclopropanes 2a – n , followed by treatment with CuCl₂ at low temperature and a simple workup at room temperature (Scheme 3c and Table 1). The yields of bi(cyclopropylidenes) 11 strongly depend on reaction parameters, as explicitly shown for the conversion 1f →→ 11f (Tables 2–8). Mixed couplings between two different carbenoids are possible (Scheme 4), while diastereoselectivity of the active transition-metal complex seems to be low. The structures of bi(cyclopropylidenes) 11 are confirmed by spectroscopic data as well as by X-ray analysis of an isolated crystalline diastereoisomer of 11k (Fig. 1).     

Definitive Proof for the Operation of Isotopically Sensitive Branching (‘Metabolic Switching’) in FeI-Mediated C?H Bond Activation in the Gas Phase Short Communication

Rigorous regio- and stereospecific labeling experiments are performed to demonstrate the operation of the previously suggested operation of ‘isotopically sensitive branching’ in Fe^I-mediated C? H bond activation. For the hexane-1,6-diol/Fe⁺-complex, it is shown that dehydrogenation involves specifically the central C(3)/C(4) position, and the study of the stereospecifically labeled D ,L - and meso-[3,4-D₂]-isotompomers 1e and 1f demonstrates that dehydrogenation proceedes via two competing pathways (i.e. ‘anti’- vs. ‘syn’-route). The contribution of these routes to the product formation is – due to a kinetic isotope effect – controlled by the relative configuration at the labeled positions C(3)/C(4). For the D ,L -form 1e , we estimate a ratio of 49:1 in favor of the ‘anti’-route; due to an isotope effect, this ratio drops to 4.3:1 for the meso-form 1f .     

Oligosaccharide Analogues of Polysaccharides. Part 12. Synthesis of ‘acetyleno-saccharide’-derived cyclodextrin analogues

‘Acetyleno-oligosaccharides’ in which two terminal ethynyl substituents enclose an angle (significantly) below 180° are building blocks for the preparation of cyclodextrin analogues. This is illustrated by the preparation of a cyclotrimer and a cyclotetramer; the C₃-symmetrical cyclotrimer 18 (Scheme 1) was synthesized in 13 steps (7.7%) and the C₄-symmetrical cyclotetramer 51 (Scheme 3) in 14 steps (4.3%) from the known dialkyne 21. The solubilities of 18 and 51 in H₂O were determined by gravimetry; a saturated solution is 130 mM in the trimer 18 and 12.8 mM in the tetramer 51 . The dependence of the optical rotation of 18 and 51 in H₂O on the concentration, and the concentration dependence of the ¹H-NMR chemical shift of the signals of the ¹CH groups of 51 (D₂O) suggest that there is no significant self-association of 18 and 51 .     

The ‘t‐Amino Effect’ of ortho‐Nitroso Amines. Synthesis of 2,6‐Diaminoadenine Derivatives from 6‐(Dialkylamino)‐5‐nitrosopyrimidines

The ‘t‐amino effect’ of amino‐nitroso compounds was documented by preparing the (dialkylamino)‐nitroso pyrimidines 4 – 18 , and cyclising them under thermal conditions in high yields to the purine derivatives 19 – 32 . The reactivity of the amino‐nitroso‐pyrimidines, particularly of 17 derived from diethyl iminodiacetate, and of 19 , derived from 1‐phenylimidazolidine, correlates with the stability of the intermediate azomethine ylide. Thermolysis of the amino‐nitroso‐pyrimidines 34 – 37 , possessing dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to 38 – 41 .     

Synthese neuer Heptafulvene,Röntgenstrukturanalyse von ‘8,8-(1′,4′-Dioxotetramethylen)heptafulven’(2-(Cyclohepta-2,4,6-trien-1-yliden)cyclopentan-1,3-dion)

Synthesis of New Heptafulvenes; X-Ray Analysis of ‘8,8-(1′,4′-Dioxotetramethylene)heptafulvene’ (2-(Cyclohepta-2,4,6-trien-1-ylidene)cyclopentane-1,3-dione) Experimental procedures for the synthesis of heptafulvene ( 3a ), 8,8-tetramethylene heptafulvene ( 3c ) and ‘8,8-(1′,4′-dioxotetramethylene) heptafulvene’ (2-(cyclohepta-2,4,6-trien-1-ylidene)-cyclopentane-1,3-dion; 3d ) are described. The most important sequences include a low-temperature reaction of tropylium salts with lithium or Grignard carbenoids (Scheme 1) to give 3a and 3b as well as hydride abstraction from substituted cycloheptatrienes followed by deprotonation to give 3c and 3d . Limitations of these sequences are discussed. Two other heptafulvenes 3h and 3i are available by silylation of heptafulvenolates according to well-known procedures. NMR-Spectroscopic evidence as well as an X-ray analysis of 3d are presented. Compound 3d is a relatively polar heptafulvene with a planarised seven-membered ring as well as a partly delocalized π system.