Total synthesis of Comfreyn A and structural analogues via two photochemical key steps.

In this work the influence of o-fluorine substituents on the photo-dehydro-Diels-Alder (PDDA) reaction was investigated and the findings of this study were applied to the total synthesis of natural products. The reactant molecules consisted of two alkyl arylpropiolates, connected by a suberic acid tether and bearing fluorine substituents in each of the o-positions. While quantum chemical calculations suggested that a fluorine substituent prevents an attack of the adjacent carbon atom in the second C-C bond forming step of the PDDA reaction, this attack took place nevertheless. The subsequent fluoride elimination, assisted by protic solvents or trialkylsilanes, resulted in an "Umpolung" of the 4-position of the cycloallene intermediate enabling the introduction of nucleophiles at this position. The nucleophilic replacement of the second fluorine substituent could also be triggered photochemically. After removal of the tether, the two arene moieties stand nearly perpendicular to each other and a selective excitation of the naphthalene moiety was possible. This led to an intramolecular photoinduced electron transfer (PET) followed by a nucleophilic replacement of the fluoride according to a SR+N1Ar* mechanism. The formed phenolic hydroxyl group underwent spontaneous lactonization with the adjacent ester group. Based on these results, the first total synthesis of the lignan Comfreyn A and some structural analogues were developed.

The Suzuki-Miyaura Cross-Coupling-Claisen Rearrangement-Cross-Metathesis Approach to Prenylated Isoflavones.

Isoflavones were synthesized via Suzuki-Miyaura coupling of 3-iodochromones and para-methoxybenzene- and para-phenolboronic acid. In our hands, conditions commonly used for similar cross couplings turned out to be unsuccessful or difficult to reproduce, for example, due to the unplanned partial cleavage of MOM-protecting groups. Using Pd(dba)2 as a precatalyst and tricyclohexylphosphine as an activating ligand, reliable cross-coupling conditions were identified. In all cases, notably higher yields of isoflavones were obtained with para-phenolboronic acid than with para-methoxybenzene boronic acid. This observation and the commercial availability of para-phenolboronic acid suggest that for the synthesis of the important 3'-prenyl- or 3',5'-diprenylisoflavone substitution pattern a synthetic route that introduces the prenyl substituents after the Pd-catalyzed cross-coupling step, thereby avoiding laborious and protecting-group-intensive multistep syntheses of C-prenylated arene boronic acids, is advantageous.

Tetrahalidometallate(II) Ionic Liquids with More than One Metal: The Effect of Bromide versus Chloride.

Fifteen N-butylpyridinium salts - five monometallic [C4 Py]2 [MBr4 ] and ten bimetallic [C4 Py]2 [M0.5 a M0.5 b Br4 ] (M=Co, Cu, Mn, Ni, Zn) - were synthesized, and their structures and thermal and electrochemical properties were studied. All the compounds are ionic liquids (ILs) with melting points between 64 and 101 °C. Powder and single-crystal X-ray diffraction show that all ILs are isostructural. The electrochemical stability windows of the ILs are between 2 and 3 V. The conductivities at room temperature are between 10-5 and 10-6  S cm-1 . At elevated temperatures, the conductivities reach up to 10-4  S cm-1 at 70 °C. The structures and properties of the current bromide-based ILs were also compared with those of previous examples using chloride ligands, which illustrated differences and similarities between the two groups of ILs.

Studies toward the Total Synthesis of Arylnaphthalene Lignans via a Photo-Dehydro-Diels-Alder (PDDA) Reaction.

An efficient method for the preparation of arylnaphthalene lignans (ANLs) was developed, which is based on the Photo-Dehydro-Diels-Alder (PDDA) reaction. While intermolecular PDDA reactions turned out to be inefficient, the intramolecular variant using suberic acid as tether linking two aryl propiolic esters smoothly provided naphthalenophanes. The irradiations were performed with a previously developed annular continuous-flow reactor and UVB lamps. In this way, the natural products Alashinol D, Taiwanin C, and an unnamed ANL could be prepared.

Ionic Liquids with More than One Metal: Optical and Electrochemical Properties versus d-Block Metal Combinations.

Thirteen N-butylpyridinium salts, including three monometallic [C4 Py]2 [MCl4 ], nine bimetallic [C4 Py]2 [M1-x a Mx b Cl4 ] and one trimetallic compound [C4 Py]2 [M1-y-z a My b Mz c Cl4 ] (M=Co, Cu, Mn; x=0.25, 0.50 or 0.75 and y=z=0.33), were synthesized and their structure and thermal and electrochemical properties were studied. All compounds are ionic liquids (ILs) with melting points between 69 and 93 °C. X-ray diffraction proves that all ILs are isostructural. The conductivity at room temperature is between 10-4 and 10-8  S cm-1 . Some Cu-based ILs reach conductivities of 10-2  S cm-1 , which is, however, probably due to IL dec. This correlates with the optical bandgap measurements indicating the formation of large bandgap semiconductors. At elevated temperatures approaching the melting points, the conductivities reach up to 1.47×10-1  S cm-1 at 70 °C. The electrochemical stability windows of the ILs are between 2.5 and 3.0 V.

Total Syntheses of Prenylated Isoflavones from Erythrina sacleuxii and Their Antibacterial Activity: 5-Deoxy-3'-prenylbiochanin A and Erysubin F.

The prenylated isoflavones 5-deoxyprenylbiochanin A (7-hydroxy-4'-methoxy-3'-prenylisoflavone) and erysubin F (7,4'-dihydroxy-8,3'-diprenylisoflavone) were synthesized for the first time, starting from mono- or di-O-allylated chalcones, and the structure of 5-deoxy-3'-prenylbiochanin A was corroborated by single-crystal X-ray diffraction analysis. Flavanones are key intermediates in the synthesis. Their reaction with hypervalent iodine reagents affords isoflavones via a 2,3-oxidative rearrangement and the corresponding flavone isomers via 2,3-dehydrogenation. This enabled a synthesis of 7,4'-dihydroxy-8,3'-diprenylflavone, a non-natural regioisomer of erysubin F. Erysubin F (8), 7,4'-dihydroxy-8,3'-diprenylflavone (27), and 5-deoxy-3'-prenylbiochanin A (7) were tested against three bacterial strains and one fungal pathogen. All three compounds are inactive against Salmonella enterica subsp. enterica (NCTC 13349), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028), with MIC values greater than 80.0 µM. The diprenylated natural product erysubin F (8) and its flavone isomer 7,4'-dihydroxy-8,3'-diprenylflavone (27) show in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) at MIC values of 15.4 and 20.5 µM, respectively. In contrast, the monoprenylated 5-deoxy-3'-prenylbiochanin A (7) is inactive against this MRSA strain.

The 1,6,7,12-Tetraazaperylene Bridging Ligand as an Electron Reservoir and Its Disulfonato Derivative as Redox Mediator in an Enzyme-Electrode Process.

The homodinuclear ruthenium(II) complex [{Ru(l-N4 Me2 )}2 (µ-tape)](PF6 )4 {[1](PF6 )4 } (l-N4 Me2 =N,N'-dimethyl-2,11-diaza[3.3](2,6)-pyridinophane, tape=1,6,7,12-tetraazaperylene) can store one or two electrons in the energetically low-lying π* orbital of the bridging ligand tape. The corresponding singly and doubly reduced complexes [{Ru(l-N4 Me2 )}2 (µ-tape.- )](PF6 )3 {[2](PF6 )3 } and [{Ru(l-N4 Me2 )}2 (µ-tape2- )](PF6 )2 {[3](PF6 )2 }, respectively, were electrochemically generated, successfully isolated and fully characterized by single-crystal X-ray crystallography, spectroscopic methods and magnetic susceptibility measurements. The singly reduced complex [2](PF6 )3 contains the π-radical tape.- and the doubly reduced [3](PF6 )2 the diamagnetic dianion tape2- as bridging ligand, respectively. Nucleophilic aromatic substitution at the bridging tape in [1]4+ by two sulfite units gave the complex [{Ru(l-N4 Me2 )}2 {µ-tape-(SO3 )2 }]2+ ([4]2+ ). Complex dication [4]2+ was exploited as a redox mediator between an anaerobic homogenous reaction solution of an enzyme system (sulfite/sulfite oxidase) and the electrode via participation of the low-energy π*-orbital of the disulfonato-substituted bridging ligand tape-(SO3 )22- (Ered1 =-0.1 V versus Ag/AgCl/1 m KCl in water).

Study of the Discrepancies between Crystallographic Porosity and Guest Access into Cadmium-Imidazolate Frameworks and Tunable Luminescence Properties by Incorporation of Lanthanides.

An extended member of the isoreticular family of metal-imidazolate framework structures, IFP-6 (IFP=imidazolate framework Potsdam), based on cadmium metal and an in situ functionalized 2-methylimidazolate-4-amide-5-imidate linker is reported. A porous 3D framework with 1D hexagonal channels with accessible pore windows of 0.52 nm has been synthesized by using an ionic liquid (IL) linker precursor. IFP-6 shows significant gas uptake capacity only for CO2 and CH4 at elevated pressure, whereas it does not adsorb N2 , H2 , and CH4 under atmospheric conditions. IFP-6 is assumed to deteriorate at the outside of the material during the activation process. This closing of the metal-organic framework (MOF) pores is proven by positron annihilation lifetime spectroscopy (PALS), which revealed inherent crystal defects. PALS results support the conservation of the inner pores of IFP-6. IFP-6 has also been successfully loaded with luminescent trivalent lanthanide ions (Ln(III) =Tb, Eu, and Sm) in a bottom-up one-pot reaction through the in situ generation of the linker ligand and in situ incorporation of photoluminescent Ln ions into the constituting network. The results of photoluminescence investigations and powder XRD provide evidence that the Ln ions are not doped as connectivity centers into the frameworks, but are instead located within the pores of the MOFs. Under UV light irradiation, Tb@IFP-6 and Eu@IFP-6 (λexc =365 nm) exhibit observable emission changes to a greenish and reddish color, respectively, as a result of strong Ln 4 f emissions.

Photochemical Synthesis of Both Strained and Macrocyclic (1,7)Naphthalenophanes.

Naphthalenophanes are a special type of cyclophanes. While in the past (1,5)-, (1,6)-, and (1,8)naphthalenophanes were successfully prepared by using the photo-dehydro-Diels-Alder (DDA) reaction, access to (1,7)naphthalenophanes by this method was hitherto unknown. After numerous unsuccessful attempts to prepare these compounds by thermal DDA, we found that the photoinitiated variant (PDDA) represents a very efficient method to [k](1,7)naphthalenophanes 13. The scope ranged from highly strained (k = 11, 12) to macrocyclic products (k = 22, 24). The extraordinary reactivity could be explained by folded ground-state geometries of diketones 12 used as reactants of the PDDA. Furthermore, we calculated the ring-strain energies with the help of an isodesmic reaction and evaluated structural and spectroscopic (NMR) consequences of ring strain.

Tetrabromidocuprates(II)-Synthesis, Structure and EPR.

Metal-containing ionic liquids (ILs) are of interest for a variety of technical applications, e.g., particle synthesis and materials with magnetic or thermochromic properties. In this paper we report the synthesis of, and two structures for, some new tetrabromidocuprates(II) with several "onium" cations in comparison to the results of electron paramagnetic resonance (EPR) spectroscopic analyses. The sterically demanding cations were used to separate the paramagnetic Cu(II) ions for EPR measurements. The EPR hyperfine structure in the spectra of these new compounds is not resolved, due to the line broadening resulting from magnetic exchange between the still-incomplete separated paramagnetic Cu(II) centres. For the majority of compounds, the principal g values (g‖ and g⊥) of the tensors could be determined and information on the structural changes in the [CuBr4](2-) anions can be obtained. The complexes have high potential, e.g., as ionic liquids, as precursors for the synthesis of copper bromide particles, as catalytically active or paramagnetic ionic liquids.

Ionogels Based on Poly(methyl methacrylate) and Metal-Containing Ionic Liquids: Correlation between Structure and Mechanical and Electrical Properties.

Ionogels (IGs) based on poly(methyl methacrylate) (PMMA) and the metal-containing ionic liquids (ILs) bis-1-butyl-3-methlimidazolium tetrachloridocuprate(II), tetrachloride cobaltate(II), and tetrachlorido manganate(II) have been synthesized and their mechanical and electrical properties have been correlated with their microstructure. Unlike many previous examples, the current IGs show a decreasing stability in stress-strain experiments on increasing IL fractions. The conductivities of the current IGs are lower than those observed in similar examples in the literature. Both effects are caused by a two-phase structure with micrometer-sized IL-rich domains homogeneously dispersed an IL-deficient continuous PMMA phase. This study demonstrates that the IL-polymer miscibility and the morphology of the IGs are key parameters to control the (macroscopic) properties of IGs.

Dual Role of Acetanilides: Traceless Removal of a Directing Group through Deacetylation/Diazotation and Palladium-Catalyzed C-C-Coupling Reactions.

The acetamide group enables regioselective oxidative ortho-C-H activation reactions, such as Pd-catalyzed acylation. The synthetic utility of these transformations can be significantly enhanced by using the acetamide as a quasi-leaving group in a subsequent conventional Pd-catalyzed coupling or cross-coupling reaction. The concept is illustrated herein for the synthesis of o-alkenyl- and o-arylphenones, which have potential for the synthesis of arylated aromatic heterocycles.

Giant Zn14 molecular building block in hydrogen-bonded network with permanent porosity for gas uptake.

In situ imidazolate-4,5-diamide-2-olate linker generation leads to the formation of a [Zn14(L2)12(O)(OH)2(H2O)4] molecular building block (MBB) with a Zn6 octahedron inscribed in a Zn8 cube. The MBBs connect by amide-amide hydrogen bonds to a 3D robust supramolecular network which can be activated for N2, CO2, CH4, and H2 gas sorption.

Imidazolium 2-substituted 4,5-dicyanoimidazolate ionic liquids: synthesis, crystal structures and structure-thermal property relationships.

Thirty six novel ionic liquids (ILs) with 1-butyl-3-methylimidazolium and 3-methyl-1-octylimidazolium cations paired with 2-substitited 4,5-dicyanoimidazolate anions (substituent at C2 = chloro, bromo, methoxy, vinyl, amino, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and phenyl) have been synthesized and characterized by using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and single-crystal X-ray crystallography. The effects of cation and anion type and structure on the thermal properties of the resulting ionic liquids, including several room temperature ionic liquids (RTILs) are examined and discussed. ILs exhibited large liquid and crystallization ranges and formed glasses on cooling with glass transition temperatures in the range of -22 to -68 °C. The effects of alkyl substituents of the imidazolate anion reflected the crystallization, melting points and thermal decomposition of the ILs. The Coulombic packing force, van der Waals forces and size of the anions can be considered for altering the thermal transitions. Three crystal structures of the ILs were determined and the effects of changes to the cations and anions on the packing of the structure were investigated.

Crystal structure of (2,11-di-aza-[3.3](2,6)pyridino-phane-κ (4) N,N',N'',N''')(1,6,7,12-tetra-aza-perylene-κ (2) N (1),N (12))ruthenium(II) bis-(hexa-fluorido-phosphate) aceto-nitrile 1.422-solvate.

In the title compound, [Ru(C14H16N4)(C16H8N4)](PF6)2·1.422CH3CN, discrete dimers of complex cations, [Ru(L-N4H2)tape](2+) are formed {L-N4H2 = 2,11-di-aza-[3.3](2,6)pyridino-phane; tape = 1,6,7,12-tetra-aza-perylene}, held together by π-π stacking inter-actions via the tape ligand moieties with a centroid-centroid distance of 3.49 (2) Å, assisted by hydrogen bonds between the non-coordinating tape ligand α,α'-di-imine unit and the amine proton of a 2,11-di-aza-[3.3](2,6)-pyridino-phane ligand of the opposite complex cation. The combination of these inter-actions leads to an unusual nearly face-to-face π-π stacking mode. Additional weak C-H⋯N, C-H⋯F, N-H⋯F and P-F⋯π-ring (tape, py) (with F⋯centroid distances of 2.925-3.984 Å) inter-actions are found, leading to a three-dimensional architecture. The Ru(II) atom is coordinated in a distorted octa-hedral geometry, particularly manifested by the Namine-Ru-Namine angle of 153.79 (10)°. The counter-charge is provided by two hexa-fluorido-phosphate anions and the asymmetric unit is completed by aceto-nitrile solvent mol-ecules of crystallization. Disorder was observed for both the hexa-fluorido-phosphate anions as well as the aceto-nitrile solvate mol-ecules, with occupancies for the major moieties of 0.801 (6) for one of the PF6 anions, and a shared occupancy of 0.9215 (17) for the second PF6 anion and a partially occupied aceto-nitrile mol-ecule. A second CH3CN mol-ecule is fully occupied, but 1:1 disordered across a crystallographic inversion center.

(1,6,7,12-Tetra-aza-perylene-κ(2) N,N')bis-(4,4',5,5'-tetra-methyl-2,2'-bipyridyl-κ(2) N,N')ruthenium(II) bis-(hexa-fluorido-phosphate) aceto-nitrile tris-olvate.

In the title compound, rac-[Ru(C14H16N2)2(C16H8N4)](PF6)2·3C2H3N, discrete dimers of complex cations, [Ru(tmbpy)2-tape](2+), of opposite chirality are formed (tmbpy = tetra-methyl-bipyridine; tape = tetraazaperylene), held together by π-π stacking inter-actions between the tetra-aza-perylene moieties with centroid-centroid distances in the range 3.563 (3)-3.837 (3) Å. These inter-actions exhibit a parallel displaced π-π stacking mode. Additional weak C-H⋯π-ring and C-H⋯N and C-H⋯F inter-actions are found, leading to a three-dimensional architecture. The Ru(II) atom is coordinated in a distorted octa-hedral geometry. The counter-charge is provided by two hexa-fluorido-phosphate anions and the asymmetric unit is completed by three aceto-nitrile solvent mol-ecules of crystallization. Four F atoms of one PF6 (-) anion are disordered over three sets of sites with occupancies of 0.517 (3):0.244 (3):0.239 (3). Two aceto-nitrile solvent mol-ecules are highly disordered and their estimated scattering contribution was subtracted from the observed diffraction data using the SQUEEZE option in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155].

µ-1,6,7,12-Tetra-aza-perylene-κ(4) N (1),N (12):N (6),N (7)-bis-[chlorido-(η(6)-p-cymene)ruthenium(II)] bis-(hexa-fluorido-phosphate) acetone disolvate.

In the title compound, [Ru2(C10H14)2Cl2(C16H8N4)](PF6)2·2C3H6O, the binuclear Ru(II) complex dication, [{RuCl(η(6)-cym)}2(µ-tape)](2+), built up by a planar 1,6,7,12-tetra-aza-perylene (tape) bridge, two η(6)-bound cymene (cym) ligands and two chloride ligands, includes an inversion center. The Ru(II) atom shows the typical piano-stool motif for arene coordination. The counter-charge is provided by a hexa-fluorido-phosphate anion and the asymmetric unit is completed by an acetone mol-ecule of crystallization. The components of the structure are connected into a three-dimensional architecture by C-H⋯O/F/Cl inter-actions.

Bromination of eudesmin isolated from araucaria araucana induces epimerization and give bromine derivatives with loss of anti-Candida activity.

Furofuran lignanes show important biological activities for the treatment of infectious diseases, inflammatory and metabolic pathologies. They have been isolated from leaves and barks of many plants. In Chile the native conifer Araucaria araucana produces eudesmin, matairesinol, secoisolariciresinol and lariciresinol in stemwood, branchwood and knotwood. These compounds were previously isolated by laborious flash chromatography on silica gel. Here we report the easy isolation of eudesmin by soxhlet extraction from milled knots of Araucaria araucana with hexane, followed by cryo-crystallization at -20 °C. Upon bromination of the isolated eudesmin epimerization at one benzylic position occurs, giving epieudesmin and the corresponding mono and di-brominated derivatives. The structures were determined by 1D, 2D NMR and X-ray diffraction. The analysis of products against Candida yeast showed that eudesmin has a moderate activity against different strains of Candida from 62.5 to 500 µg/mL. This activity decreases for epieudesmin, while bromine derivatives are not active.

N-2-pyridinylmethyl-N'-arylmethyl-diaminomaleonitriles: new highly selective chromogenic chemodosimeters for copper(II).

Copper chemodosimeters: The copper(II)-promoted air oxidation of 1-3 to form 4-6 permits the highly selective colorimetric detection of Cu(2+) ions. The formation of copper(II) complexes of 4-6 proceeds rapidly, and the chemodosimeters 1-3 are viable at physiological pH.

An isoreticular family of microporous metal-organic frameworks based on zinc and 2-substituted imidazolate-4-amide-5-imidate: syntheses, structures and properties.

We report on a new series of isoreticular frameworks based on zinc and 2-substituted imidazolate-4-amide-5-imidate (IFP-1-4, IFP = imidazolate framework Potsdam) that form one-dimensional, microporous hexagonal channels. Varying R in the 2-substitued linker (R = Me (IFP-1), Cl (IFP-2), Br (IFP-3), Et (IFP-4)) allowed the channel diameter (4.0-1.7 Å), the polarisability and functionality of the channel walls to be tuned. Frameworks IFP-2, IFP-3 and IFP-4 are isostructural to previously reported IFP-1. The structures of IFP-2 and IFP-3 were solved by X-ray crystallographic analyses. The structure of IFP-4 was determined by a combination of PXRD and structure modelling and was confirmed by IR spectroscopy and (1)H MAS and (13)C CP-MAS NMR spectroscopy. All IFPs showed high thermal stability (345-400 °C); IFP-1 and IFP-4 were stable in boiling water for 7 d. A detailed porosity analysis was performed on the basis of adsorption measurements by using various gases. The potential of the materials to undergo specific interactions with CO(2) was investigated by measuring the isosteric heats of adsorption. The capacity to adsorb CH(4) (at 298 K), CO(2) (at 298 K) and H(2) (at 77 K) at high pressure were also investigated. In situ IR spectroscopy showed that CO(2) is physisorbed on IFP-1-4 under dry conditions and that both CO(2) and H(2)O are physisorbed on IFP-1 under moist conditions.