Phenoxaphosphonium Mixed Ylides in Ring Expansion Reaction.

Treatment of mixed phosphonium-iodonium ylides featuring a six-membered phenoxaphosphonium fragment with aqueous tetrafluoroboronic acid induces a rearrangement, resulting in expansion of the phosphacycle and oxidation of the phosphorus atom. The target difficult-to-access dibenzo[b,f][1,4]oxaphosphepine oxides (3 examples) were isolated in excellent yields (up to 95%) as mixtures of stereoisomers. Hydrolysis of a five-membered mixed ylide, a dibenzophosphole derivative, predominantly preserves the phosphole system with cycle expansion occurring as a side process.

Solvation-Anionic Exchange Mechanism of Solvent Extraction: Enhanced U(VI) Uptake by Tetradentate Phenanthroline Ligands.

Phenanthroline diamides (L) demonstrated a unique ability to extract uranium from nitric acid solutions into a polar organic solvent forming complexes of 1:2 stoichiometry as tight ion pairs {[UO2LNO3]+[UO2(NO3)3]-} by a novel extraction mechanism, which is a combination of two already well-known mechanisms: solvation and ion-pair anion exchange. A UV-vis study was used to confirm the formation of such complexes directly in the organic phase. Moreover, chemical synthesis and single crystal growth were performed to confirm unambiguously the structure of the complexes in the solid state.

4-Oxo-7-fluoro-1,10-phenanthroline-2,9-diamides: Synthesis, Structural Features, Lanthanide Complexes, and Am(III)/Ln(III) Solvent Extraction.

A highly efficient synthetic approach was developed for the synthesis of unsymmetrical 1,10-phenanthroline-2,9-diamides with two different substituents in the fourth and seventh positions of the phenanthroline core. The structures of these ligands were confirmed using various spectral methods including 2D-NMR and X-ray analysis. Quantum chemical calculations supported the presence of tautomeric forms of these ligands. Furthermore, it was discovered that these compounds exhibit polydentate ligand behavior toward lanthanide nitrates. The structural characteristics of the complexes formed between these ligands and lanthanide nitrates were investigated both in the solid state and in solution. To further understand the binding properties of these novel unsymmetrical ligands, the binding constants for potential complexes were quantitatively measured by using UV-vis spectrophotometric titration. This allowed for a comprehensive analysis of the binding affinity and stability of these complexes. Extraction experiments of f-elements were performed for symmetrical and unsymmetrical diamides. Overall, this study presents significant advancement in the synthesis and characterization of unsymmetrical 1,10-phenanthroline-2,9-diamides and provides valuable insights into their potential applications as polydentate ligands for lanthanide nitrates.

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations.

Nitrile imine cycloaddition to hydantoins containing an exocyclic C=C double bond has been previously described in a very limited number of examples. In this work, regioselective synthesis of spiro-pyrazoline-imidazolidine-2,4-diones based on a 1,3-dipolar cycloaddition reaction of nitrile imines to 5-methylidene-3-phenyl-hydantoin have been proposed. It was found that, regardless of the nature of the aryl substituents at the terminal C and N atoms of the C-N-N fragment of nitrile imine (electron donor or electron acceptor), cycloaddition to the 5-methylidenhydantoin exocyclic C=C bond proceeds regioselectively, and the terminal nitrogen atom of the nitrile imine connects to the more sterically hindered carbon atom of the double bond, which leads to the formation of a 5-disubstituted pyrazoline ring. The observed cycloaddition regioselectivity was rationalized using DFT calculations of frontier molecular orbital interactions, global CDFT reactivity indices, and minimum energy paths.

[4+2]-Cycloaddition to 5-Methylidene-Hydantoins and 5-Methylidene-2-Thiohydantoins in the Synthesis of Spiro-2-Chalcogenimidazolones.

Novel hydantion and thiohydantoin-based spiro-compounds were prepared via theDiels-Alder reactions between 5-methylidene-hydantoins or 5-methylidene-2-thiohydantoins and 1,3-dienes (cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, isoprene). It was shown that the cycloaddition reactions proceed regioselectively and stereoselectively with the formation of exo-isomers in the reactions with cyclic dienes andthe less sterically hindered products in the reactions with isoprene. Reactions of methylideneimidazolones with cyclopentadiene proceed viaco-heating the reactants; reactions with cyclohexadiene, 2,3-dimethylbutadiene, and isoprene require catalysis by Lewis acids. It was demonstrated that ZnI2 is an effective catalyst in the Diels-Alder reactions of methylidenethiohydantoins with non-activated dienes. The possibility of alkylation and acylation of the obtained spiro-hydantoinsat the N(1)nitrogen atoms with PhCH2Cl or Boc2O and the alkylation of the spiro-thiohydantoinsat the S atoms with MeI or PhCH2Cl in high yields have been demonstrated. The preparativetransformation of spiro-thiohydantoins into corresponding spiro-hydantoinsin mild conditions by treating with 35% aqueous H2O2 or nitrile oxide has been carried out. The obtained compounds show moderate cytotoxicity in the MTT test on MCF7, A549, HEK293T, and VA13 cell lines. Some of the tested compounds demonstrated some antibacterial effect against Escherichia coli (E. coli) BW25113 DTC-pDualrep2 but were almost inactive against E. coli BW25113 LPTD-pDualrep2.

First 24-Membered Macrocyclic 1,10-Phenanthroline-2,9-Diamides-An Efficient Switch from Acidic to Alkaline Extraction of f-Elements.

A reaction of acyl chlorides derived from 1,10-phenanthroline-2,9-dicarboxylic acids with piperazine allows the preparation of the corresponding 24-membered macrocycles in good yield. The structural and spectral properties of these new macrocyclic ligands were thoroughly investigated, revealing promising coordination properties towards f-elements (Am, Eu). It was shown that the prepared ligands can be used for selective extraction of Am(III) from alkaline-carbonate media in presence of Eu(III) with an SFAm/Eu up to 40. Their extraction efficiency is higher than calixarene-type extraction of the Am(III) and Eu(III) pair. Composition of macrocycle-metal complex with Eu(III) was investigated by luminescence and UV-vis spectroscopy. The possibility of such ligands to form complexes of L:Eu = 1:2 stoichiometry is revealed.

[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives-An Approach to Novel Spiroimidazolidinediones.

Approximately 1,3-Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with promising anticancer activity. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were first investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop¼ or using the recently proposed diffusion mixing technique, which led to ~5-15% increases in target compound yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance with the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in the nitrile imine structure and was significantly decreased in reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

Dispirooxindole-ß-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation.

In this work, we present the first synthesis of dispirooxindole-ß-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with ß-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD.

First Example of Fluorinated Phenanthroline Diamides: Synthesis, Structural Study, and Complexation with Lanthanoids.

An efficient approach to the synthesis of diamides of 4,7-difluoro-1,10-phenanthroline-2,9-dicarboxylic acid was elaborated. Direct nucleophilic substitution with 4,7-dichloro-1,10-phenanthroline precursors opened access to difluoro derivatives in high yield. As a result, four new fluorinated ligands were prepared in up to 88% yield. Their structure was proved by a combination of spectral methods and X-ray data. A set of lanthanoid complexes was prepared to demonstrate the utility of new ligands. The structure of the complexes was studied in solid state (IR-spectroscopy, X-ray diffraction) and in solution (NMR-spectroscopy).

First Trifluoromethylated Phenanthrolinediamides: Synthesis, Structure, Stereodynamics and Complexation with Ln(III).

The first examples of 1,10-phenanthroline-2,9-diamides bearing CF3-groups on the side amide substituents were synthesized. Due to stereoisomerism and amide rotation, such complexes have complicated behavior in solutions. Using advanced NMR techniques and X-ray analysis, their structures were completely elucidated. The possibility of the formation of complex compounds with lanthanoids nitrates was shown, and the constants of their stability are quantified. The results obtained are explained in terms of quantum-chemical calculations.

Cu(I)- and Pd(0)-Catalyzed Arylation of Oxadiamines with Fluorinated Halogenobenzenes: Comparison of Efficiency.

The comparison of the possibilities of Pd- and Cu-catalyzed amination reactions using fluorine-containing aryl bromides and iodides with oxadiamines to produce their N,N'-diaryl derivatives was carried out. The dependence of the reactivity of the aryl halides on the nature of the substituents and halogen atoms as well as on the structure of oxadiamines was investigated. It was found that the copper-catalyzed reactions were somewhat comparable with the palladium-mediated processes in the majority of cases, especially in the reactions with para-fluorine- and para-(trifluoromethyl)-substituted aryl halides, although the necessity to use aryl iodides in the Cu(I)-catalyzed amination was obvious. Pd catalysis was found inevitable for the successful amination of more sterically hindered ortho-(trifluoromethyl)aryl bromides.

Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen.

A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker with terminal amide and azide groups for subsequent addition of two different therapeutic and diagnostic agents. The optimal method for this molecular platform synthesis includes (a) solid-phase assembly of the polypeptide linker, (b) coupling of this linker with the vector fragment, (c) attachment of 3-aminopropylazide, and (d) amide and carboxylic groups deprotection. A bimodal theranostic conjugate of the proposed platform with a cytostatic drug (docetaxel) and a fluorescent label (Sulfo-Cy5) was synthesized to demonstrate its possible sequential conjugation with different functional molecules.

6-Polyamino-substituted quinolines: synthesis and multiple metal (CuII, HgII and ZnII) monitoring in aqueous media.

Chemoselective palladium-catalyzed arylation of polyamines with 6-bromoquinoline has been explored to prepare chelators for the detection of metal cations in aqueous media. The introduction of a single aromatic moiety into non-protected polyamine molecules was achieved using the commercially available Pd(dba)2/BINAP precatalyst to afford nitrogen chelators, in which the aromatic signalling unit is directly attached to the polyamine residue. Water-soluble receptors were then synthesized using N-alkylation of these polyamines by hydrophilic coordinating residues. By combining rich photophysical properties of the 6-aminoquinoline unit with a high coordination affinity of chelating polyamines and a hydrophilic character of carboxamido-substituted phosphonic acid diesters in a single molecular device, we synthesized chemosensor 5 for selective double-channel (UV-vis and fluorescence spectroscopies) detection of CuII ions in aqueous media at physiological levels. This receptor is suitable for the analysis of drinking water and fabrication of paper test strips for the naked-eye detection of CuII ions under UV-light. By increasing the number of donor sites we also obtained chemosensor 6 which is efficient for the detection of HgII ions. Moreover, chemosensor 6 is also suitable for multiple detection of metal ions because it chelates not only HgII but also CuII and ZnII ions displaying different responses of emission in the presence of these three cations.

Beyond the Dimer and Trimer: Tetraspiro[2.1.2(5).1.2(9).1.2(13).1(3)] hexadecane-1,3,5,7-tetraone--the Cyclic Tetramer of Carbonylcyclopropane.

Tetraspiro[2.1.2(5).1.2(9).1.2(13).1(3)]hexadecane-1,3,5,7-tetraone 4, a unique tetraketone containing a cyclooctane core and four spiroannelated cyclopropane moieties, represents the previously unknown cyclotetramer of carbonylcyclopropane. For this purpose oxidation of the parent polyspirocyclic hydrocarbon was examined under various oxidative conditions, and the reactivity of oxidants towards methylene groups of the eight-membered cycle, activated by adjacent spirocyclopropane rings, was evaluated and contrasted. Whereas the treatment of tetraspirohexadecane with ozone resulted in monooxidation, its reaction with methyl(trifluoromethyl)dioxirane afforded the product of four-fold oxidation, triketoalcohol 10. Subsequent oxidation of the latter with Dess-Martin periodinane gave the target tetraketone 4.

Base mediated 1,3-dipolar cycloaddition of α-substituted vinyl phosphonates with diazo compounds for synthesis of 3-pyrazolylphosphonates and 5-pyrazolcarboxylates.

5-Aryl-substituted pyrazol-3-ylphosphonates have been conveniently synthesized by 1,3-dipolar cycloaddition of 1-formamidovinylphosphonates and aryldiazomethanes under K2CO3/MeOH conditions at room temperature. These pyrazoles are formed in one pot via spontaneous elimination of formamide. Basic conditions prevent competitive formation of cyclopropylphosphonates. 3-Aryl substituted pyrazol-5-carboxylates can be synthesized by the same methodology from 1-arylvinylphosphonates and ethyl diazoacetate, although a stronger base NaH is necessary to ensure the success of the aromatization stage with the elimination of the diethoxylphosphoryl moiety.

symm-Tetramethylenecyclooctane: en route to polyspirocycles.

A straightforward gram-scale synthesis of 1,3,5,7-tetrakis(methylidene)cyclooctane (TMCO) from commercial adamantane-1,3-dicarboxylic acid has been developed. TMCO exhibits high reactivity toward a number of carbenes and epoxidizing reagents, undergoing multiple cyclopropanations, dihalocyclopropanations, or epoxidations of four double bonds to yield polyspirocyclic products. Stereochemical features of polyspirocyclopropanated compounds have been thoroughly examined in experimental (NMR) and theoretical (DFT) studies. Comprehensive stereochemical assignment of TMCO adducts with dihalocarbenes and spiroepoxy products was achieved. The conditions of the formation of 1-methyl-3,7-bis(methylidene)bicyclo[3.3.1]nonane from the adamantane derivative were optimized, and diadducts of this diene with dihalocarbenes were isolated and characterized.

Ruthenium(II) complexes with phosphonate-substituted phenanthroline ligands as reusable photoredox catalysts.

Ru(II) complexes with polypyridyl ligands (2,2'-bipyridine = bpy, 1,10-phenanthroline = phen) play a central role in the development of photocatalytic organic reactions. In this work, we synthesized four mixed-ligand [Ru(phen)(bpy)2]2+-type complexes (Ru-Pcat-A) bearing two phosphonate substituents P(O)(OH)(OR) (R = H, Et) attached to the phen core at positions 3,8 (Ru-3,8PH and Ru-3,8PHEt) and 4,7 (Ru-4,7PH and Ru-4,7PHEt) of the heterocycle in high yields (87-99%) and characterized them using spectral methods. Single crystal X-ray diffraction was employed to determine the coordination mode of the ditopic phen ligand in Ru-4,7PH. This complex exists as the neutral species and forms a 1D hydrogen-bonded framework in the crystals. The light absorption characteristics were found to be similar for all complexes prepared in this work. However, the emission maxima in aqueous solutions were significantly affected by the substitution of the heterocycle, ranging from 629 nm for Ru-4,7PH to 661 nm for Ru-3,8PHEt. The emission quantum yields in Ar-saturated deionized water showed a strong dependence on the substitution pattern of the phen ligand, with maximal values reaching approximately 0.11 for Ru-4,7PHEt and Ru-4,7PH, which is twice as high as that of the classical [Ru(bpy)3]2+ complex (Ru-bpy). The photocatalytic performance of Ru-Pcat-A was investigated using visible light photoredox catalytic transformations of tertiary amines. With Ru-Pcat-A, we achieved the phosphonylation of N-aryl-1,2,3,4-tetrahydroisoquinolines (THIQs) and cyanation of THIQs and N,N-dimethylaniline in methanol, while a mixture of nitromethane/methanol (1 : 1 v/v) proved to be the optimal solvent for conducting the nitromethylation of THIQs. In the majority of the studied reactions, Ru-4,7PHEt exhibited greater efficiency compared to Ru-bpy, and it could be easily separated from the products using water extraction and reused in the next catalytic cycle. We successfully performed seven consecutive nitromethylation and phosphonylation of N-phenyl-1,2,3,4-tetrahydroisoquinoline using the recycled homogeneous photoredox catalyst.

First 4,7-oxygenated 1,10-phenanthroline-2,9-diamides: synthesis, tautomerism and complexation with REE nitrates.

A new family of phenanthroline ligands was prepared. Hydrolysis of 4,7-dihalogenated 1,10-phenanthroline-2,9-diamides in acidic media leads to the formation of the corresponding 4,7-oxygenated derivatives. These ligands can exist in different tautomeric forms. The tautomerism of 4,7-oxygenated phenanthroline diamides has been investigated using quantum chemical calculations. The unsymmetrical oxo-hydroxy tautomeric form was proved to be the most energetically advantageous according to the spectral data and X-ray analysis. It was shown that 4,7-difluoro derivatives undergo acid hydrolysis more easily when compared to 4,7-dichloro derivatives. The coordination chemistry of 4,7-oxygenated 1,10-phenanthroline-2,9-diamides toward some lanthanide nitrates was investigated. The structures of Ln-complexes thus formed were studied both in the solid state and in solution (XRD analysis and IR, NMR and UV spectroscopy). It was revealed that 4,7-oxygenated ligands adopt the dihydroxy tautomeric form upon coordination with lanthanide nitrates.

[3+2]-Cycloaddition of azomethine ylides to 5-methylidene-3-aryl-2-сhalcogen-imidazolones: access to dispiro indolinone-pyrrolidine-imidazolones.

A synthesis of dispiro derivatives from 5-methylidene-2-chalcogenimidazolones and azomethine ylides generated from isatins and N-substituted α-amino acids has been developed.

Ruthenium(II) complexes with phosphonate-substituted phenanthroline ligands: synthesis, characterization and use in organic photocatalysis.

Ru(II) complexes with polypyridyl ligands play a central role in the development of photocatalytic organic reactions. This work is aimed at the structural modification of such complexes to increase their photocatalytic efficiency and adapt them for the preparation of reusable photocatalytic systems. Nine [Ru(phen)(bpy)2]2+-type complexes (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline) (Ru-Pcat) bearing the P(O)(OEt)2 substituent attached to the phen core directly or through a 1,4-phenylene linker were synthesized and characterized by spectroscopic and electrochemical techniques. The coordination mode of phen ligands was confirmed by single crystal X-ray analysis. The (spectro)electrochemical data show that the first electron transfer in Ru-Pcat takes place on the phen ligand. The emission maxima and quantum yields are strongly affected by the substitution pattern, reaching the far-red region (697 nm) for Ru-3,8P2. The singlet oxygen quantum yields of Ru-Pcat were evaluated using the chemical trapping method. Finally, the photocatalytic performance of Ru-Pcat in the oxidation of sulfides with molecular oxygen was investigated. Both dialkyl and alkyl aryl sulfides were quantitatively transformed into sulfoxides under irradiation with a blue LED in the acetonitrile-water mixture (10 : 1) using a low loading of 0.005-0.05 mol% Ru(II) photocatalysts. To rationalize the effect of phosphonate substituents on the photocatalytic efficiency, comparative kinetic studies of (1) 4-nitrothioanisole oxidation proceeding predominantly via the electron transfer pathway and (2) oxidation of dibutyl sulfide wherein singlet oxygen serves as an oxidant have been performed. It was demonstrated that complexes with the P(O)(OEt)2 substituent at positions 4 and 7 outperform the benchmark photocatalyst Ru-(bpy)3 and the parent complex Ru-phen in the reactions proceeding through electron transfer (reductive quenching photocatalytic cycle). The TON in the oxidation of 4-methoxythioanisole was found to be as high as 1 000 000 that is, to our knowledge, the highest among previously reported photocatalysts. In contrast, upon separating the P(O)(OEt)2 group and the phen core with the 1,4-phenylene linker, singlet oxygen quantum yields significantly increase that favors reactions proceeding through energy transfer (the oxidation of dibutyl sulfide in our case). Thus, both series of Ru(II) complexes prepared in this work are promising for the improvement of known photocatalytic reactions and the development of new transformations.