Optically Pure Calixarenyl Phosphine via Stereospecific Alkylation on Evans' Oxazolidinone Moiety.

A convenient protocol for the synthesis of 25,26,27-tribenzoyl-28-[((S)-1-diphenylphos- phanyl-propan-2-yl)oxy]-calix[4]arene via stereospecific methylation on Evans' oxazolidinone moiety was reported. According to the 13C NMR analysis of this phosphine, the calix[4]arene skeleton adopted a 1,3-alternate conformation. The latter conformation of the macrocycle and the (S)-chirality of the carbon atom bearing the methyl substituent were confirmed by a single-crystal X-ray diffraction study. After coordination of the phosphinated ligand to the dimeric [RuCl2(p-cymene)]2 organometallic precursor, the resulting arene-ruthenium complex was tested in the asymmetric reduction of acetophenone and alcohol was obtained with modest enantiomeric excess.

Hydrogenation Versus Hydrosilylation: The Substantial Impact of a Palladium Capsule on the Catalytic Outcome.

A palladium capsule, made of three cavitands, namely P,P-dichlorido{5,17-bis[5-(diphenylphosphanyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetrapentylresorcin[4]arenyl-17-oxymthyl]-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetrapentylresorcin[4]arene}palladium(II) (1), was synthetized by coordination of the corresponding diphosphinated ligand and the palladium precursor [PdCl2(PhCN)2] in 27% yield. The obtained P,P-chelate complex was fully characterized by elemental analysis, NMR and mass spectrometry. Molecular dynamics simulations carried out on the metallo-capsule showed the structure made by the three cavitands was slightly distorted over the 1 µs of the simulation. The evaluation of the palladium capsule 1 in the reaction between arylacetylenes and Et3SiH in undried conditions unequivocally demonstrates a drastic change in chemoselectivity, with the formation of the partially hydrogenation product rather than the hydrosilylation products observed with complexes whose active center is more accessible, for instance [PdCl2(PPh3)2].

Design, synthesis, antimicrobial activity and molecular docking study of cationic bis-benzimidazole-silver(I) complexes.

Two series of bis(1-alkylbenzimidazole)silver(I) nitrate and bis(1-alkyl-5,6-dimethylbenzimidazole)silver(I) nitrate complexes, in which the alkyl substituent is either an allyl, a 2-methylallyl, an isopropyl or a 3-methyloxetan-3-yl-methyl chain, were synthesized and fully characterized. The eight N-coordinated silver(I) complexes were screened for both antimicrobial activities against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii) and Gram-positive (Staphylococcus aureus, Staphylococcus aureus MRSA, and Enterococcus faecalis) bacteria and antifungal activities against Candida albicans and Candida glabrata strains. Moderate minimal inhibitory concentrations (MIC) of 0.087 µmol/mL were found when the Gram-negative and Gram-positive bacteria were treated with the silver complexes. Nevertheless, MIC values of 0.011 µmol/mL, twice lower than for the well-known fluconazole, against the two fungi were measured. In addition, molecular docking was carried out with the structure of Escherichia coli DNA gyrase and CYP51 from the pathogen Candida glabrata with the eight organometallic complexes, and molecular reactivity descriptors were calculated with the density functional theory-based calculation methods.

Encapsulated Neutral Ruthenium Catalyst for Substrate-Selective Oxidation of Alcohols.

The neutral complex dichloro-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)-(4-trifluoro-methylphenyl)methyl]phosphonate} (p-cymene)-ruthenium(II) was encapsulated inside a self-assembled hexameric host obtained upon reaction of 2,8,14,20-tetra-undecyl-resorcin[4]arene and water. The formation of an inclusion complex was inferred from a combination of spectral measurements (MS, UV/Vis spectroscopy, 1 H and DOSY NMR). The 31 P and 19 F NMR spectra are consistent with motions of the ruthenium complex inside the self-assembled capsule. Molecular dynamics simulations carried out on the inclusion complex confirmed these intra-cavity movements and highlighted possible supramolecular interactions between the ruthenium first coordination sphere ligands and the inner part (aromatic rings) of the capsule. The embedded ruthenium complex was assessed in the catalytic oxidation (using NaIO4 as oxidant) of mixtures of three arylmethyl alcohols into the corresponding aldehydes. The reaction kinetics were shown to vary as a function of the substrates' size, with the oxidation rate varying in the order benzylalcohol >4-phenyl-benzylalcohol >9-anthracenemethanol. Control experiments realized in the absence of hexameric capsule did not allow any discrimination between the substrates.

Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities.

Two silver(I) complexes, bis{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3:κN4-amino) (4-trifluoromethylphenyl)methyl]phosphonate-(tetrafluoroborato-κF)}-di-silver(I) and tetrakis-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-κN3-amino)(4-trifluoromethylphenyl)methyl]phosphonate} silver(I) tetrafluoroborate, were prepared starting from the diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-amino)(4-trifluoromethylphenyl)methyl]phosphonate (1) ligand and AgBF4 salt in Ag/ligand ratios of 1/1 and 1/4, respectively. The structure, stoichiometry, and geometry of the silver complexes were fully characterized by elemental analyses, infrared, single-crystal X-ray diffraction studies, multinuclear NMR, and mass spectroscopies. The binuclear complex ([Ag2(1)2(BF4)2]; 2) crystallizes in the monoclinic asymmetric space group P21/c and contains two silver atoms adopting a {AgN2F} planar trigonal geometry, which are simultaneously bridged by two oxadiazole rings of two ligands, while the mononuclear complex ([Ag(1)4]BF4; 3) crystallizes in the non-usual cubic space group Fd-3c in which the silver atom binds to four distinct electronically enriched nitrogen atoms of the oxadiazole ring, in a slightly distorted {AgN4} tetrahedral geometry. The α-aminophosphonate and the monomeric silver complex were evaluated in vitro against MCF-7 and PANC-1 cell lines. The silver complex is promising as a drug candidate for breast cancer and the pancreatic duct with half-maximal inhibitory concentration (IC50) values of 8.3 ± 1.0 and 14.4 ± 0.6 µM, respectively. Additionally, the interactions of the ligand and the mononuclear complex with Vascular Endothelial Growth Factor Receptor-2 and DNA were evaluated by molecular docking methods.

Cracking cavitands: metal-directed scission of phosphinyl-substituted resorcinarenes.

Resorcinarene-derived tetramethylene cavitands bearing a diphenylphosphino group grafted to their wider rim undergo facile, directed C-O bond breaking upon reaction with transition-metal ions in the presence of nucleophiles. One possible reaction mechanism involves formation of a P,O-chelate complex, which weakens the adjacent O-CH2 bond, leading to the formation of an oxacarbenium intermediate.

Confining phosphanes derived from cyclodextrins for efficient regio- and enantioselective hydroformylation.

Two confining phosphane ligands derived from either α- or ß-cyclodextrin produce singly P(III) -ligated metal complexes with unusual coordination spheres. High-pressure NMR studies have revealed that rhodium hydride complexes of the same type are also formed under hydroformylation conditions. This unique feature strongly favors the formation of the branched aldehyde at the expense of the linear one with high enantioselectivity in the rhodium-catalyzed hydroformylation of styrene.

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon-carbon bond forming reactions.

The capacity of two cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate exclusively singly phosphorus-ligated complexes, in which the cyclodextrin cavity tightly wraps around the metal centre, was explored with a number of late transition metal cations. Both cyclodextrin-derived ligands were assessed in palladium-catalysed Mizoroki-Heck coupling reactions between aryl bromides and styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of styrene on the other hand. The inability of both chiral ligands to form standard bis(phosphine) complexes under catalytic conditions was established by high-pressure NMR studies and shown to have a deep impact on the two carbon-carbon bond forming reactions both in terms of activity and selectivity. For example, when used as ligands in the rhodium-catalysed hydroformylation of styrene, they lead to both high isoselectivity and high enantioselectivity. In the study dealing with the Mizoroki-Heck reactions, comparative tests were carried out with WIDEPHOS, a diphosphine analogue of HUGPHOS-2.

Resorcin[4]arene-derived mono-, bis- and tetra-imidazolium salts as ligand precursors for Suzuki-Miyaura cross-coupling.

Eleven resorcinarene cavitands bearing either one, two or four (3-R-1-imidazolylium)-methyl substituents (R = (n)Bu, Ph, Mes, (i)Pr(2)C(6)H(3)) anchored at resorcinolic "ortho" positions have been synthesised from the appropriate bromomethylated precursor. Combining the imidazolium salts with palladium acetate and Cs(2)CO(3) gave active Suzuki-Miyaura cross coupling catalysts. The highest activities were observed with the doubly functionalised cavitands, which all have the imidazolylium groups attached to proximal resorcinol units.

Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus.

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540-1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses.

Cavity-shaped ligands: calix[4]arene-based monophosphanes for fast Suzuki-Miyaura cross-coupling.

Five conical calix[4]arenes that have a PPh(2) group as the sole functional group anchored at their upper rim were assessed in palladium-catalysed cross-coupling reactions of phenylboronic acid with aryl halides (dioxane, 100 degrees C, NaH). With arylbromides, remarkably high activities were obtained with the catalytic systems remaining stable for several days. The performance of the ligands is comparable to a Buchwald-type triarylphosphane, namely, (2'-methyl[1,1'-biphenyl]-2-yl)diphenylphosphane, which in contrast to the calixarenyl phosphanes tested may display chelating behaviour in solution. With the fastest ligand, 5-diphenylphosphanyl-25,26,27,28-tetra(p-methoxy)benzyloxy-calix[4]arene (8), the reaction turnover frequency for the arylation of 4-bromotoluene was 321,000 versus 214,000 mol(ArBr).mol(Pd)(-1).h(-1) for the reference ligand. The calixarene ligands were also efficient in Suzuki cross-coupling reactions with aryl chlorides. Thus, by using 1 mol% of [Pd(OAc)(2)] associated with one of the phosphanes, full conversion of the deactivated arenes 4-chloroanisole and 4-chlorotoluene was observed after 16 h. The high performance of the calixarenyl-phosphanes in Suzuki-Miyaura coupling of aryl bromides possibly relies on their ability to stabilise a monoligand [Pd(0)L(ArBr)] species through supramolecular binding of the Pd-bound arene inside the calixarene cavity.

High-pressure investigations under CO/H2 of rhodium complexes containing hemispherical diphosphites.

The two rhodium complexes [Rh(acac)(L(R))] (L(R)=(S,S)-5,11,17,23-tetra-tert-butyl-25,27-di(OR)-26,28-bis(1,1'-binaphthyl-2,2'-dioxyphosphanyloxy)calix[4]arene; 6: R=benzyl, 7: R=fluorenyl), each based on a hemispherical chelator forming a pocket about the metal centre upon chelation, are active in the hydroformylation of 1-octene and styrene. As expected for this family of diphosphanes, both complexes resulted in remarkably high selectivity towards the linear aldehyde in the hydroformylation of 1-octene (l/b≈15 for both complexes). Linear aldehyde selectivity was also observed when using styrene, but surprisingly only 6 displayed a marked preference for the linear product (l/b=12.4 (6) vs. 1.9 (7)). A detailed study of the structure of the complexes under CO or CO/H(2) in toluene was performed by high-pressure NMR (HP NMR) and FT-IR (HP-IR) spectroscopies. The spectroscopic data revealed that treatment of 6 with CO gave [Rh(acac)(CO)(η(1)-L(benzyl))] (8), in which the diphosphite behaves as a unidentate ligand. Subsequent addition of H(2) to the solution resulted in a well-defined chelate complex with the formula [RhH(CO)(2)(L(benzyl))] (9). Unlike 6, treatment of complex 7 with CO only led to ligand dissociation and concomitant formation of [Rh(acac)(CO)(2)], but upon addition of H(2) a chelate complex analogous to 9 was formed quantitatively. In both [RhH(CO)(2)(L(R))] complexes the diphosphite adopts the bis-equatorial coordination mode, a structural feature known to favour the formation of linear aldehydes. As revealed by variable-temperature NMR spectroscopy, these complexes show the typical fluxionality of trigonal bipyramidal [RhH(CO)(2)(diphosphane)] complexes. The lower linear selectivity of 7 versus 6 in the hydroformylation of styrene was assigned to steric effects, due to the pocket in which the catalysis takes place being less adapted to accommodate CO or larger olefins and, therefore, possibly leading to facile ligand decoordination. This interpretation was corroborated by an X-ray structure determination carried out for 7.

Synthesis of a resorcinarene-based tetraphosphine-cavitand and its use in Heck reactions.

A resorcinarene cavitand substituted by four -CH(2)PPh(2) pendant arms was synthesised starting from a generic C(5)-resorcinarene. Combining this tetraphosphine with palladium acetate and Cs(2)CO(3) gave an active Heck catalyst. The highest activities were observed by using a tetraphosphine/Pd ratio of ca. 1:1.

Calix[4]arene-fused phospholes.

An upper rim, o-(diphenylphosphinyl)phenyl-substituted calix[4]arene has been prepared and its coordinative properties investigated. When heated in the presence of palladium, the new biarylphosphine undergoes conversion into two diastereomeric, calixarene-fused phospholes. In both, the P lone pair adopts a fixed orientation with respect to the calixarene core. The more hindered phosphole (8), i.e. the one with the endo-oriented lone pair (cone angle 150°-175°), forms complexes having their metal centre positioned very near the calixarene unit but outside the cavity, thus inducing an unusual chemical shift of one of the methylenic ArCH2Ar protons owing to interactions with the metal centre. As expected for dibenzophospholes, the complex [Rh(acac)(CO)·8], when combined with one equivalent of free 8, efficiently catalyses the hydroformylation of styrene, the catalytic system displaying high regioselectivity in favour of the branched aldehyde (b/l ratio up to 30). The optical and redox properties of the derivatives have also been investigated.

Alkene metathesis catalysis in ionic liquids with ruthenium allenylidene salts.

Ring closing metathesis of dienes in 1-butyl-3-methylimidazolium salts in the presence of ruthenium allenylidene salts as catalyst is described.

Tandem isomerization/Claisen transformation of allyl homoallyl and diallyl ethers into gamma,delta-unsaturated aldehydes with a new three component catalyst Ru3(CO)12/imidazolinium salt/Cs2CO3.

The three component catalyst Ru3(CO)12/1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride/Cs2CO3 (molar ratio 1:3:6) successively promotes both allyl to vinyl isomerization and Claisen rearrangement from allyl homoallyl and diallyl ethers to selectively afford gamma,delta-unsaturated aldehydes.

High efficiency of cavity-based triaryl-phosphines in nickel-catalysed Kumada-Tamao-Corriu cross-coupling.

Combining diaryl-calixarenyl phosphines with [Ni(cod)(2)] resulted in highly active Kumada-Tamao-Corriu cross-coupling catalysts. With one of the ligands, TOFs up to 439,000 mol(ArBr) mol(Ni)(-1) h(-1) were observed in the reaction of 1-bromonaphthalene with PhMgBr. The systems were also found to be active at room temperature with aryl chlorides.

Infinite terbium(III) chains formed from a tetra-phosphorylated resorcinarene cavitand.

Reaction of [Tb(III)(DMSO)(8)](CF(3)SO(3))(3) with a resorcinarene cavitand substituted by four -CH(2)P(O)Ph(2) pendant arms afforded an infinite 1D inorganic polymer, in which the consecutive resorcinarene units are linked through two terbium strands, this connection involves pairs of phosphoryl groups occupying adjacent positions of the resorcinarene units.

Supramolecular chemistry of fluoroanions: selectivity in weak interactions.

Interactions of a chiral, calixarene-based cationic Pd(II) catalyst with [BF(4)](-) and [PF(6)](-) anions have very different consequences, association with the former giving rise to capsule formation.