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A novel synthetic method for enantioselective C2-functionalization of 3-hydroxychromenones promoted by N-heterocyclic carbenes via the formation of α,β-unsaturated acyl azolium intermediates, which occurs with Coates–Claisen rearrangement is established. This synthetic strategy enabled the rapid assembly of enantiomerically enriched δ-hydroxychromenone-derived esters/amides under mild conditions with good to excellent yields and broad substrate scope.

N-Heterocyclic carbenes (NHCs) catalyzing aza-Claisen rearrangement of α,β-unsaturated enals with cyclic vinylogous amides under oxidative conditions generating potentially biologically active dihy...

A novel synthetic method for enantioselective C2-functionalization of 3-hydroxychromenones promoted by N-heterocyclic carbenes

Mycotoxins are toxic metabolites produced by mold fungi, which commonly contaminate cereal crops. These compounds include zearalenone (ZEA), which may disturb the proper functioning of the endocrine system in mammals. The metabolism of ZEA plays a key role in its toxic properties. The type and amount of produced metabolites may contribute to both the reduction and increase in its pathogenic effect. Therefore, it is extremely important to investigate the possible pathways of zearalenone metabolism. The electrochemical approach may prove alternatives for the in vitro and in vivo methods. For this reason, in this study the electrochemical, theoretical and in vitro assays were applied to determine the possible ZEA metabolism mechanism. Electrochemical processes were conducted in the EC/ESI-MS system. The application of HPLC-MS/MS allowed to characterize the obtained electrochemical products specific for phase I and II. Appropriate conditions for redox identification processes were optimized with regard to such parameters as the potential value, mobile phase and working electrode. In addition, the data obtained by instrumental techniques for ZEA metabolism were compared with those obtained by in vitro methods for HepG2 cell lines. Furthermore, results from quantum mechanical calculations allowed to explain the mechanism and the conformational stability of the reduction products.

Magnetic nanoparticles coated with zwitterionic poly(ionic liquid)s were applied for dispersive solid-phase extraction of oligonucleotides. The materials were synthesized by miniemulsion copolymerization of ionic liquids and divinylbenzene on magnetic nanoparticles. The functional monomers contain a positively charged imidazolium ring and one of the anionic groups: derivatives of acetate, malonate, or butyl sulfonate ions. Adsorption of unmodified DNA oligonucleotide on obtained materials was possible in ion-exchange (IE) and hydrophilic interactions (HI) mode. The adsorption in IE was possible at low pH and was almost complete. The adsorption in HI mode required the usage of appropriate addition of organic solvent but did not provide full adsorption. Studies on the desorption of the analytes included determining the impact of ammonium acetate concentration and pH and organic solvents addition on the recovery. The material containing acetic fragments as an anionic group was selected for the final procedure with the use of 10 mM ammonium acetate (pH = 9.5)/methanol (50/50, v/v) as an elution solution. The magnetic dispersive solid-phase extraction procedure was tested for the oligonucleotides with various modifications and lengths. Moreover, it was applied to extract DNA oligonucleotide and its synthetic metabolites from enriched human plasma without any pre-purification, with recoveries greater than 80%.

A new type of hybrid polymeric-based film containing 1-(1,3-diethoxy-1,3-dioxopropan-2-ylo)-3-methylimidazolium bromide (RIL1_Br) and 1-(2-etoxy-2-oxoethyl)-3-methylimidazolium bromide (RIL2_Br) reactive ionic liquids was elaborated. Poly(vinyl alcohol) (PVA)-based films with 9–33 wt % of RILs were subsequently characterized using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and TGA-FTIR. PVA-RIL films were also studied in tensile tests, contact angle and sorption measurements. RIL incorporation enhanced thermal and mechanical stability of PVA membranes due to the hydrogen bonds between RILs and polymer chains. Membrane swelling behavior in water (H2O), ethanol (EtOH), and propan-2-ol (IPA) and the kinetics of water sorption process revealed that PVA-RILs membranes possess the highest affinity towards water. It was pointed out that both the RIL type and the RIL amount in the polymer matrix have significant influence on the membrane swelling behavior and the water sorption kinetics.

N-Heterocyclic carbenes (NHCs) catalyzing aza-Claisen rearrangement of α,β-unsaturated enals with cyclic vinylogous amides under oxidative conditions generating potentially biologically active dihydropyridinone-fused uracils have been developed. This strategy represents a unique NHC-activation-based path with the use of 6-aminouracils as stable α,β-diEWG cyclic vinylogous amides for the efficient synthesis of bicyclic N-unprotected lactams similar to those in many useful drugs.

Three new reactive ionic liquids (RILs) based on the imidazole derivatives were synthesized and used as carriers in polymer inclusion membranes (PIMs) composed of cellulose triacetate (CTA) as a polymer matrix and o–nitrophenyl octyl ether (NPOE) as a plasticizer. The effect of alkyl chain length (C1, C4, and C8) in the imidazolium cation of RILs on the transport and separation properties was evaluated. From among three synthesized RILs only the RIL with the longest alkyl chain (RILC8_Br) can be successfully applied as the carrier for Cd(II) removal from multicomponent aqueous chloride solution containing also Cu(II), Pb(II), and Zn(II) ions. The effects of the stripping phase composition, HCl concentration in the feed solution, and the carrier content in the membrane on the separation performance and transport effectiveness were studied. The results indicate that the RILC8_Br ionic liquid enables selective transport of Cd(II) ions and their active concentration in the stripping solution with the fluxes reaching a value of 2.7 × 10−10 mol/cm2s. In the investigated feed solution concentration range, the selectivity order was found to be Cd(II) > Zn(II) > Pb(II) ≫ Cu(II) and it was independent of the experimental conditions. For a description of the transport kinetics a model similar to the first-order reversible reaction equations was applied and its applicability was proved.

Two novel chiral verbenone-derived triazolium salts have been synthesized from readily available (&minus, )-verbenone and found to be efficient for the enantioselective intramolecular Stetter reaction. The approach, based on the intramolecular annulation between acyl anion equivalents and Michael acceptors, benefits from broad substrate scope, high chemical and stereochemical efficiency, and operational simplicity. Mono-, and disubstituded chromanone derivatives have been obtained in excellent yields and in a highly stereochemical manner.

Cross-linked poly(ionic liquid)s were successfully used for the first time in the preparation of oligonucleotide biological samples. The adsorbents were prepared by co-polymerization of imidazolium-based ionic liquids and divinylbenzene. Consequently, the following three adsorbents were prepared and comprehenzively characterized: poly(3-butyl-1-vinylimidazolium bromide-co-divinylbenzene), poly(3-hexyl-1-vinylimidazolium bromide-co-divinylbenzene) and poly(2-(1-vinylimidazoliumyl)acetate-co-divinylbenzene). Oligonucleotides were adsorbed onto the surface of these materials at low pH values. Preliminary studies of the desorption of the analytes included testing the influence of different types of salts, as well as their concentrations and pH, and organic solvents on the recovery. This allowed for determining the adsorbent and the desorption conditions for further optimization with the use of central composition design. The chosen adsorbent was poly(2-(1-vinylimidazoliumyl)acetate-co-divinylbenzene), and the optimal desorption conditions (5 mM ammonium acetate (pH = 9.5)/methanol (50/50, v/v)) gave a recovery of 99.7 ± 0.3%. The dispersive micro-solid-phase extraction procedure was successfully applied for the extraction of oligonucleotides with various modifications and lengths. Finally, the developed method was used to extract 2′-O-methyl oligonucleotide and its two synthetic metabolites from enriched human plasma without any pre-purification, yielding recoveries over 80%.

A series of novel chiral triazolium salts derived from (−)-β-pinene were synthesized and found to be highly efficient precatalysts for the enantioselective intramolecular Stetter reaction. The triazolium salts prepared from a single precursor, (−)-β-pinene, react with antipodal enantiofacial selectivity in the Stetter reaction to afford mono-, di-, and trisubstituted chromanones in excellent yields with excellent stereoselectivity.

The synthesis of new chiral spirocyclic triazolium salts, derived from (1 S )-fenchone and (1 R )-camphorquinone, are described. These salts, which are N -heterocyclic carbene precatalysts, were successfully employed in the catalytic asymmetric benzoin condensation affording acyloins with good yields and moderate enantioselectivities.

Giving reactions the names of their discoverers is an extraordinary tradition of organic chemistry. Nowadays, this phenomenon is much rarer, although already named historical reactions are still often developed. This is also true in the case of a broad branch of N‑heterocyclic carbenes catalysis. NHCs allow many unique synthetic paths, including commonly known name reactions. This article aims to gather this extensive knowledge and compare historical reactions with current developed processes. Furthermore, this review is a great opportunity to highlight some of the unique applications of these procedures in the total synthesis of biologically active compounds. Hence, this concise article may also be a source of knowledge for scientists just starting their adventure with N‑heterocyclic carbene chemistry.

In the present work, gold electrodes were modified using a redox-active layer based on dipyrromethene complexes with Cu(II) or Co(II) and a dipodal anion receptor functionalized with dipyrromethene. These modified gold electrodes were then applied for the electrochemical detection of anions (Cl–, SO42–, and Br–) in a highly diluted water solution (in the picomolar range). The results showed that both systems, incorporating Cu(II) as well as Co(II) redox centers, exhibited highest sensitivity toward Cl–. The selectivity sequence found for both systems was Cl– > SO42– > Br–. The high selectivity of Cl– anions can be attributed to the higher binding constant of Cl– with the anion receptor and the stronger electronic effect between the central metal and anion in the complex. The detection limit for the determination of Cl– was found at the 1.0 pM level for both sensing systems. The electrodes based on Co(II) redox centers displayed better selectivity toward Cl– anion detection than those based on Cu(II) cente...

New (1R)-camphor-derived triazolium salts, incorporating a spirocyclic system, are described. Benzoin condensation of aromatic aldehydes, mediated by these salts affords α-hydroxyketones in good yields and moderate enantiomeric excesses.

Novel chiral N-heterocyclic carbenes derived from (−)-β-pinene have been synthesized and used as efficient catalysts for the intramolecular Stetter reaction. Mono-, di-, and trisubstituted 4-chromanone derivatives have been obtained almost quantitatively and with high enantioselectivity up to 99:1 er.

A highly efficient and enantioselective approach to the synthesis of functionalized benzofuran-3(2H)-ones is presented. It proceeds via an intramolecular Stetter reaction using &beta, &beta, disubstituted Michael acceptors in the construction of five-membered rings with fully-substituted quaternary stereogenic centers and is promoted by terpene-derived triazolium salts. As a result, a series of chiral 2,2-disubstituted benzofuran-3(2H)-one derivatives with linear, branched, and cyclic aliphatic substitutions on the quaternary stereogenic center were obtained in high yields and with excellent enantioselectivities of up to 99% ee.

The synthesis of new chiral spirocyclic triazolium salts, derived from (1 S )-fenchone and (1 R )-camphorquinone, are described. These salts, which are N -heterocyclic carbene precatalysts, were successfully employed in the catalytic asymmetric benzoin condensation affording acyloins with good yields and moderate enantioselectivities.

We report the synthesis of chiral ferrocenyl selenides of general formula: Fe(C5H4SeR*)(C5H5) and Fe(C5H4SeR*)2 where R* = neomenthyl and cis-myrtanyl. The title compounds have been obtained by the straightforward reaction of 1,1′-dilithioferrocene-TMEDA adduct with either (+)-dineomenthyl diselenide or (−)-bis(cis-myrtanyl) diselenide. We also report herein on the X-ray crystal structure of known 1,1′-bis(phenylseleno)ferrocene, Fe(C5H4SePh)2. All newly-obtained derivatives were characterized by 1H and 13C NMR, mass spectra and elemental analyses.

Photoredox pairs consisting of selenocarbocyanine dye cations and phenyltrialkylborate anions were employed as the novel, effective visible-wavelength initiators of the radical polymerization of acrylic monomer. The influence of the sensitizers and electron donor structure on the photopolymerization kinetics of multiacrylate monomer was investigated by photo-DSC. It was found that the polymerization rate and the final conversion degree were dependent on both dye and borate structure. The kinetic studies of the free radical polymerization revealed an increase in the polymerization rate with a decrease of the borate oxidation potentials which was additionally reflected by the linear relationship between the Hammett constant and rate of polymerization. The efficiency of these initiators was discussed on the basis of the free energy change for electron transfer from an excited cyanine dye cation to a borate anion. The Δ G el values were estimated for photoredox pairs containing a series of phenyltrialkylborate anions and one selenocarbocyanine dye cation. The relationship between the rate of polymerization and the free energy of activation for electron transfer reaction gives the dependence predicted by the classical theory of electron transfer. The photoreduction of cyanine phenyltrialkylborate complex was studied using nanosecond laser flash photolysis. The dye triplet was found to be quenched by the electron donors via an electron transfer process. Rate constants ( k q ) for the quenching of the excited states were high and approached diffusion-controlled limits and were found to depend on the borate structure.

N-heterocyclic carbene organocatalysis under oxidizing conditions provides a vast range of various synthetic procedures via diverse mechanisms. The available catalysts, bases, oxidants, and oxidizing methods afford numerous opportunities for developing this branch of organocatalysis. Furthermore, implementation of tandem reactions and cooperative catalysis in the described methodology significantly expands the possibilities of modern organic chemistry. This approach allows the synthesis of different structurally complex and often enantiomerically enriched substances, which can be interesting in terms of biological activity and natural product synthesis. Many esters, amides, thioesters, lactams, lactones, and other cyclic compounds obtained in oxidative or oxygenative reactions promoted by N-heterocyclic carbenes can be interesting precursors in advanced organic synthesis. Sophistication and broad applicability prove that the described synthetic approaches are exceptionally worthy of further development.

A convenient method for the synthesis of optically active dialkyl diselenides derived from bicyclic terpenes functionalized with hydroxy, etheral, sulfide, and selenide groups is described. The diselenides were used for a synthesis of chiral electrophilic selenium reagents, then in the asymmetric selenenylation of styrene and selenocyclization with o-allylphenol. The influence of nonbonding selenium-heteroatom interactions in the generated organoselenium electrophiles on the stereoselectivity of an addition reaction has been investigated. Calculations by a DFT method on a B3LYP (6–311G (d)) level, confirmed the existence of nonbonded selenium–heteroatom interactions in the investigated systems.

A convenient method for the synthesis of optically active trans-hydroxyselenides and trans-hydroxydiselenides from the bicyclic terpene group based on the reactions of sodium selenide or sodium diselenide with cis- and trans-(+)-3-carane, trans-(+)-2-carane and (−)-β-pinane epoxides is described. The corresponding cis-hydroxy and cis-methoxydiselenides were obtained in the reaction of sodium diselenide with β-hydroxy- and β-methoxytosylates. The influence of a hydroxy group at the β-position on the diastereomeric ratio of the products of the asymmetric methoxyselenenylation of styrene has been established by composition of the products, crystal structure analyses, and theoretical calculations using a DFT method on the B3LYP level (6-311G(d)).

Six diselenides have been evaluated as novel photoinitiators for free radical polymerization induced with an argon-ion laser irradiation. Our studies show that the rate of photopolymerization depends on the structure and concentration of the photoinitiators. The relation between the rate of polymerization and the light intensity shows a linear dependence.

In many settings, molecular testing is needed but unavailable due to complexity and cost. Simple, rapid, and specific DNA detection technologies would provide important alternatives to existing detection methods. Here we report a novel, rapid nucleic acid detection method based on the accelerated photobleaching of the light-sensitive cyanine dye, 3,3'-diethylthiacarbocyanine iodide (DiSC(2)(3) I(-)), in the presence of a target genomic DNA and a complementary peptide nucleic acid (PNA) probe. On the basis of the UV-vis, circular dichroism, and fluorescence spectra of DiSC(2)(3) with PNA-DNA oligomer duplexes and on characterization of a product of photolysis of DiSC(2)(3) I(-), a possible reaction mechanism is proposed. We propose that (1) a novel complex forms between dye, PNA, and DNA, (2) this complex functions as a photosensitizer producing (1)O(2), and (3) the (1)O(2) produced promotes photobleaching of dye molecules in the mixture. Similar cyanine dyes (DiSC(3)(3), DiSC(4)(3), DiSC(5)(3), and DiSC(py)(3)) interact with preformed PNA-DNA oligomer duplexes but do not demonstrate an equivalent accelerated photobleaching effect in the presence of PNA and target genomic DNA. The feasibility of developing molecular diagnostic assays based on the accelerated photobleaching (the smartDNA assay) that results from the novel complex formed between DiSC(2)(3) and PNA-DNA is under way.

A convenient route for the synthesis of optically active dialkyl diselenides from the p-menthane system utilizing a reaction of alkyl tosylates and chlorides with sodium diselenide is reported. The diselenides obtained have been used for asymmetric methoxyselenenylation of styrene. Quantum chemical calculations of the chair conformers stability of the terpeneselenenyl bromides from the p-menthane group have also been carried out using density functional theory (DFT, at the B3LYP/6-311G(d) level). The influence of the diselenides structure on the stereoselectivity in the methoxyselenenylation reaction is also discussed.

Selenocyclization with the use of the monoterpene diselenides from menthane, carane and pinane groups has been studied. The conditions for asymmetric selenocyclization have been optimized. It has been established that the best enantiomeric excesses were obtained in the case of selenocyclization for the unsubstituted alkyl diselenides with (+)-dineomenthyl diselenide. The results of the selenocyclization of the (+)-dineomenthyl diselenide with the unsaturated alcohols and acids are presented.

A catalytic asymmetric intramolecular crossed-benzoin reaction for the synthesis of chromanones by novel camphor-derived N-heterocyclic carbenes is described. The corresponding chromanones bearing quaternary stereogenic centers were isolated in high yields with high to excellent enantioselectivity.

A catalytic asymmetric intramolecular crossed-benzoin reaction for the synthesis of chromanones by novel camphor-derived N-heterocyclic carbenes is described. The corresponding chromanones bearing quaternary stereogenic centers were isolated in high yields with high to excellent enantioselectivity.

New (1R)-camphor-derived triazolium salts, incorporating a spirocyclic system, are described. Benzoin condensation of aromatic aldehydes, mediated by these salts affords α-hydroxyketones in good yields and moderate enantiomeric excesses.

The reaction of sodium diselenide with optically active alkyl tosylates or chlorides is found to be a useful method for the synthesis of optically active dialkyl diselenides. Optically active monoterpene diselenides derived from menthane, carane, pinane, and bornane systems have been obtained. The influence of the terpene fragment of the obtained diselenides on the diastereomeric excess of the methoxyselenylation products has been investigated. The best result for methoxyselenylation was observed for (–)-diisopinocamphyl diselenide. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The relative configurations of four stereogenic centers of the C33-C42 fragment of niphimycin A were assigned as 2S*, 3R*, 4S* and 6S*, based upon (1)H NMR analysis with double-quantum filtered COSY and nuclear Overhauser spectroscopy experiments. These data were then correlated with absolute configurations at C36 and C38 of niphimycin A, which were declared previously as 36S and 38S [3]. This allowed for the assignment of the absolute configurations at C34 and C35 of niphimycin A as 34S and 35R.

The relative configurations of four stereogenic centers of the C33-C42 fragment of niphimycin A were assigned as 2S*, 3R*, 4S* and 6S*, based upon (1)H NMR analysis with double-quantum filtered COSY and nuclear Overhauser spectroscopy experiments. These data were then correlated with absolute configurations at C36 and C38 of niphimycin A, which were declared previously as 36S and 38S [3]. This allowed for the assignment of the absolute configurations at C34 and C35 of niphimycin A as 34S and 35R.