Andrea Baschieri

Catalytic Asymmetric Conjugate Addition of Nitroalkanes to 4‐Nitro‐5‐styrylisoxazoles

The conjugate addition of nitroalkanes to activated alkenes is a useful reaction that involves the formation of a new C C bond and the installation of an aliphatic nitro group: a precursor of an amine, a ketone, or a carboxylate. Several catalytic asymmetric variants of this transformation have been reported for alkenes that act as soft electrophiles. However, reported methods are not suitable for a,bunsaturated esters or acids, such as cinnamates, which are poor substrates in catalytic enantioselective Michael reactions. This experimental finding is justified by the electrophilic nature of cinnamates, which is not well-matched with soft nitroalkane nucleophiles. Additionally, since the carbonyl group of cinnamates does not establish well-defined interactions with commonly used catalysts (e.g. amines or chiral Lewis acid complexes), an efficient transfer of chirality from the catalyst to the substrate is problematic. To overcome these problems, various a,b-unsaturated carbonyl compounds have been used in catalytic enantioselective Michael reactions to give products in which the desired carboxylates could be unveiled in a subsequent step. Notable examples of such compounds include chalcones, enals, a’-hydroxyenones, alkylidene malonates, and alkenoyl pyrazoles and pyrroles. We have developed styrylisoxazoles 1 as cinnamate equivalents that show high reactivity towards stabilized (soft) nucleophiles. Compounds 1 are stable solids that can be obtained in large quantities (10–100 mmol) as single E isomers through the reaction of commercially available 3,5dimethyl-4-nitroisoxazole with an aromatic or heteroaromatic aldehyde. We previously described efficient Michael addition reactions of compounds 1 with soft nucleophiles, such as enolates, nitroalkanes, and indoles. The 4-nitroisoxazol-5-yl core present in adducts 2 (Scheme 1) could be opened to display a carboxylic acid by a reaction described by SartiFantoni and co-workers: an operationally simple procedure involving the treatment of 4-nitroisoxazoles with excess aqueous NaOH. Therefore, compounds 1 constitute a valuable synthetic alternative to cinnamic esters in procedures that require tuning of the acceptor electrophilicity. We now report the use of compounds 1 in catalytic asymmetric settings in combination with phase-transfer catalysis (PTC) and the use of the resulting adducts 2 for the preparation of g-nitroesters 3 and g-amino acids 4. The high enantioselectivity observed when the reactions were carried out at room temperature with a low catalyst loading (2–5 mol%), the compatibility of nitromethane as well as secondary and tertiary nitroalkanes with the reaction conditions, and the unusual diastereocontrol when secondary nitroalkanes were used, are advantages of this process over many other procedures in which a,b-unsaturated carboxylic acid analogues are used. As the substrate and catalyst could be prepared in one step from inexpensive starting materials, the procedure is also practical to execute. We initially treated the styrylisoxazole 1a with nitromethane (5 equiv) in the presence of various inorganic bases in suitable organic solvents. This study identified solid K2CO3 and toluene as the most suitable combination of a base and a solvent. Having identified suitable reaction conditions, we tested a range of quaternary ammonium salts derived from cinchona alkaloids as catalysts (Table 1). Use of the Scheme 1. Catalytic asymmetric conjugate addition of nitroalkanes to 4-nitro-5-styrylisoxazoles 1 and synthetic applications of Michael adducts 2.

A synergic nanoantioxidant based on covalently modified halloysite–trolox nanotubes with intra-lumen loaded quercetin

We describe the preparation and properties of the first example of a synergic nanoantioxidant, obtained by different functionalizations of the external surface and the inner lumen of halloysite nanotubes (HNTs). Trolox, a mimic of natural α-tocopherol, was selectively grafted on the HNT external surface; while quercetin, a natural polyphenolic antioxidant, was loaded into the inner lumen to afford a bi-functional nanoantioxidant, HNT-Trolox/Que, which was investigated for its reactivity with transient peroxyl radicals and a persistent 1,1-diphenyl-2-picrylhydrazyl (DPPH˙) radical in comparison with the corresponding mono-functional analogues HNT-Trolox and HNT/Que. Both HNT-Trolox and HNT/Que showed good antioxidant performance in the inhibited autoxidation of organic substrates; however HNT-Trolox/Que protection by reaction with peroxyl radicals was 35% higher in acetonitrile and 65% in chlorobenzene, as compared to the expected performance based on the sum of contributions of NHT-Trolox and NHT/Que. Similar enhancement was observed also in the trapping of DPPH˙ radicals. Synergism between the distinct antioxidant functions was based on the rapid reaction of externally exposed Trolox (rate constant with peroxyl radicals was 1.1 × 106 M-1 s-1 and 9 × 104 M-1 s-1 respectively in chlorobenzene and acetonitrile, at 30 °C), followed by its regeneration by quercetin released from the HNT lumen. The advantages of this novel nanoantioxidant are discussed.

Peroxyl Radical Reactions in Water Solution: A Gym for Proton-Coupled Electron-Transfer Theories.

The reactions of alkylperoxyl radicals with phenols have remained difficult to investigate in water. We describe herein a simple and reliable method based on the inhibited autoxidation of water/THF mixtures, which we calibrated against pulse radiolysis. With this method we measured the rate constants kinh for the reactions of 2-tetrahydrofuranylperoxyl radicals with reference compounds: urate, ascorbate, ferrocenes, 2,2,5,7,8-pentamethyl-6-chromanol, Trolox, 6-hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid, 2,6-di-tert-butyl-4-methoxyphenol, 4-methoxyphenol, catechol and 3,5-di-tert-butylcatechol. The role of pH was investigated: the value of kinh for Trolox and 4-methoxyphenol increased 11- and 50-fold from pH 2.1 to 12, respectively, which indicate the occurrence of a SPLET-like mechanism. H(D) kinetic isotope effects combined with pH and solvent effects suggest that different types of proton-coupled electron transfer (PCET) mechanisms are involved in water: less electron-rich phenols react at low pH by concerted electron-proton transfer (EPT) to the peroxyl radical, whereas more electron-rich phenols and phenoxide anions react by multi-site EPT in which water acts as proton relay.

A new tetraarylcyclopentadienone based low molecular weight gelator: synthesis, self-assembly properties and anion recognition

A new class of tetraarylcyclopentadienones bearing 3-hydroxy-1-propynyl substituents has been synthesized. One of them, 3,4-bis (4-(3-hydroxy-3-methylbut-1-ynyl) phenyl)-2,5-diphenylcyclopenta-2,4-dienone, exhibits pronounced aggregation properties in various organic solvents responding to thermal and ultrasound stimuli and represents the first example of a tetraarylcyclopentadienone based low molecular weight organogelator. The hydroxydimethyl group on the ethynyl substituent proved to be essential to perform the gelation process. The 1H NMR analysis and FT-IR spectroscopy suggested that the intermolecular π–π and hydrogen bonding interactions of the gelator with the solvent are the main driving forces for the supramolecular assembly. The SEM images of xerogels show the characteristic gelation morphologies of 3D fibrous network structures. Fluorescence and UV/Vis absorption studies provided more information to define the molecular packing model in the gelation state. In addition the obtained gels show selective response to the fluoride anion.

A Mesoionic Carbene as Neutral Ligand for Phosphorescent Cationic Ir(III) Complexes.

Two phosphorescent Ir(III) complexes bearing a mesoionic carbene ligand based on 1,2,3-triazolylidene are obtained for the first time. A silver-iridium transmetalation of the in situ-generated mesoionic carbene affords the cationic dichloro complex [Ir(trizpy)2Cl2](+) (3, trizpy = 1-benzyl-3-methyl-4-(pyridin-2-yl)-1H-1,2,3-triazolylidene) that reacts with a bis-tetrazolate (b-trz) dianionic ligand to give [Ir(trizpy)2(b-trz)](+) (5). The new compounds are fully characterized by NMR spectroscopy and mass spectrometry, and the X-ray structure of 3 is determined. The electrochemical behavior is somewhat different compared to most standard cationic iridium complexes. The first oxidation process is shifted to substantially higher potential in both 3 and 5, due to peculiar and different ligand-induced effects in the two cases, which stabilize the highest occupied molecular orbital; reduction processes are centered on the mesoionic carbene ligands. Both compounds exhibit a mostly ligand-centered luminescence band in the blue-green spectral region, substantially stronger in the case of 5 versus 3, both in CH3CN solution and in poly(methyl methacrylate) matrix at room temperature. Optimized geometries, orbital energies, spin densities, and electronic transitions are determined via density functional theory calculations, which support a full rationalization of the electrochemical and photophysical behavior. This work paves the way for the development of Ir-based emitters with neutral mesoionic carbene ligands and anionic ancillary ligands, a new concept in the area of cationic Ir(III) complexes.

Acid Is Key to the Radical-Trapping Antioxidant Activity of Nitroxides

Persistent dialkylnitroxides (e.g., 2,2,6,6-tetramethylpiperidin-1-oxyl, TEMPO) play a central role in the activity of hindered amine light stabilizers (HALS)-additives that inhibit the (photo)oxidative degradation of consumer and industrial products. The accepted mechanism of HALS comprises a catalytic cycle involving the rapid combination of a nitroxide with an alkyl radical to yield an alkoxyamine that subsequently reacts with a peroxyl radical to eventually re-form the nitroxide. Herein, we offer evidence in favor of an alternative reaction mechanism involving the acid-catalyzed reaction of a nitroxide with a peroxyl radical to yield an oxoammonium ion followed by electron transfer from an alkyl radical to the oxoammonium ion to re-form the nitroxide. In preliminary work, we showed that TEMPO reacts with peroxyl radicals at diffusion-controlled rates in the presence of acids. Now, we show that TEMPO can be regenerated from its oxoammonium ion by reaction with alkyl radicals. We have determined that this reaction, which has been proposed to be a key step in TEMPO-catalyzed synthetic transformations, occurs with k ∼ 1-3 × 10(10) M(-1) s(-1), thereby enabling it to compete with O2 for alkyl radicals. The addition of weak acids facilitates this reaction, whereas the addition of strong acids slows it by enabling back electron transfer. The chemistry is shown to occur in hydrocarbon autoxidations at elevated temperatures without added acid due to the in situ formation of carboxylic acids, accounting for the long-known catalytic radical-trapping antioxidant activity of TEMPO that prompted the development of HALS.

Explaining the antioxidant activity of some common non-phenolic components of essential oils

Limonene, linalool and citral are common non-phenolic terpenoid components of essential oils, with attributed controversial antioxidant properties. The kinetics of their antioxidant activity was investigated using the inhibited autoxidation of a standard model substrate. Results indicate that antioxidant behavior of limonene, linalool and citral occurs by co-oxidation with the substrate, due to very fast self-termination and cross-termination of the oxidative chain. Rate constants kp and 2kt, (M-1s-1) at 30°C were 4.5 and 3.5×106 for limonene, 2.2 and 9.0×105 for linalool and 39 and 1.0×108 for citral. Behavior is bimodal antioxidant/pro-oxidant depending on the concentration. Calculations at the M05/6-311+g(2df,2p) level indicate that citral reacts selectively at the aldehyde C-H having activation enthalpy and energy respectively lower by 1.3 and 1.8kcal/mol compared to the most activated allyl position. Their termination-enhancing antioxidant chemistry might be relevant in food preservation and could be exploited under appropriate settings.

Anionic Cyclometalated Iridium(III) Complexes with a Bis-Tetrazolate Ancillary Ligand for Light-Emitting Electrochemical Cells

A series of monoanionic Ir(III) complexes (2-4) of general formula [Ir(C^N)2(b-trz)](TBA) are presented, where C^N indicates three different cyclometallating ligands (Hppy = 2-phenylpyridine; Hdfppy = 2-(2,4-difluoro-phenyl)pyridine; Hpqu = 2-methyl-3-phenylquinoxaline), b-trz is a bis-tetrazolate anionic N^N chelator (H2b-trz = di(1H-tetrazol-5-yl)methane), and TBA = tetrabutylammonium. 2-4 are prepared in good yields by means of the reaction of the suitable b-trz bidentate ligand with the desired iridium(III) precursor. The chelating nature of the ancillary ligand, thanks to an optimized structure and geometry, improves the stability of the complexes, which have been fully characterized by NMR spectroscopy and high-resolution MS, while X-ray structure determination confirmed the binding mode of the b-trz ligand. Density functional theory calculations show that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are mainly localized on the metal center and the cyclometalating ligands, while the bis-tetrazolate unit does not contribute to the frontier orbitals. By comparison with selected classes of previously published cationic and anionic complexes with high ligand field and even identical cyclometallating moieties, it is shown that the HOMO-LUMO gap is similar, but the absolute energy of the frontier orbitals is remarkably higher for anionic vs cationic compounds, due to electrostatic effects. 2-4 exhibit reversible oxidation and reduction processes, which make them interesting candidates as active materials for light emitting electrochemical cells, along with red, green, and blue emission, thanks to the design of the C^N ligands. Photoluminescence quantum yields range from 28% (4, C^N = pqu, red emitter) to 83% (3, C^N = dfppy, blue emitter) in acetonitrile, with the latter compound reaching 95% in poly(methyl methacrylate) (PMMA) matrix. In thin films, the photoluminescence quantum yield decreases substantially probably due to the small intersite distance between the complexes and the presence of quenching sites. In spite of this, surprisingly stable electroluminescence was observed for devices employing complex 2, demonstrating the robustness of the anionic compounds.

Carbazole-terpyridine donor–acceptor luminophores

With the aim to combine two versatile molecular units that are widely utilized in materials and coordination chemistry, bischromophoric electron donor–acceptor carbazole–terpyridine systems (Cbz–Tpy) have been synthesized and characterized. The connecting bridge between the two moieties is constituted by phenylene (1), methylene phenylene (2) and ethynylene phenylene (3), which allow tuning of the intercomponent electronic interactions. Electrochemical studies evidence that oxidation and reduction processes occur on the Cbz and Tpy units, respectively, suggesting the possibility of internal charge transfer states located at about 3.10 eV, which is confirmed by photophysical investigations. The absorption spectra of 1 and 3 show a tail above 300 nm, indicating that these conjugated systems exhibit low-energy transitions with charge-transfer character, as confirmed by theoretical studies. At 298 K, 1–3 show a complex pattern of fluorescence profiles as a function of solvent (toluene, dichloromethane, acetonitrile), often with double emissions attributed to transitions localized on individual chromophores or associated to internal charge-transfer processes. The variability of the spectral position affords multiple colours, including white (e.g.3 in acetonitrile). Definitive rationalization and assignment of transitions of 1–3 is obtained through singlet and triplet luminescence spectra at 77 K and by means of DFT and TD-DFT methods using the hybrid functional PBE0 and the long range corrected functional CAM-B3LYP with the polarizable continuum model. This work opens the route to versatile materials based on the Tpy–Cbz motif exhibiting luminescence all across the visible spectral region that can be controlled through electronic conjugation, solvent polarity, temperature, functionalization and cation binding.

Hydroperoxyl Radicals (HOO.): Vitamin E Regeneration and H-Bond Effects on the Hydrogen Atom Transfer

Hydroperoxyl (HOO. ) and alkylperoxyl (ROO. ) radicals show a different behavior in H-atom-transfer processes. Both radicals react with an analogue of α-tocopherol (TOH), but HOO. , unlike ROO. , is able to regenerate TOH by a fast H-atom transfer: TO. +HOO. →TOH+O2 . The kinetic solvent effect on the H-atom transfer from TOH to HOO. is much stronger than that observed for ROO. because noncovalent interactions with polar solvents (Solv⋅⋅⋅HOO. ) destabilize the transition state.