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Dipartimento di Scienze Chimiche e Geologiche - Sede Dipartimento di Scienze Chimiche e Geologiche

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Ghelfi, Franco; L., Cotarca; Roncaglia, Fabrizio; R., Giovannetti; A., Nicoli

A process for preparing gabapentin of formula 1, which comprises Formula (I) converting 1-allyl-cyclohexanecarboxaldehyde into 1-allyl-cyclohexanecarbonitrile; ozonizing 1-allyl-cyclohexanecarbonitrile to obtain 1-cyano-cyclohexaneacetaldehyde; acetalizing 1-cyano-cyclohexaneacetaldehyde with a suitable acetalizing agent to give the corresponding acetal and converting the latter into gabapentin.

2024 - A Continuous Extraction Protocol for the Characterisation of a Sustainably Produced Natural Indigo Pigment [Articolo su rivista]
Frignani, Elia; D’Eusanio, Veronica; Grandi, Mauro; Pigani, Laura; Roncaglia, Fabrizio

2023 - An Efficient Transition-metal-free Route to Oligo-α-pyridylamines via Fluoroarenes [Articolo su rivista]
Nicolini, A.; Anderlini, B.; Roncaglia, F.; Cornia, A.

The new polynucleating tripodal proligand H6tren(dpa)3, containing thirteen nitrogen donors of four different types, was designed, synthesized, and isolated in good yield (~60%) via a transition-metal-free triple N-arylation of H6tren with HXdpa (X = Br or F), using K2CO3 or Cs2CO3 as a base (H6tren = tris(2-aminoethyl)amine, HXdpa = 6-halogeno-N-(pyridin-2-yl)pyridin-2-amine). HFdpa was prepared with excellent yield (90−92%) by reaction of 2,6-difluoropyridine with 2-aminopyridine in LiH/toluene/py and was found more reactive than HBrdpa, affording higher conversion and higher yield. Use of Cs2CO3 turned out to be essential for achieving high regioselectivity and eliminating overarylation almost completely.

2023 - Exploring the potential of peach (Prunus Persica L.) nut-shells as a sustainable alternative to traditional aggregates in lightweight concrete [Articolo su rivista]
D'Eusanio, Veronica; Anderlini, Biagio; Marchetti, Andres; Pastorelli, Stefano; Roncaglia, Fabrizio; Ughetti, Alberto

This study investigates the potential application of peach shells as lightweight aggregates in the production of non-structural lightweight concrete (LWC). The recycling and reutilization of agri-food waste presents an opportunity to address the challenges associated with waste disposal and limit the exploitation of natural resources, contributing to sustainable development goals and combatting climate change. The peach shells were subjected to heat treatment at various temperatures (160, 200, and 240 °C) to reduce the hydrophilicity of the cellulose fraction, and their chemical and physical properties were examined in relation to the performance of lightweight concrete, in terms of density, compressive strength and thermal conductivity. Two binding mixtures, one with lime only (mixture “a”) and the other with both lime and cement (mixture “b”), were studied. The experimental results indicated that the prepared lightweight concrete specimens exhibited better performance as the roasting temperature increased, starting from 200 °C. Conversely, specimens prepared with peach shells roasted at 160 °C exhibited a decreased performance compared to those prepared with only air-dried peach shells. Samples prepared with the mixture “a” have better insulating properties and lower density, but lower mechanical resistance. The enhanced properties observed in the lightweight concrete specimens prepared with higher roasting temperatures highlight the potential of utilizing peach shells as an effective and sustainable alternative to traditional lightweight aggregates.

2023 - Graphite-epoxy composites for bipolar plates: The gas permeability issue [Articolo su rivista]
Roncaglia, Fabrizio; Mucci, Adele; Romagnoli, Marcello; Spinelli, Luca; DI BONA, Alessandro; Biagi, Roberto

To sustain Hydrogen Economy, proton exchange membrane (PEM) devices are expected to play a central role in both the generation of clean hydrogen and its efficient employment. Bipolar plates are an essential part of PEM devices, therefore investigations directed to technical improvement and cost reduction of these components deserve considerable attention. This work represents an extension of our previous study on graphite-epoxy composites suitable for manufacturing bipolar plates and based on the use of cheap and commercially available materials. Through appropriate changes in the formulation of the composites and in the processing conditions, we succeeded in obtaining materials with full technical compliance, in terms of electrical conductivity and gas permeability. The processability and productivity of the method were improved as well, through the reduction of molding times. The variation of the properties of the samples with the molding pressure was analyzed.

2023 - Integrated Carbonate-Based CO2 Capture—Biofixation through Cyanobacteria [Articolo su rivista]
Ughetti, A.; Roncaglia, F.; Anderlini, B.; D’Eusanio, V.; Russo, A. L.; Forti, L.

2023 - Volatile Aroma Compounds of Gavina® Watermelon (Citrullus Lanatus L.) Dietary Fibers to Increase Food Sustainability [Articolo su rivista]
D'Eusanio, Veronica; Maletti, Laura; Marchetti, Andrea; Roncaglia, Fabrizio; Tassi, Lorenzo

2023 - Waste By-Product of Grape Seed Oil Production: Chemical Characterization for Use as a Food and Feed Supplement [Articolo su rivista]
D'Eusanio, Veronica; Malferrari, Daniele; Marchetti, Andrea; Roncaglia, Fabrizio; Tassi, Lorenzo

2022 - Graphite/epoxy composite for building Bipolar Plates [Articolo su rivista]
Spinelli, Luca; Roncaglia, Fabrizio; Biagi, Roberto; di Bona, Alessandro; Romagnoli, Marcello; Mucci, Adele

2022 - Upgrading of Biobased Glycerol to Glycerol Carbonate as a Tool to Reduce the CO2 Emissions of the Biodiesel Fuel Life Cycle [Articolo su rivista]
Anderlini, Biagio; Ughetti, Alberto; Cristoni, Emma; Forti, Luca; Rigamonti, Luca; Roncaglia, Fabrizio

With regards to oil-based diesel fuel, the adoption of bio-derived diesel fuel was estimated to reduce CO2 emissions by approximately 75%, considering the whole life cycle. In this paper, we present a novel continuous-flow process able to transfer an equimolar amount of CO2 (through urea) to glycerol, producing glycerol carbonate. This represents a convenient tool, able to both improve the efficiency of the biodiesel production through the conversion of waste streams into added-value chemicals and to beneficially contribute to the whole carbon cycle. By means of a Design of Experiments approach, the influence of key operating variables on the product yield was studied and statistically modeled.

2021 - An expedient catalytic process to obtain solketal from biobased glycerol [Articolo su rivista]
Roncaglia, F.; Forti, L.; D'Anna, S.; Maletti, L.

Developing simple and effective chemistry able to convert industrial waste streams into valuable chemicals is a primary contributor to sustainable development. Working in the context of biodiesel production, we found that plain bisulfate on silica (SSANa, 3.0 mmol/g) proved to be an optimal catalyst to convert glycerol into solketal. With the assistance of a proper anhydrification technique, isolated yields of 96% were achieved working in mild conditions, on 100 g scale.

2021 - Analytical Concentrations of Some Elements in Seeds and Crude Extracts from Aesculus hippocastanum, by ICP-OES Technique [Articolo su rivista]
Durante, C.; Cocchi, M.; Lancellotti, L.; Maletti, L.; Marchetti, A.; Sighinolfi, S.; Tassi, L.; Roncaglia, F.

The metal content in some samples of horse chestnut seeds (Aesculus hippocastanum) was monitored over time (years 2016, 2017, 2018, 2019) considering the two most common and representative Mediterranean varieties: the pure species (AHP, which gives white flowers) and a hybrid one (AHH, which gives pink flowers). The selected elemental composition of the samples was determined by applying the ICP-OES technique. Several samples obtained from different preliminary treatments of the peeled seeds were examined, such as: i) floury samples (wild type) mineralized with the wet method; ii) the ashes of both AHP and AHH varieties; iii) the fraction of total inorganic soluble salts (TISS). Furthermore, the hydroalcoholic crude extracts (as a tincture) were obtained according to the official Pharmacopoeia methods, and the relevant results were compared with those of a commercial sample, an herbal product - food supplement of similar characteristics. The main characteristics of this research work underline that the two botanical varieties give different distinctive characters, due to the Fe content (80.05 vs 1.42 mg / 100 g d.s., for AHP and AHH - wild type flour samples, respectively), along with K, Ca, Mn, Ni and Cu, which are more abundant in the AHP samples. Furthermore, the PCA analysis was applied to the experimental dataset in order to classify and discriminate the samples, in relation to their similar botanical origin, but different for the color of the bloom. These results can be useful for the traceability of raw materials potentially intended for the production of auxiliary systems of pharmacological interest.

2021 - Development of Graphite-Epoxy Composites for Bipolar Plates in PEM Fuel Cells [Abstract in Atti di Convegno]
Roncaglia, Fabrizio; Spinelli, Luca; Imperato, Manuel; Biagi, Roberto; Romagnoli, Marcello; di Bona, Alessandro; Mucci, Adele

Graphite-Epoxy composites can be a good alternative to metals and metal alloys to build Bipolar Plates (BPs),1 that are important components of Proton Exchange Membrane Fuel Cells (PEMFC), mainly used in hydrogen-powered electric vehicles. We are currently working2 on the preparation of graphite-epoxy composites, suitable for manufacturing BPs meeting the technical targets for 2025.3 Among the overall properties expected for BPs, we are mainly focussing on conductivity, flexural strength and permeability and we are tuning the preparation steps, i.e. composite formulation, mixing and molding, trying to optimize these properties. We compared different resin to filler ratios, dry and wet mixing, mechanical and magnetic stirring and different temperature and pressure ranges. A two-level full factorial Design Of Experiment (DOE) approach was performed to analyze the molding parameters. We observed substantial changes in the properties of the composites, depending on the type of graphite, the mixing method, the epoxy resin to filler ratio and the molding pressure, temperature and time. The results of these studies will be presented.

2021 - Graphite-epoxy composites for fuel-cell bipolar plates: Wet vs dry mixing and role of the design of experiment in the optimization of molding parameters [Articolo su rivista]
Roncaglia, Fabrizio; Romagnoli, Marcello; Incudini, Simone; Santini, Elena; Imperato, Manuel; Spinelli, Luca; di Bona, Alessandro; Biagi, Roberto; Mucci, Adele

Bipolar plates (BPs) are key components of Proton Exchange Membrane Fuel Cells mainly employed in hydrogen-powered electric vehicles. Here, a reliable and detailed experimental method to prepare graphite-epoxy composites suitable for manufacturing BPs is reported. Dry and wet mixing procedures were compared and a simple composition was optimized, with regard to electrical conductivity. The adoption of wet mixing of the components and the choice of the conductive filler were the main factors that contributed to the achievement of good electrical and mechanical properties. The addition of a small percentage of carbon black as a secondary filler was also advantageous. The effects of molding parameters (pressure, temperature, and time) on a graphite-epoxy composite of fixed-composition were modeled using a Design Of Experiments approach, which provided valuable information for future improvements. Conductivity values well above the US DOE requirements were obtained

2021 - Graphite/epoxy composite for building Bipolar Plates [Abstract in Atti di Convegno]
Spinelli, L.; Roncaglia, F.; Biagi, R.; di Bona, A.; Romagnoli, M.; Mucci, A.

2021 - When the metal makes the difference: template syntheses of tridentate and tetradentate salen-type schiff base ligands and related complexes [Articolo su rivista]
Mazzoni, R.; Roncaglia, F.; Rigamonti, L.

The reaction of organic molecules mediated by a metal center (template synthesis) can result in a final connectivity that may differ from the one obtained in the absence of the metal. The condensation of carbonyl fragments with primary amines form C=N iminic bonds, the so-called Schiff bases, which can act as ligands for the templating metal center by means of the lone pair on the nitrogen atom. This review focuses on the template methods for the reaction between a carbonyl compound (mainly salicylaldehyde) and a primary aliphatic diamine able to prevent the double condensation on both amine groups and obtain tridentate N2O ligands. These adducts, still having one free amino group, can further react, yielding tetradentate salen-type Schiff base ligands. A screening over the transition metals able to show such a template effect will be presented, with particular attention to copper(II), together with their peculiar reactivity and the available crystal structure of the metal complexes and related coordination geometries.

2020 - Red horse-chestnut of Aesculus X Carnea : a new way for health and food design? [Capitolo/Saggio]
Baraldi, Cecilia; Foca, Giorgia; Maletti, Laura; Marchetti, Andrea; Roncaglia, Fabrizio; Sighinolfi, Simona; Tassi, Lorenzo

Some investigations have been performed about the composition of Aesculus X carnea seeds (Red horse-chestnuts). Different experimental techniques have been used to gain more information on morphological structure and proximate chemical composition of this product. Surface analysis by SEM showed internal typical structure of globular-form bodies, containing starch, lipids, proteins, mineral components and many others species, confined in cell walls and cemented by a gelled hydrocolloid. The most representative data related to the chemical composition of naturally desiccated specimen are as follows: proteins 3.16%; lipids 4.34%; total glucides 15.6%. Obviously, this chemical faces modulate some other undifferentiated chemical parameters, such as Cold Water Solubility (CWS = 53.9%), and Total Inorganic Soluble Salts (TISS = 2.79%). A stringent comparison of the present findings has been made with our previous results obtained by working with the seeds of two Hippocastanaceae parent cultivars.

Roncaglia, Fabrizio; DI BONA, Alessandro; Imperato, Manuel; Biagi, Roberto; Romagnoli, Marcello; Mucci, Adele

Foca, Giorgia; Leoni, Diego; Lusvardi, Gigliola; Marchetti, Andrea; Roncaglia, Fabrizio; Tassi, Lorenzo

L’invenzione è relativa ad un processo di preparazione di nuovi materiali copolimerici a base di proteine di origine animale e di origine vegetale, indurite mediante agenti reticolanti a struttura furanica recanti gruppi funzionali carbonilici. Il processo produttivo dei biopolimeri consiste nella preparazione di una soluzione / sospensione delle proteine in ambiente acquoso per ottenere la massima distensione delle micelle, eventualmente miscelate con coloranti o pigmenti finemente dispersi, cui si aggiunge infine un agente cross-linkante di tipo furanico solubilizzato o sospeso in un solvente non acquoso e sotto vigorosa agitazione. I prodotti copolimerici termoindurenti ottenibili presentano caratteristiche meccaniche e prestazionali analoghe a quelle della galalite, e sono privi di qualunque rilascio di VOC.

Roncaglia, F.; Di Bona, A.; Biagi, R.; Romagnoli, M.; Degrandis, D.; Mucci, A.

In order to obtain a material suitable for manufacturing bipolar plates for PEM Fuel Cells the effect of molding parameters (pressure, temperature and time), relative to a graphite/epoxy composite of fixed composition, were studied and modeled by means of a two-level full factorial Design Of Experiment approach. In-plane conductivity and mechanical strength were the dependent variables.

2019 - Organic Electrochemical Synthesis of hydrovanilloin, a new bioavailable nontoxic substitute of bisphenol A [Relazione in Atti di Convegno]
Lancellotti, Lidia; Maletti, Laura; Borsari, Marco; Roncaglia, Fabrizio; Tassi, Lorenzo

2018 - Filling the Gap in Extended Metal Atom Chains: Ferromagnetic Interactions in a Tetrairon(II) String Supported by Oligo-α-pyridylamido Ligands [Articolo su rivista]
Nicolini, Alessio; Galavotti, Rita; Barra, Anne-Laure; Borsari, Marco; Caleffi, Matteo; Luo, Guangpu; Novitchi, Ghenadie; Park, Kyungwha; Ranieri, Antonio; Rigamonti, Luca; Roncaglia, Fabrizio; Train, Cyrille; Cornia, Andrea

The stringlike complex [Fe4(tpda)3Cl2] (2; H2tpda = N2,N6-bis(pyridin-2-yl)pyridine-2,6-diamine) was obtained as the first homometallic extended metal atom chain based on iron(II) and oligo-α-pyridylamido ligands. The synthesis was performed under strictly anaerobic and anhydrous conditions using dimesityliron, [Fe2(Mes)4] (1; HMes = mesitylene), as both an iron source and a deprotonating agent for H2tpda. The four lined-up iron(II) ions in the structure of 2 (Fe⋯Fe = 2.94-2.99 Å, Fe⋯Fe⋯Fe = 171.7-168.8°) are wrapped by three doubly deprotonated twisted ligands, and the chain is capped at its termini by two chloride ions. The spectroscopic and electronic properties of 2 were investigated in dichloromethane by UV-vis-NIR absorption spectroscopy, 1H NMR spectroscopy, and cyclic voltammetry. The electrochemical measurements showed four fully resolved, quasi-reversible one-electron-redox processes, implying that 2 can adopt five oxidation states in a potential window of only 0.8 V. Direct current (dc) magnetic measurements indicate dominant ferromagnetic coupling at room temperature, although the ground state is only weakly magnetic. On the basis of density functional theory and angular overlap model calculations, this magnetic behavior was explained as being due to two pairs of ferromagnetically coupled iron(II) ions (J = -21 cm-1 using JŜi·Ŝj convention) weakly antiferromagnetically coupled with each other. Alternating-current susceptibility data in the presence of a 2 kOe dc field and at frequencies up to 1.5 kHz revealed the onset of slow magnetic relaxation below 2.8 K, with the estimated energy barrier Ueff/kB = 10.1(1.3) K.

2018 - New Silver(I) Coordination Polymer with Fe4 Single-Molecule Magnets as Long Spacer [Articolo su rivista]
Rigamonti, Luca; Vaccari, Manuela; Roncaglia, Fabrizio; Baschieri, Carlo; Forni, Alessandra

In continuation of our work on supramolecular architectures of single-molecule magnets (SMMs) as a promising strategy in developing their magnetic performance, in this paper we report the synthesis and single crystal X-ray structure of the centered triangular tetrairon(III) SMM, [Fe4(PhpPy)2(dpm)6], Fe4 (Hdpm = dipivaloylmethane, H3PhpPy = 2-(hydroxymethyl)- 2-(4-(pyridine-4-yl)phenyl)propane-1,3-diol), and its assembly in the coordination polymer {[Fe4(PhpPy)2(dpm)6Ag](ClO4)}n, Fe4Ag, upon reaction with silver(I) perchlorate. Thanks to the presence of the pyridyl rings on the two tripodal ligands, Fe4 behaves as divergent ditopic linker, and due to the Fe4:AgClO4 1:1 ratio, Fe4Ag probably possesses a linear arrangement in which silver(I) ions are linearly coordinated by two nitrogen atoms, forming 1D chains whose positive charge is balanced by the perchlorate anions. The stabilization of such a polymeric structure can be ascribed to the long distance between the two donor nitrogen atoms (23.4 Å) and their donor power. Fe4Ag shows slow relaxation of the magnetization which follows a thermally activated process with Ueff/kB = 11.17(18) K, t0 = 2.24(17) 107 s in zero field, and Ueff/kB = 14.49(5) K, t0 = 3.88(8) 107 s in 1-kOe applied field, in line with what reported for tetrairon(III) SMMs acting as building blocks in polymeric structures.

2018 - Solution structure of a pentachromium(II) single molecule magnet from DFT calculations, isotopic labelling and multinuclear NMR spectroscopy [Articolo su rivista]
Dirvanauskas, Aivaras; Galavotti, Rita; Lunghi, Alessandro; Nicolini, Alessio; Roncaglia, Fabrizio; Totti, Federico; Cornia, Andrea

The structure of pentachromium(II) extended metal atom chain [Cr5(tpda)4Cl2] (2), which behaves as a single molecule magnet at low temperature, was investigated by Density Functional Theory (DFT) calculations and spectroscopic studies without the constraints of a crystal lattice (H2tpda = N2,N6-bis(pyridin-2-yl)pyridine-2,6-diamine). DFT studies both in the gas phase and including CH2Cl2 solvent effects indicate that an unsymmetric structure (C4 point group), with pairs of formally quadruply-bonded metal ions and one terminal metal center, is slightly more stable (2.9 and 3.9 kcal mol-1) than a symmetric structure (D4 point group). Isotopically-labelled samples (2-d8 and 2-d16) have then been prepared to aid in molecular symmetry determination by combined 1H and 2H NMR studies in dichloromethane solution. The spectra are strongly suggestive of a symmetric (D4) framework, indicating fast shuttling between the two unsymmetric forms over the timescale of NMR experiments. Procedures for a high-yield Pd-free synthesis of H2tpda and for site-selective post-synthetic H/D exchange of aromatic H2tpda hydrogens are also reported.

2017 - Designing and Using a Safer, Greener Azole Oxamide for Chemiluminescence Demonstrations [Articolo su rivista]
Roncaglia, F.

The oxamide of 1H-benzotriazole, identified with the guidance of Green Chemistry Principle no. 4, was successfully employed in chemilumiscence demontrations. Its synthesis is highly convenient, as it can work without sacrificial bases.

2016 - Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions [Articolo su rivista]
Clark, Andrew J; Curran, Dennis P.; Fox, David J.; Ghelfi, Franco; Guy, Collette S.; Hay, Benjamin; James, Natalie; Phillips, Jessica M.; Roncaglia, Fabrizio; Sellars, Philip B.; Wilson, Paul; Zhang, Hanmo

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG∞ rotation varied between <8.0 and 31.0 kcal mol-1). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-α-haloacetamides exhibiting relatively high barriers to rotation round the N-alkenyl bond (ΔG∞ rotation >20 kcal mol-1) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol-1) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature.

2015 - Electrochemical Approach to Copper-Catalyzed Reversed Atom Transfer Radical Cyclization [Articolo su rivista]
Isse, Abdirisak A.; Ghelfi, Franco; Roncaglia, Fabrizio; Gennaro, Armando; Visona, Giulia

Electrochemically mediated atom transfer radical cyclization (eATRC) has been developed as an easy and clean method allowing the synthesis of halogenated cyclic compounds. This method has been successfully applied to the copper-catalyzed atom transfer radical cyclization of some N-allyl-alpha,alpha-dichloroamides in acetonitrile (CH3CN) using a copper complex with tris(2-pyridylmethyl)amine (TPMA) with a metal loading of 1%. The catalyst is introduced as [Cu(II)TPMA](2+) and is activated and continuously regenerated to its active copper(I) form by reduction at a platinum (Pt) electrode. During the ATRC process a new copper(II) complex, namely, [ClCu(II)TPMA](+), whose reduction potential is ca. 0.350 V more negative than that of the starting [Cu(II)TPMA](2+), is formed. Therefore, the choice of the applied potential is critical and should be done taking care that all copper(II) species are reduced to copper(I). The compounds undergo very high conversions (79-100%) in a few hours of electrolysis, producing a cyclic gamma-lactam (yield 60-98%) as a mixture of two isomers, with a good cis-diastereoselectivity [dr (cis/trans) = 59/41-83/17]. [Cu(II)PMDE-TA](2+) (PMDETA= N, N, N',N '',N ''-pentamethyldiethylenetriamine) which is much cheaper, albeit less reactive than [Cu(II)TPMA](2+), was also investigated but the results were not satisfactory.

2014 - Arylsulfonyl Groups: The Best Cyclization Auxiliaries for the Preparation of ATRC γ-Lactams can be Acidolytically Removed [Articolo su rivista]
Clark, A. J.; Cornia, Andrea; Felluga, F.; Gennaro, A.; Ghelfi, Franco; Isse, A. A.; Menziani, Maria Cristina; Muniz Miranda, F.; Roncaglia, Fabrizio; Spinelli, D.

The N-arylsulfonyl group, which is the best and most useful cyclization auxiliary for the transition-metal-catalyzed atom transfer radical cyclization (ATRC) of N-allyl-α-polychloroamides, can be effectively removed from the target γ-lactams by using H2SO4–HOAc, without impairing the halogen functions. The reaction involves H+ attack on the aromatic moiety, and is strongly responsive to the electronic properties of the substituent bound to the aromatic ring: electron-donating groups, such as methyl or methoxy are, in fact, required for efficient “deprotection”. The N-p-nitrophenylsulfonyl cyclization auxiliary, in contrast to all the other sulfonyl groups tested, proved to be unsuitable for the ATRC, owing to a side reductive transposition that halts the redox cycle.

2014 - Simultaneous deprotection-oxidation of cyclic hemiacetals: A fine ending for a Ueno-Stork ATRC to dichloro-γ-lactones [Articolo su rivista]
Roncaglia, Fabrizio; Ghelfi, Franco; Felluga, Fulvia; Poppi, Valentina

Recently we found that a copper catalysed Ueno–Stork cyclization can be a very useful means for the expedient synthesis of dichloro-gamma-lactones, but, to take advantage of this step, the method still lacks of an efficient and selective follow-up. This Letter describes our progress in that field, unveiling the use of a supported and recyclable Cr(VI) catalyst for the simultaneous deprotection and oxidation of cyclic dichloro hemiacetals.

2013 - Efficient and Green Route to γ-Lactams by Copper-Catalysed Reversed Atom Transfer Radical Cyclisation of α-Polychloro-N-allylamides, using a Low Load of Metal (0.5 mol%) [Articolo su rivista]
Bellesia, Franco; Andrew J., Clark; Fulvia, Felluga; Armando, Gennaro; Abdirisak A., Isse; Roncaglia, Fabrizio; Ghelfi, Franco

The cyclisation of N-allyl-N-substituteda- polychloroamides is efficiently obtained through a copper-catalysed activators regenerated by electron transfer–atom transfer radical cyclisation process, with a metal load of only 0.5 mol%. The redox catalyst is introduced in its inactive form as copper( II) chloride/[nitrogen ligand] complex, and continuously regenerated to the active copper(I) chloride/[ nitrogen ligand] species by ascorbic acid. To preserve the catalyst integrity, the hydrochloric acid, released after each regeneration cycle, has been quenched by carbonate. The choice of the solvent is critical, the best performance being observed in ethyl acetate-ethanol (3:1).

2013 - Novel Route to Chaetomellic Acid A and Analogues: Serendipitous Discovery of a more Competent FTase Inhibitor [Articolo su rivista]
Bellesia, Franco; Seoung ryoung, Choi; Fulvia, Felluga; Giuliano, Fiscaletti; Ghelfi, Franco; Menziani, Maria Cristina; Andrew F., Parsons; C., Dale Poulter; Roncaglia, Fabrizio; Massimo, Sabbatini; Domenico, Spinelli

A new practical route to chaetomellic acid A (ACA), based on the copper catalysed radical cyclization (RC) of (Z)-3-(2,2-dichloropropanoyl)-2-pentadecylidene-1,3-thiazinane, is described. Remarkably, the process entailed: (i) a one-pot preparation of the intermediate N-a-perchloroacyl-2-(Z)-alkyliden-1,3-thiazinanes starting from N-(3-hydroxypropyl)palmitamide, (ii) a two step smooth transformation of the RC products into ACA and (iii) only one intermediate chromatographic purification step. The method offers a versatile approach to the preparation of ACA analogues, through the synthesis of an intermediate maleic anhydride with a vinylic group at the end of the aliphatic tail, a function that can be transformed through a thiol–ene coupling. Serendipitously, the disodium salt of 2-(9-(butylthio)nonyl)-3-methylmaleic acid, that we prepared as a representative sulfurated ACA analogue, was a more competent FTase inhibitor than ACA. This behaviour was analysed by a molecular docking study.

2012 - CuCl catalyzed radical cyclisation of N-alpha-perchloroacyl-ketene-N,S-acetals: a new way to prepare disubstituted maleic anhydrides [Articolo su rivista]
Cornia, Andrea; F., Felluga; V., Frenna; Ghelfi, Franco; A. F., Parsons; M., Pattarozzi; Roncaglia, Fabrizio; D., Spinelli

The copper catalyzed radical cyclization (RC) of N-α-perchloroacyl cyclic ketene-N,X(X = O, NR, S)-acetals was studied. While the RC of N-acyl ketene-N,O-acetals was unsuccessful, the 5-endo cyclization provided much better results, with the following order of cyclization efficiency: hexa-atomic cyclic ketene-N,NR-acetals < penta-atomic cyclic ketene-N,S-acetals < hexa-atomic cyclic ketene-N,S-acetals. Invariably the catalytic cycle begins with the formation of a carbamoyl methyl radical. This leads to a cascade of reactions, including a radical polar crossover step, which ends with the formation of the maleimide nucleus, or precursors of this. Products from the RC of the hexa-atomic cyclic ketene-N,S-acetals, were efficiently transformed into disubstituted maleic anhydrides.

2011 - Acetic Anhydride/Et3N/DMAP: An Effective Acetylating System for Hemiacetals [Articolo su rivista]
Roncaglia, Fabrizio; A. F., Parsons; Bellesia, Franco; Ghelfi, Franco

The selective and efficient acetylation of the hemiacetal hydroxyl in the equilibrium mixture between RCl2C(OAll)OH and AllOH/RCl2CHO was achieved using the acylating system Ac2O/Et3N/dimethylaminopyridine (DMAP).

2010 - 'Ligand-free-like' CuCl-catalyzed atom transfer radical cyclization of N-substituted N-allyl polychloroamides to γ-lactams. [Articolo su rivista]
M., Pattarozzi; Roncaglia, Fabrizio; V., Giangiordano; P., Davoli; Prati, Fabio; Ghelfi, Franco

Atom transfer radical cyclization (ATRC) of N-alkyl N-allyl dichloroamides to γ-lactams, catalyzed by 'naked' CuCl, worked efficiently in DMF, whereas, when the same dichloroamides were N-sulfonylated, DMF needed to be replaced by acetonitrile. The outcome of the cycloisomerization with N-substituted N-allyl trichloroacetamides was less affected by solvent choice, although for an effective reaction to occur, the solvent had to dissolve the cuprous salt. Catalyst loading ranged between 5 and 20 mol%.

2010 - Esterase-mediated synthesis of optically active GABA analogues containing a stereogenic all-carbon quaternary carbon atom. [Articolo su rivista]
F., Felluga; Ghelfi, Franco; G., Pitacco; Roncaglia, Fabrizio; E., Valentin; C. D., Venneri

Esterase from Horse Liver (HLAP) was able to hydrolyze a series of linear and cyclic b,b-dialkyl-c-nitroesters, in spite of the well-known reluctance of hydrolytic enzymes to recognize and transform hindered substrates, such as those possessing a stereogenic quaternary carbon atom next to the reaction site. The resulting optically active c-nitroesters gave access to optically active b,b-disubstituted c-aminoacids as well as a,a-disubstituted succinic acids, both being biologically relevant compounds.

2010 - Expedient Synthesis, on Large Scale, of Aliphatic Chaetomellic Anhydrides from N-Allyl-2,2-dichlorocarboxyamides [Articolo su rivista]
Ghelfi, Franco; Pattarozzi, Mariella; Roncaglia, Fabrizio; Giangiordano, Valerio; A. F., Parsons

Chaetomellic anhydride A and an analog (with two addnl. carbons) were obtained, on a preparative scale, starting from amides derived from the acylation of 2-(2-propenylamino)pyridine with 2,2-dichloropalmitic or 2,2-dichlorostearic acid. An alternative approach, in which the Me substituent of the target anhydride is introduced by the carboxylic acid reactant and the long aliph. chain is added through the allylamino moiety, proved unviable.

2010 - Functional rearrangement of 3-Cl or 3,3-diCl-γ-lactams bearing a secondary 1-chloroalkyl substituent at C-4 [Articolo su rivista]
Pattarozzi, Mariella; Roncaglia, Fabrizio; L., Accorsi; A. F., Parsons; Ghelfi, Franco

The study of the reaction with MeONa/MeOH of chlorinated , prepd. from the atom transfer radical cyclization of N-allyl-α-perchloroamides, has been extended to the case of substrates carrying an exo halogen atom on a branched carbon. Only with secondary exo C-Cl groups, that are not located on a fused ring, does the functional rearrangement follow the typical transformation route, which with trichloro-lactams can proceed further to give 4-alkylidene derivs. From a practical point of view, the outcome of the reaction with di- or trichloro N-cinnamylamides is synthetically valuable, affording the 5-methoxy-1H-pyrrol-2(5H)-one or 3-benzylidenepyrrolidine-2,5-dione, resp., in good to excellent yield.

2010 - Ligand-free-like cucl-catalyzed atom transfer radical cyclization of N-substituted N -allyl polychloroamides to -γlactams (Synthesis (2010) (694)) [Articolo su rivista]
Pattarozzi, M.; Roncaglia, F.; Giangiordano, V.; Davoli, P.; Prati, F.; Ghelfi, F.

2009 - A new synthetic route to Tyromycin A and its analogue from renewable resources [Articolo su rivista]
Roncaglia, Fabrizio; C. V., Stevens; Ghelfi, Franco; M., Van der Steen; Pattarozzi, Mariella; L., De Buyck

The synthesis of tyromycin A and that of the non-natural lower homologue, involving as featuring stepsa transition metal catalyzed atom transfer radical cyclization and a functional rearrangement of thepolyhalogenated 2-pyrrolidinones thus obtained, are described. Both routes use 10-undecenoic acid,a renewable source from castor oil, as starting material for the preparation of the pivotal intermediatesa,a,a0,a0-tetrachlorodicarboxylic acids.

2009 - Atom transfer radical cyclization of O-allyl-2,2-dichlorohemiacetal acetates: an expedient method to dichloro-gamma-lactones. [Articolo su rivista]
Ghelfi, Franco; Roncaglia, Fabrizio; Pattarozzi, Mariella; Giangiordano, Valerio; G., Petrillo; F., Sancassan; A. F., Parsons

3-Alkyl-3-chloro-4-chloromethyl--lactones were synthesized in acceptable yields, exploiting the CuCl-N,N,N’,N”,N”-pentamethyldiethylenetriamine catalyzed atom transfer radical cyclization (ATRC) of O-allyl-2,2-dichlorohemiacetal acetates, starting materials easily prepared from 2,2-dichloroaldehydes. The oxidation of the intermediate dichloro-2-acetoxytetrahydrofurans was completed in a two step, one-pot procedure: hydrolysis to gamma-lactol and final oxidation to lactone with the Jones’ reagent.

2009 - Synthesis of the disubstituted maleic anhydride frame using a novel tandem radical-polar reaction [Articolo su rivista]
Pattarozzi, Mariella; Ghelfi, Franco; Roncaglia, Fabrizio; Pagnoni, Ugo Maria; A. F., Parsons

An unreported 5-endo-trig atom transfer radical cyclization of cyclic N--dichloroacyl-ketene-N,S-acetals, which evolves as a tandem radical-polar process, is described. The reaction, which is carried out in the presence of a Cu(I) complex catalyst (10 mol%) and an inorganic base (i.e. carbonate), can be exploited as the key step for a novel, short and versatile synthesis of the 3,4-disubstituted maleic anhydride nucleus.

2008 - Preparation of the Maleic Anhydride Nucleus from Dichloro γ-Lactams: Focus on the Role of the N-Substituent in the Functional Rearrangement and in the Hydrolytic Steps [Articolo su rivista]
Ghelfi, Franco; M., Pattarozzi; Roncaglia, Fabrizio; A. F., Parsons; F., Felluga; Pagnoni, Ugo Maria; E., Valentin; Mucci, Adele; Bellesia, Franco

The preparation of the 3,4-dialkyl-substituted maleic anhydride nucleus, through the functional rearrangement of dichloro γ-lactams, allowed the comparison of various N-substituents in the functional rearrangement step. The 2-pyridyl group proved to be the most appropriate N-substituent for the hydrolysis of the 5-methoxy-1,5-dihydro-2H-pyrrol-2-one intermediate into the 5-hydroxy adduct, and for the hydrolysis of the maleimide nucleus into the maleic anhydride. The oxidation of the 5-hydroxy-1,5-dihydro-2H-pyrrol-2-one into the corresponding maleimide was achieved with manganese(IV) oxide.

2008 - Radical initiation using borole derivatives [Articolo su rivista]
Montgomery, I.; Parsons, A. F.; Ghelfi, Franco; Roncaglia, Fabrizio

2-Propylbenzo[d][1,3,2]dioxaborole and related derivatives are shown to initiate a range of radical reactions under mild conditions.

2008 - Undecylenic acid: a valuable renewable Building Block on route to Tyromycin A derivatives [Articolo su rivista]
M., Van der Steen; C. V., Stevens; Y., Eeckhout; L., De Buyck; Ghelfi, Franco; Roncaglia, Fabrizio

A key intermediate for the synthesis of Tyromycin A, a C-20 tetrachlorodicarboxylic acid, was produced in six steps starting with a dimerisation of methyl 10-undecenoate which was obtained from a renewable resource, e.g. castor oil. The acyloin condensation product was then oxidised, transformed to the diene, followed by ozonisation, chlorination and finally oxidation to the corresponding tetrachlorodicarboxylic acid.

2007 - A novel short approach to (Z)-pulchellalactam through Transition-Metal-Catalized Atom-Transfer Radical Cyclization of 1-isopropylprop-2-enyl dichloroacetate [Articolo su rivista]
F., Felluga; Ghelfi, Franco; Pagnoni, Ugo Maria; Af, Parsons; M., Pattarozzi; Roncaglia, Fabrizio; E., Valentin

A new five-step route to the CD45 protein tyrosine phosphatase inhibitor (Z)-pulchellalactam is presented. Key steps are the CuCl-bipyridine catalysed atom transfer radical cyclization of an appropriate allyl ,-dichloroacetate and the subsequent dehydrochlorination/prototropic rearrangement of the resulting dichlorolactone.

2007 - Atom Tranfer Radical Cyclization (ATRC) applied to a chemo-enzymatic synthesis of Quercus Lactones [Articolo su rivista]
Felluga, F; Forzato, C; Ghelfi, Franco; Nitti, P; Pitacco, G; Pagnoni, Ugo Maria; Roncaglia, Fabrizio

The natural fragrances (+)-trans whisky lactone 2 and (+)-trans cognac lactone 4, together with a minor amount of their ()-cis stereoisomers, were prepared in 50% and 42% overall yield, respectively, starting from racemic 1-hepten-3-ol (±)-5 and 1-octen-3-ol(±)-6. The procedure involved first the enantioconvergent, lipase mediated transformation of the secondary allylic alcohols deriveddichloroacetates (±)-7 and (±)-8 into the corresponding homochiral (+)-7 and (+)-8, combined with their cyclization under a transitionmetal catalyzed atom transfer process.

2007 - Lipase-catalysed deacetylation of botryodiplodin acetate [Articolo su rivista]
C., Forzato; G., Furlan; Ghelfi, Franco; P., Nitti; G., Pitacco; Roncaglia, Fabrizio; E., Valentin

Enantioselective deacetylation of -(±)-botryodiplodin acetate was successfully accomplished by means of Lipase PS to afford -(+)-botryodiplodin and -(+)-botryodiplodin acetate with high enantiomeric excesses. Enzyme-mediated transesterification of the acetylated molecule with n-butanol as well as its hydrolysis in several organic solvents are also reported. The CD spectra of -(+)-botryodiplodin and -(+)-botryodiplodin acetate are also presented.

2006 - A new and effective route to (+/-)-botryodiplodin and (+/-)-epi-botryodiplodin acetates using a halogen atom transfer Ueno-Stork cyclization [Articolo su rivista]
L., DE BUYCK; C., Forzato; Ghelfi, Franco; Mucci, Adele; P., Nitti; Pagnoni, Ugo Maria; Af, Parsons; G., Pitacco; Roncaglia, Fabrizio

(+/-)-Botryodiplodin and (+/-)-epi-botryodiplodin acetates were prepared in good yields following a practical four step route. The method, for the construction of the strategic tetrahydrofuran ring, hinged on an unprecedented halogen atom transfer Ueno-Stork cyclization of an O-allyl alpha,alpha-dihalohemiacetal acetate, catalyzed by the redox complex CuCl/N,N,N ',N '',N ''-pentamethyldiethylenetriamine. (c) 2006 Elsevier Ltd. All rights reserved.

2006 - A short approach to chaetomellic anhydride A from2,2-dichloropalmitic acid: elucidation of the mechanism governingthe functional rearrangement of the chlorinatedpyrrolidin-2-one intermediate [Articolo su rivista]
Bellesia, Franco; Danieli, Chiara; L., De Buyck; R., Galeazzi; Ghelfi, Franco; Mucci, Adele; M., Orena; Pagnoni, Ugo Maria; A. F., Parsons; Roncaglia, Fabrizio

Chaetomellic anhydride A was efficiently attained in three steps, starting from 2,2-dichloropalmitic acid and 2-(3-chloro-2-propenylamino)pyridine. Atom transfer radical cyclisation selectively formed the cis-stereoisomer of the trichloropyrrolidin-2-one, which underwent a stereospecific functional rearrangement to form a substituted maleimide. The choice of 2-pyridyl, as ‘cyclisation auxiliary’ in the atom transfer radical cyclisation step, proved beneficial for hydrolysis of the maleimide to form the desired anhydride.

2005 - A new route to (±)-erythro-roccellic acid and chaetomellic anhydride C through functional rearrangement, promoted by n-propylamine or CH3ONa/CH3OH, of N-propyl-3-chloro-4-dichloromethyl-3-dodecylpyrrolidin-2-one [Articolo su rivista]
L., De Buyck; Danieli, Chiara; Ghelfi, Franco; Pagnoni, Ugo Maria; Af, Parsons; Pattarozzi, Mariella; Roncaglia, Fabrizio

The rearrangement of a trichloro-pyrrolidin-2-one, prepared by the CuCl-TMEDA catalyzed atom transfer radical cyclization of N-alkyl-N-(3-chloro-2-propenyl)-2,2-dichloromyristamide, with n-propylamine or CH3ONa/CH3OH, is the key step of a new, short and inexpensive route to chaetomellic anhydride C and (+/-)-erythro-roccellic acid.

2005 - Nuova sintesi della (+/-)-Botriodiplodina attraverso ciclizzazione di Ueno-Stork a trasferimento di atomo [Abstract in Atti di Convegno]
Roncaglia, Fabrizio; L., De Buyck; Bellesia, Franco; C., Forzato; Ghelfi, Franco; L., Goldoni; Mucci, Adele; Pagnoni, Ugo Maria; A. F., Parsons; E., Valentin

E' presentata una nuova sintesi della (+/-)-Botriodiplodina attraverso ciclizzazione di Ueno-Stork a trasferimento di atomo

2005 - Sintesi della (+/-)-Botriodiplodina e della sua forma Epi attraverso una ciclizzazione di Ueno-Stork a trasferimento di atomo [Abstract in Atti di Convegno]
Roncaglia, Fabrizio; L., De Buyck; Bellesia, Franco; C., Forzato; Ghelfi, Franco; L., Goldoni; Mucci, Adele; Pagnoni, Ugo Maria; A. F., Parsons; E., Valentin

E' riportata la sintesi della (+/-)-botriodiplodina e della sua forma Epi attraverso una ciclizzazione di Ueno-Stork a trasferimento di atomo

2005 - Studio di una via più versatile per la preparazione di nuclei 2,5-furandionici disostituiti [Abstract in Atti di Convegno]
L., De Buyck; Ghelfi, Franco; Mucci, Adele; Pagnoni, Ugo Maria; A. F., Parsons; Pinetti, Adriano; Roncaglia, Fabrizio

Si riporta lo studio di una via più versatile per la preparazione di nuclei 2,5-furandionici disostituiti

2000 - 2,2-dichlorination of aldehydes with the 2,6-lutidine center dot HCl/Cl-2/CH2Cl2 system: An environmentally benign process suitable for scale up [Articolo su rivista]
Bellesia, Franco; L., De Buyck; Ghelfi, Franco; Libertini, Emanuela; Pagnoni, Ugo Maria; Roncaglia, Fabrizio

An effective and environmentally benign preparation of 2,2-dichloroaldehydes has been achieved by chlorination of aldehydes with Cl-2(g) in CH2Cl2, using 2,6-lutidine hydrochloride as recoverable catalyst. Remarkable qualities of the process are: easy work up, high purity products, HCl as the only 'waste' stream and inherent bias to the scale up. (C) 2000 Elsevier Science Ltd. All rights reserved.