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Francesco FINI

Professore Associato
Dipartimento di Scienze della Vita sede ex Chimica V.Campi 103

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Pubblicazioni

2023 - Sulfonamidoboronic Acids as “Cross-Class” Inhibitors of an Expanded-Spectrum Class C Cephalosporinase, ADC-33, and a Class D Carbapenemase, OXA-24/40: Strategic Compound Design to Combat Resistance in Acinetobacter baumannii [Articolo su rivista]
Introvigne, Maria Luisa; Beardsley, Trevor J.; Fernando, Micah C.; Leonard, David A.; Wallar, Bradley J.; Rudin, Susan D.; Taracila, Magdalena A.; Rather, Philip N.; Colquhoun, Jennifer M.; Song, Shaina; Fini, Francesco; Hujer, Kristine M.; Hujer, Andrea M.; Prati, Fabio; Powers, Rachel A.; Bonomo, Robert A.; Caselli, Emilia
abstract

2022 - Asymmetric Organocatalysis—A Powerful Technology Platform for Academia and Industry: Pregabalin as a Case Study [Articolo su rivista]
Giorgianni, G.; Bernardi, L.; Fini, F.; Pesciaioli, F.; Secci, F.; Carlone, A.
abstract

Enantioselective organocatalysis has quickly established itself as the third pillar of asymmetric catalysis. It is a powerful technology platform, and it has a tremendous impact in both academic and industrial settings. By focusing on pregabalin, as a case study, this Perspective aims to show how a process amenable to industry of a simple chiral molecule can be tackled in several different ways using organocatalysis.

2021 - Asymmetric Organocatalysis Accelerated via Self-Assembled Minimal Structures [Articolo su rivista]
Sinibaldi, A.; Della Penna, F.; Ponzetti, M.; Fini, F.; Marchesan, S.; Baschieri, A.; Pesciaioli, F.; Carlone, A.
abstract

Self-assembling minimalistic peptides embedded with an organocatalytic moiety were designed. By controlling the formation of fibrils via external intervention, it was shown that the activation is accelerated when the organocatalyst is in its supramolecular state. The effect of the accelerated catalysis was demonstrated in a Michael benchmark reaction.

2021 - Industrial Relevance of Asymmetric Organocatalysis in the Preparation of Chiral Amine Derivatives in Methodologies in Amine Synthesis (Eds.: A. Ricci, L. Bernardi) [Capitolo/Saggio]
Bernardi, Luca; Carlone, Armando; Fini, Francesco
abstract

This chapter covers the emerging utilization of organocatalytic methodologies in industrial settings directed at the large-scale preparation of enantioenriched amines and N-heterocycles. First, some selected manufacturing processes, based on organocatalytic stereodetermining steps, are commented concisely. Despite the generally high catalyst loadings required, these examples show that the relatively low cost of organic catalysts makes the development of cost-effective industrial routes possible. Then, three case studies (pregabalin, the bicyclic core of telaprevir, and 5-(trifluoromethyl)-2-isoxazolines) are discussed. These chiral targets have been approached through a variety of enantioselective strategies, among which the organocatalytic ones stand out for their versatility and potential for scale-up. Recent applications of organocatalysis in industrial settings are not restricted to a single activation mode or a class of catalysts. They encompass the whole catalyst and reaction repertoire typical of this relatively novel catalytic approach to asymmetric synthesis. Asymmetric organocatalysis proves to be, therefore, a useful and versatile synthetic tool for the industrial preparation of chiral compounds.

2021 - Insights in the rheological properties of PLGA-PEG-PLGA aqueous dispersions: Structural properties and temperature-dependent behaviour [Articolo su rivista]
Cespi, M.; Bonacucina, G.; Tiboni, M.; Casettari, L.; Cambriani, A.; Fini, F.; Perinelli, D. R.; Palmieri, G. F.
abstract

PLGA-PEG-PLGA are copolymers, able to form temperature-dependent hydrogels or sol dispersions at selective conditions. A general overview about the rheological characterization of their aqueous dispersions, focusing how the structural characteristics (e.g. molecular weight, PEG/PLGA ratio) affect their temperature-dependent behaviour, is presented. Different PLGA-PEG-PLGA were synthesized by varying the amount of lactide and glycolide and the amount and molecular weight of PEG. All polymers were characterized by gel-permeation chromatography and differential scanning calorimetry. Then, polymeric dispersions in water (15%–25% w/w) were analysed by oscillatory rheological measurements. At solid state, all copolymers are amorphous and the calculated glass transition temperatures were dependent on PEG/PLGA ratio. As regard aqueous dispersions, the temperature-dependent rheological behaviour named “partially thermogelling” has been described, in addition to the commonly reported thermogelling one. In these samples, the consistency increases over temperature without forming a three-dimensional network as for real hydrogels. All rheological characteristics can be explained according to the proposed categorization (thermogel, partial thermogel and sol dispersion).

2021 - Straightforward synthesis of chiral non-racemic α-boryl isocyanides [Articolo su rivista]
Fini, Francesco; Zanni, Alessandro; Introvigne, Maria Luisa; Stucchi, Mattia; Caselli, Emilia; Prati, Fabio
abstract

A straightforward concise synthesis of chiral non-racemic aliphatic alpha-boryl isocyanides, relay intermediates for boron-based bioactive molecules in multicomponent reactions, is presented. The short synthetic sequence comprises as key steps copper-catalysed asymmetric borylation of imines, simultaneous nitrogen formylation/boron-protecting group interconversion and the final formamide dehydration reaction.

2020 - 1,2,3-Triazolylmethaneboronate: A Structure Activity Relationship Study of a Class of β-Lactamase Inhibitors against Acinetobacter baumannii Cephalosporinase [Articolo su rivista]
Caselli, E.; Fini, F.; Introvigne, M. L.; Stucchi, M.; Taracila, M. A.; Fish, E. R.; Smolen, K. A.; Rather, P. N.; Powers, R. A.; Wallar, B. J.; Bonomo, R. A.; Prati, F.
abstract

Boronic acid transition state inhibitors (BATSIs) are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific BATSIs bearing an amide side chain mimicking the β-lactam's amide side chain are an established and recognized synthetic strategy. Herein, we describe a new class of BATSIs where the amide group is replaced by a bioisostere triazole; these compounds were designed as molecular probes. To this end, a library of 26 α-triazolylmethaneboronic acids was synthesized and tested against the clinically concerning Acinetobacter-derived cephalosporinase, ADC-7. In steady state analyses, these compounds demonstrated Ki values ranging from 90 nM to 38 μM (±10%). Five compounds were crystallized in complex with ADC-7 β-lactamase, and all the crystal structures reveal the triazole is in the putative amide binding site, thus confirming the triazole-amide bioisosterism. The easy synthetic access of these new inhibitors as prototype scaffolds allows the insertion of a wide range of chemical groups able to explore the enzyme binding site and provides insights on the importance of specific residues in recognition and catalysis. The best inhibitor identified, compound 6q (Ki 90 nM), places a tolyl group near Arg340, making favorable cation-π interactions. Notably, the structure of 6q does not resemble the natural substrate of the β-lactamase yet displays a pronounced inhibition activity, in addition to lowering the minimum inhibitory concentration (MIC) of ceftazidime against three bacterial strains expressing class C β-lactamases. In summary, these observations validate the α-triazolylboronic acids as a promising template for further inhibitor design.

2020 - The β-Lactamase Inhibitor Boronic Acid Derivative SM23 as a New Anti-Pseudomonas aeruginosa Biofilm [Articolo su rivista]
Peppoloni, S.; Pericolini, E.; Colombari, B.; Pinetti, D.; Cermelli, C.; Fini, F.; Prati, F.; Caselli, E.; Blasi, Elisabetta
abstract

Pseudomonas aeruginosa is a Gram-negative nosocomial pathogen, often causative agent of severe device-related infections, given its great capacity to form biofilm. P. aeruginosa finely regulates the expression of numerous virulence factors, including biofilm production, by Quorum Sensing (QS), a cell-to-cell communication mechanism used by many bacteria. Selective inhibition of QS-controlled pathogenicity without affecting bacterial growth may represent a novel promising strategy to overcome the well-known and widespread drug resistance of P. aeruginosa. In this study, we investigated the effects of SM23, a boronic acid derivate specifically designed as β-lactamase inhibitor, on biofilm formation and virulence factors production by P. aeruginosa. Our results indicated that SM23: (1) inhibited biofilm development and production of several virulence factors, such as pyoverdine, elastase, and pyocyanin, without affecting bacterial growth; (2) decreased the levels of 3-oxo-C12-HSL and C4-HSL, two QS-related autoinducer molecules, in line with a dampened lasR/lasI system; (3) failed to bind to bacterial cells that had been preincubated with P. aeruginosa-conditioned medium; and (4) reduced both biofilm formation and pyoverdine production by P. aeruginosa onto endotracheal tubes, as assessed by a new in vitro model closely mimicking clinical settings. Taken together, our results indicate that, besides inhibiting β-lactamase, SM23 can also act as powerful inhibitor of P. aeruginosa biofilm, suggesting that it may have a potential application in the prevention and treatment of biofilm-associated P. aeruginosa infections.

2020 - The β-lactamase Inhibitor Boronic Acid SM23 Inhibits Pseudomonas aeruginosa Biofilm Formation and Virulence Factor Production [Poster]
Peppoloni, Samuele; Pericolini, Eva; Colombari, Bruna; Pinetti, Diego; Cermelli, Claudio; Fini, Francesco; Prati, Fabio; Caselli, Emilia; Blasi, Elisabetta
abstract

Introduction: Pseudomonas aeruginosa is a Gram-negative nosocomial pathogen, often responsible of severe device-related infections, given its great ability to produce biofilm. P. aeruginosa finely regulates the expression of different virulence factors, including biofilm production, by Quorum Sensing (QS), an intercellular communication mechanism used by many bacteria. Biofilm formation enhances bacterial resistance to antimicrobial agents due to a decreased penetration of antibiotics and a reduced rate of growth of embedded bacteria. Thus, novel agents capable of selective inhibiting biofilm formation may represent a promising strategy to overcome the well-known and widespread drug-resistance of P. aeruginosa. Material and Methods: by using the bioluminescent P. aeruginosa strain P1242, we investigated the effects of SM23, a boronic acid derivative specifically designed as beta-lactamase inhibitor, on biofilm formation and virulence factor production by P. aeruginosa. Results: we found that SM23: a) inhibited both biofilm formation and production of the virulence factors, pyoverdine, elastase and pyocyanin, without affecting bacterial growth; b) decreased the levels of QS-related autoinducers molecules, namely 3-oxo-C12-HSL and C4-HSL, by reducing lasR/lasI system gene expression in the biofilm; c) failed to bind to bacterial cells that had been preincubated with P. aeruginosa-conditioned medium; d) reduced significantly P. aeruginosa biofilm and pyoverdine production on endotracheal tubes, an in vitro condition closely mimicking clinical settings. Discussion and Conclusions: taken together, our results indicate that, besides inhibiting beta-lactamase, the boronic acid SM23, can also act as potent inhibitor of P. aeruginosa virulence, by profoundly affecting biofilm and QS-related signals. These findings highlight potential application of this compound in the prevention and treatment of biofilm-associated P. aeruginosa infections.

2020 - The β-lactamase Inhibitor Boronic Acid SM23 as a new anti-Pseudomonas aeruginosa Biofilm Compound [Poster]
Peppoloni, Samuele; Pericolini, Eva; Colombari, Bruna; Pinetti, Diego; Cermelli, Claudio; Fini, Francesco; Prati, Fabio; Blasi, Elisabetta; Caselli, Emilia
abstract

BACKGROUND: Pseudomonas aeruginosa is a Gram-negative nosocomial pathogen, often causative agent of severe device-related infections, given its great ability to produce biofilm. P. aeruginosa finely regulates the expression of numerous virulence factors, including biofilm production, by Quorum Sensing (QS), an intercellular communication mechanism used by many bacteria. Biofilm formation can enhance bacterial resistance to antimicrobial agents due to a decreased penetration of the antibiotic and a reduced rate of bacterial cells in biofilm. Selective inhibition of biofilm formation may thus represent a novel promising strategy to overcome the well-known and widespread drug-resistance of P. aeruginosa. METHODS: In this study, we investigated the effects of SM23, a boronic acid derivate specifically designed as β-lactamase inhibitor, on biofilm formation and production of virulence factors, using the P. aeruginosa bioluminescent strain P1242. RESULTS: Our results indicated that SM23: a) inhibited the development of biofilm and the production of the virulence factors pyoverdine, elastase and pyocyanin, without affecting bacterial growth; b) decreased the levels of P. aeruginosa QS-related Autoinducers molecules 3-oxo-C12-HSL and C4-HSL by dampened lasR/lasI system gene expression in the biofilm; c) failed to bind to bacterial cells that had been preincubated with P. aeruginosa-conditioned medium; d) reduced both biofilm formation and pyoverdine production by P. aeruginosa onto endotracheal tubes, as assessed by a new in vitro model, closely mimicking the clinical settings. CONCLUSION: Taken together, our results indicate that, besides inhibiting β-lactamase, SM23 can also act as potent inhibitor of P. aeruginosa biofilm, suggesting that it may have a potential application in the prevention and treatment of biofilm-associated P. aeruginosa infections.

2019 - A Regio- and Stereoselective Carbonylative Approach to Alkyl (Z)-2-[3-Oxoisobenzofuran-1-(3H)-ylidene]acetates [Articolo su rivista]
Mancuso, Raffaella; Ziccarelli, Ida; Fini, Francesco; Della Ca', Nicola; Marino, Nadia; Carfagna, Carla; Gabriele, Bartolo
abstract

The first example of the oxidative carbonylation of 2-ethynylbenzoic acid derivatives, leading to alkyl (Z)-2-[3-oxoisobenzofuran-1-(3H)-ylidene]acetates in a regio- and stereoselective manner, is reported. Under the catalytic action of PdI 2 (2 mol%) in conjuction with KI (20 mol%), different 2-[(trimethylsilyl)ethynyl]benzoic acids were converted into the corresponding isobenzofuranones in high to excellent yields (70–98%). The proposed reaction mechanism involves syn 5-exo-dig cyclization, carbon monoxide insertion, and nucleophilic displacement by an alcohol. Desilylation occurred under the reaction conditions. The structure of a representative product, that is, methyl (Z)-2-[3-oxoisobenzofuran-1(3H)-ylidene]acetate, was confirmed by XRD analysis. (Figure presented.).

2019 - A technology platform to chiral amines: selected examples in asymmetric organocatalysis [Articolo su rivista]
Armando, Carlone; Fini, Francesco; Valeria, Nori; Arianna, Sinibaldi
abstract

Organocatalysis makes use of small organic molecules to activate reaction partners and is nowadays an established catalytic platform; in fact, despite the relatively young age, its potential and powerful impact is widely appreciated. Importantly, organocatalysis, along with metal- and biocatalysis, is routinely screened in industry during the selection process to target compounds of interest. Among these, chiral amines are one of the most important class of target molecules in industry. Herein we present selected approaches in organocatalysis to access chiral amines both from academia and industry.

2019 - Inhibition of Quorum Sensing-dependent biofilm formation and virulence factors in Pseudomonas aeruginosa by the boronic acid SM23 [Poster]
Peppoloni, S.; Pericolini, E.; Colombari, B.; Pinetti, D.; Fini, F.; Prati, F.; Blasi, E.; Caselli, E.
abstract

Introduction: Quorum sensing (QS) regulates the expression of virulence factors in P. aeruginosa. Inhibiting QS-controlled virulence factors without affecting the growth of P. aeruginosa may represent a promising strategy for overcoming its widespread and constantly increasing drug-resistance. In this study, we investigated the effects of SM23, a boronic acid, which was specifically designed as beta-lactamase inhibitor, on biofilm formation and virulence factor production by P. aeruginosa Material and Methods: the bioluminescent P. aeruginosa strain P1242 was employed. The effect of the boronic acid SM23 on P. aeruginosa were assessed by evaluating a) the biofilm formation and its morphology by crystal violet staining/bioluminescence and confocal microscopy and b) the production in cell supernatant of the virulence factors, pyoverdines and elastase. The pyoverdine release was assessed by measuring the fluorescence emission with a multi-well fluorescence plate reader and mass spectrometry, while the elastase activity was determined by the Ohman’s method, using the Elastin-Congo red as substrate. Finally a qRT-PCR was employed to study the SM23-induced changes in the expression of the QS genes lasI and lasR. Results: the SM23 significantly inhibited the development of biofilm and the production of virulence factors, as pyoverdines and elastase, without affecting bacterial growth. Preincubation of bacteria with P. aeruginosa-conditioned (24 h) medium completely prevented the binding of SM23 to the cells. By investigating the transcriptional changes related to QS, we found that Pseudomonas exposure to SM23 caused a notable decrease in the levels of lasI and lasR gene expression. Finally, the SM23 significantly reduced P. aeruginosa biofilm and pyoverdine production on endotracheal tubes, an in vitro condition closely mimicking clinical settings. Discussion and Conclusions: taken together, our results indicate that boronic acid SM23, besides inhibiting beta-lactamase, can also act as potent inhibitor of QS in P. aeruginosa, suggesting that it may have a potential application in the prevention and treatment of biofilm-associated P. aeruginosa infections.

2019 - Organocatalysis and beyond: Activating reactions with two catalytic species [Articolo su rivista]
Sinibaldi, A.; Nori, V.; Baschieri, A.; Fini, F.; Arcadi, A.; Carlone, A.
abstract

Since the beginning of the millennium, organocatalysis has been gaining a predominant role in asymmetric synthesis and it is, nowadays, a foundation of catalysis. Synergistic catalysis, combining two or more different catalytic cycles acting in concert, exploits the vast knowledge acquired in organocatalysis and other fields to perform reactions that would be otherwise impossible. Merging organocatalysis with photo-, metallo- and organocatalysis itself, researchers have ingeniously devised a range of activations. This feature review, focusing on selected synergistic catalytic approaches, aims to provide a flavor of the creativity and innovation in the area, showing ground-breaking examples of organocatalysts, such as proline derivatives, hydrogen bond-mediated, Cinchona alkaloids or phosphoric acids catalysts, which work cooperatively with different catalytic partners.

2018 - Diastereospecific Bis-alkoxycarbonylation of 1,2-Disubstituted Olefins Catalyzed by Aryl α-Diimine Palladium(II) Catalysts [Articolo su rivista]
Olivieri, Diego; Fini, Francesco; Mazzoni, Rita; Zacchini, Stefano; Della Ca', Nicola; Spadoni, Gilberto; Gabriele, Bartolo; Mancuso, Raffaella; Zanotti, Valerio; Carfagna, Carla
abstract

Readily synthesized aryl α-diimine derivatives have been used as efficient ligands for the palladium-catalyzed oxidative bis-alkoxycarbonylation reaction of 1,2-disubstituted olefins. The most active catalyst A was formed in situ from bis-(2,6-dimethylphenyl)-2,3-dimethyl-1,4-diazabutadiene and Pd(TFA)2 (TFA=trifluoroacetate). This catalytic system was able to selectively convert 1,2-disubstituted olefins into 2,3-disubstituted-succinic diesters with total diastereospecificity, in good yields (up to 97%) with 2 mol% of catalyst loading, under mild reaction conditions (4 bar of CO at 20 °C in presence of p- toluenesulfonic acid as additive and p-benzoquinone as oxidant). The optimized reaction conditions could be successfully applied to 1,2-disubstituted aromatic, aliphatic, cyclic olefins and to unsaturated fatty acid methyl esters, employing methanol or benzyl alcohol as nucleophiles. The use of the bulky, less reactive isopropyl alcohol has allowed to better understand the mechanisms involved in the catalytic process. The geometry of the carbonylated products can be explained as a consequence of a concerted syn addition of the Pd-alkoxycarbonyl moiety to the olefin C=C bond. Catalyst A was isolated, characterized and analyzed by single crystal X-ray diffraction analysis. (Figure presented.).

2018 - Inhibition of Acinetobacter -Derived Cephalosporinase: Exploring the Carboxylate Recognition Site Using Novel β-Lactamase Inhibitors [Articolo su rivista]
Caselli, Emilia; Romagnoli, Chiara; Powers, Rachel A.; Taracila, Magdalena A.; Bouza, Alexandra A.; Swanson, Hollister C.; Smolen, Kali A.; Fini, Francesco; Wallar, Bradley J.; Bonomo, Robert A.; Prati, Fabio
abstract

Boronic acids are attracting a lot of attention as β-lactamase inhibitors, and in particular, compound S02030 (Ki= 44 nM) proved to be a good lead compound against ADC-7 (Acinetobacter-derived cephalosporinase), one of the most significant resistance determinants in A. baumannii. The atomic structure of the ADC-7/S02030 complex highlighted the importance of critical structural determinants for recognition of the boronic acids. Herein, to elucidate the role in recognition of the R2-carboxylate, which mimics the C3/C4found in β-lactams, we designed, synthesized, and characterized six derivatives of S02030 (3a). Out of the six compounds, the best inhibitors proved to be those with an explicit negative charge (compounds 3a-c, 3h, and 3j, Ki= 44-115 nM), which is in contrast to the derivatives where the negative charge is omitted, such as the amide derivative 3d (Ki= 224 nM) and the hydroxyamide derivative 3e (Ki= 155 nM). To develop a structural characterization of inhibitor binding in the active site, the X-ray crystal structures of ADC-7 in a complex with compounds 3c, SM23, and EC04 were determined. All three compounds share the same structural features as in S02030 but only differ in the carboxy-R2 side chain, thereby providing the opportunity of exploring the distinct binding mode of the negatively charged R2 side chain. This cephalosporinase demonstrates a high degree of versatility in recognition, employing different residues to directly interact with the carboxylate, thus suggesting the existence of a "carboxylate binding region" rather than a binding site in ADC enzymes. Furthermore, this class of compounds was tested against resistant clinical strains of A. baumannii and are effective at inhibiting bacterial growth in conjunction with a β-lactam antibiotic.

2016 - Chemical–physical properties and cytotoxicity of N-decanoyl amino acid-based surfactants: Effect of polar heads [Articolo su rivista]
Perinelli, Diego R.; Casettari, Luca; Cespi, Marco; Fini, Francesco; Man, Dede K. W.; Giorgioni, Gianfabio; Canala, Silvia; Lam, Jenny K. W.; Bonacucina, Giulia; Palmieri, Giovanni F.
abstract

N-acyl amino acids-based surfactants are an attractive class of anionic amphiphiles alternative to sulphate-based surfactants, potentially employed as excipients for pharmaceutical applications in which an anionic surfactant is needed. Thus, a systematic characterization of their toxicological profile is required, particularly in comparison to sodium dodecyl sulphate (SDS), a widely employed surfactant in pharmaceutical formulations. This work reported a systematic study on the relationship between the structures of N-acyl amino acids-based surfactants, their physicochemical properties and toxicological profiles. N-Decanoyl aminoacids with different polar heads (leucine, methionine, serine and proline) were synthesized and characterized in terms of surface tension and aggregation properties. Different human cell lines (Caco-2, A549, Calu-3) and erythrocytes were selected as model for oral, respiratory or parenteral administration to evaluate surfactants cytotoxicity. Moreover, the ability of surfactants to interact with cell membranes was assessed by the Trans Epithelial Electrical Resistance (TEER). Results suggested that the different polar heads affect the aggregation state and cell toxicity profiles of surfactants, but not their surface properties. According to the toxicity assays, all N-decanoyl surfactants were less toxic than SDS, suggesting that hydrophilic interactions between amphiphiles and cell membranes play a key role in determining cellular toxicity.

2016 - Oxidative Alkoxycarbonylation of Alkynes by Means of Aryl alpha-Diimine Palladium(II) Complexes as Catalysts [Articolo su rivista]
Beltrani, Michela; Carfagna, Carla; Milani, Barbara; Mancuso, Raffaella; Gabriele, Bartolo; Fini, Francesco
abstract

The straightforward in situ synthesized bis(2,6-diisopropyl)acenaphthenequinonediimine palladium triflate catalyst was generally employed for both the mono-alkoxycarbonylation of terminal alkynes, and the bis-alkoxycarbonylation of 1,2-disubstituted alkynes by using mild reaction conditions [carbon monoxide pressure (PCO)=4 bar, temperature=20 °C]. Utilizing low catalyst loading (down to 0.5 mol%), a variety of propiolic esters were synthesized with good to excellent isolated yields. Most importantly the system was very efficient not only with methanol but also with a range of different alcohols, starting from the less hindered benzyl alcohol to the most hindered ones, such as isopropyl alcohol and tert-butyl alcohol. In addition, aromatic and aliphatic 1,2-disubstituted alkynes were converted into maleic acid derivatives, together with an acid-catalyzed isomerization reaction, showing modest to good selectivity and excellent combined yields. In particular 3-hexyne showed a satisfactory degree of selectivity for the maleic diesters of methanol and benzyl alcohol, obtaining the corresponding products with good isolated yields. (Figure presented.).

2016 - Palladium complexes with simple iminopyridines as catalysts for polyketone synthesis [Articolo su rivista]
Rosar, Vera; Dedeic, D.; Nobile, T.; Fini, Francesco; Balducci, Gabriele; Alessio, Enzo; Carfagna, Carla; Milani, Barbara
abstract

Four iminopyridines (N-N′) differing in the nature of the substituents on the iminic carbon and on the ortho positions of the aryl ring (H or CH3) on the iminic nitrogen were used for the synthesis of neutral and monocationic palladium(ii) complexes of general formulae [Pd(CH3)Cl(N-N′)] and [Pd(CH3)(NCCH3)(N-N′)][PF6]. The detailed NMR characterization in solution highlighted that: (i) for both series of complexes, the Pd-CH3 signal is progressively shifted to a lower frequency on increasing the number of methyl groups on the ligand skeleton; (ii) for the neutral derivatives, the chemical shift of the 15N NMR signals, determined through 1H,15N-HMBC spectra, is significantly affected by the coordination to palladium; (iii) the coordination induced shift (CIS) of the nitrogen atom trans to the CH3 ligand is smaller than the other. The structure in the solid state for the neutral derivatives with all the four ligands was solved, pointing out that: (iv) the Pd-C bond distance increases with the basicity of the nitrogen-donor ligand; (v) the Pd-N bond distance correlates well with the CIS value. The combining of the solution and solid state structural features allows stating that: (vi) the Pd-CH3 singlet is a good probe for the electron donor capability of the ligand; (vii) the CIS value might be used as a probe for the strength of the Pd-N bond. All monocationic complexes generated active catalysts for the CO/vinyl arene copolymerization, leading to prevailingly syndiotactic polyketones. The catalyst performances, both in terms of catalyst productivity and polymer molecular weight, correlate well with the precatalyst structural features.

2016 - Palladium(II)-Catalyzed Cross-Dehydrogenative Coupling (CDC) of N-Phthaloyl Dehydroalanine Esters with Simple Arenes: Stereoselective Synthesis of Z-Dehydrophenylalanine Derivatives [Articolo su rivista]
Bartoccini, Francesca; Cannas, Diego Maria; Fini, Francesco; Piersanti, Giovanni
abstract

Pd(II)-catalyzed cross-dehydrogenative coupling (CDC) of methyl N-phthaloyl dehydroalanine esters with simple aromatic hydrocarbons is reported. The reaction, which involves the cleavage of two sp(2) C–H bonds followed by C–C bond formation, stereoselectively generates highly valuable Z-dehydrophenylalanine skeletons in a practical, versatile, and atom economical manner. In addition, a perfluorinated product was expediently converted into important nonproteinogenic amino acid building blocks through copper-catalyzed conjugate additions of boron, silicon, and hydride moieties.

2015 - Catalytic oxidative carbonylation of amino moieties to ureas, oxamides, 2-oxazolidinones, and benzoxazolones [Articolo su rivista]
Mancuso, Raffaella; Raut, Dnyaneshwar S.; Della Ca, Nicola; Fini, Francesco; Carfagna, Carla; Gabriele, Bartolo
abstract

The direct syntheses of ureas, oxamides, 2-oxazolidinones, and benzoxazolones by the oxidative carbonylation of amines, β-amino alcohols, and 2-aminophenols allows us to obtain high value added molecules, which have a large number of important applications in several fields, from very simple building blocks. We have found that it is possible to perform these transformations using the PdI2/KI catalytic system in an ionic liquid, such as 1-butyl-3-methylimidazolium tetrafluoroborate, as the solvent, the solvent/catalyst system can be recycled several times with only a slight loss of activity, and the product can be recovered easily by crystallization.

2015 - Selective Aryl alpha-Diimine/Palladium-Catalyzed Bis-Alkoxy- carbonylation of Olefins for the Synthesis of Substituted Succinic Diesters [Articolo su rivista]
Fini, Francesco; Beltrani, Michela; Mancuso, Raffaella; Gabriele, Bartolo; Carfagna, Carla
abstract

Aryl alpha-diimine derivatives have been used, for the first time, as efficient new ligands for the palladium-catalyzed oxidative bis-alkoxycarbonylation reaction of olefins. The most active catalyst was formed in situ from bis(9-anthryl)-2,3-dimethyl-1,4-diazabutadiene and palladium(II) trifluoroacetate [Pd(TFA)2]. This catalytic system was able to selectively convert olefins into succinic diesters in good yields (up to 97%) and low catalyst loading (up to 0.5 mol%) under mild reaction conditions [4 bar of carbon monoxide (CO) at 20 °C in the presence of p-toluenesulphonic acid as additive and p-benzoquinone as oxidant]. The optimized conditions could be successfully applied to both aromatic and aliphatic olefins, by using methanol, benzyl alcohol or isopropyl alcohol

2015 - Toxicological profiles and surface properties at physiological pH of N-decanoyl amino acids [Abstract in Atti di Convegno]
Perinelli, Diego R.; Casettari, Luca; Cespi, Marco; Fini, Francesco; Man, Dede K. W.; Giorgioni, Gianfabio; Canala, Silvia; Lam, Jenny K. W.; Bonacucina, Giulia; Palmieri, Giovanni F.
abstract

Purpose. N-acyl amino acids based surfactants are an attractive class of anionic amphiphiles alternative to sulphate-based surfactants potentially employed as excipients in all pharmaceutical applications at which an anionic surfactant (eg. sodium dodecyl sulphate SDS) is needed [1, 2]. The aim of this work is to correlate surface properties of N-decanoyl amino acids at physiological pH and their toxicological profile in order to explore the potential use of these surfactants for pharmaceutical applications. Methods. A series of N-decanoyl amino acids with different polar heads (leucine, methionine, serine and proline) was synthesized and characterized in isotonic phosphate buffer pH 7.3 in term of surface properties and cell toxicity in comparison to SDS, a common and widely employed surfactant in pharmaceutical formulations. Three different cell lines (Caco-2, A549, Calu-3) and erythrocytes were selected as model for oral, respiratory or parenteral administration in order to evaluate surfactant cellular toxicity (MTT, LDH, hemolytic assay). Results. The different polar heads did not strongly affect surface properties of surfactants, differently to their cell toxicity profiles which were specifically influenced by the structure of the amino acid polar head. According to cell toxicity assays, all N-decanoyl surfactants resulted to be less toxic than SDS. In particular, cell viability (MTT assay) was found to be dependent on the hydrophobicity of the lateral group of the amino acid in all tested cell lines, while LDH and hemolytic assay highlighted the low effect of N-decanoyl amino acid on disrupting cell membranes. Conclusions. Overall, such results suggested that hydrophilic interactions between amphiphiles and cell membranes play a key role in determining cellular toxicity. [1]Pinazo A, Pons R, Ṕrez L, )nfante MR. . Industrial & Engineering Chemistry Research 50: 4805-17 [2]Moran MC, Pinazo A, Perez L, Clapes P, Angelet M, et al. 2004. Green Chemistry 6: 233-40

2015 - Unprecedented Comonomer Dependence of the Stereochemistry Control in Pd-Catalyzed CO/Vinyl Arene Polyketone Synthesis [Articolo su rivista]
Canil, Giovanni; Rosar, Vera; Dalla Marta, Silvia; Bronco, Simona; Fini, Francesco; Carfagna, Carla; Durand, Jérôme; Milani, Barbara
abstract

Two pyrene-tagged iminopyridines (N-N') were used to synthesize neutral and monocationic, palladium(II) complexes, [Pd(Me)Cl(N-N')] and [Pd(Me)(MeCN)(N-N')][PF6]. The monocationic complexes generated active catalysts in the CO/vinyl arene copolymerization, leading to polyketones with yields and molecular weight strongly dependent on N-N', with the ketimine catalysts one order of magnitude more productive than the aldimine counterpart. The stereochemistry of polyketones synthesized with the aldimine catalyst was found to be dependent on the vinyl comonomer: prevailingly syndiotactic copolymers were obtained for styrene, prevailingly isotactic copolymers were produced for 4-methyl styrene, and atactic macromolecules were formed for 4-tert-butyl styrene. The statistical analysis demonstrated that the control of the stereochemistry switched from enantioselective site control for 4-methyl styrene to a combination of chain-end and enantioselective site control for styrene.

2014 - Analogies and Differences in Palladium-Catalyzed CO/Styrene and Ethylene/Methyl Acrylate Copolymerization Reactions [Articolo su rivista]
Rosar, Vera; Meduri, Angelo; Montini, Tiziano; Fini, Francesco; Carfagna, Carla; Fornasiero, Paolo; Balducci, Gabriele; Zangrado, Ennio; Milani, Barbara
abstract

The catalytic CO/styrene and ethylene/methyl acrylate copolymerizations are compared for the first time by applying the same precatalysts. With this aim, PdII neutral, [Pd(CH3)Cl(N–N)], and monocationic, [Pd(CH3)(L)(N–N)][PF6] (L=CH3CN, DMSO), complexes with 1-naphthyl- and 2-naphthyl-substitued α-diimines with both an acenaphthene and a diazabutadiene skeleton as chelating nitrogen-donor ligands (N–N) have been studied. In the case of the complexes with the 1-naphthyl-substituted ligands, syn and anti isomers are found both in solid state and in solution. All the monocationic complexes generate active catalysts for the CO/styrene copolymerization leading to atactic or isotactic/atactic stereoblock copolymers depending on the ligand bonded to palladium. Instead, in the case of the ethylene/methyl acrylate copolymerization only the complexes with the 1-naphthyl-substituted ligands generate catalysts for this reaction.

2014 - New Aryl alpha-Diimine Palladium(II) Catalysts in Stereocontrolled CO/Vinyl Arene Copolymerization [Articolo su rivista]
Carfagna, Carla; Gatti, Giuseppe; Paoli, Paola; Binotti, Barbara; Fini, Francesco; Passeri, Alessandra; Rossi, Patrizia; Gabriele, Bartolo
abstract

The effect of the catalyst structure on the stereoselectivity of CO/vinyl arene copolymerization has been studied with the aim of developing catalytic systems able to improve the yields while maintaining the high degree of copolymer isotacticity previously obtained using achiral nitrogen ligands. Aryl alpha-diimine ligands having extended aromatic rings (Ar)2DABMe2, with Ar = 1-C10H7 (e), 1-C14H9 (f), 9-C14H9 (g), have been synthesized, and alpha-diimine coordination to cationic methylpalladium complexes has been investigated in solution, by means of NMR spectroscopy, and in the solid state for [Pd(Me)(NCMe)((9-C14H9)2DABMe2)][PF6] (2g). The performance of these catalysts in CO/vinyl arene copolymerization, under mild conditions, was analyzed in terms of productivity and degree of stereoregularity of the resulting polyketones. In comparison with previous results, a remarkable enhancement in the yield of isotactic copolymer was observed using the new achiral 9-anthryl alpha-diimine ligand g, confirming that the ortho disubstitution and the extended aromatic rings play key roles in obtaining good stereoselectivity and good productivity. To perform a structural analysis of the first steps of the CO/p-methylstyrene copolymerization, complex [Pd(Me)(CO)((9-C14H9)2DABMe2)][BAr′4] (3g) was used as a starting point: NMR investigation reveals the stereoselective formation of the olefin/CO/olefin insertion product (6g), which prevalently exists in solution in only one diastereoisomeric form, thus justifying the observed high polymer isotacticity.

2012 - Phase transfer catalyzed enantioselective cyclopropanation of 4-nitro-5-styrylisoxazoles [Articolo su rivista]
Del Fiandra, Claudia; Piras, Linda; Fini, Francesco; Disetti, Paolo; Moccia, Maria; Adamo, Mauro F. A.
abstract

Heavily substituted cyclopropane esters were prepared in high yields, complete diastereoselection and high (up to 96%) enantioselectivity. The reaction described herein entailed reacting 4-nitro-5-styrylisoxazoles, a class of cinnamate synthetic equivalent, with 2-bromomalonate esters under the catalysis of 5 mol% of a Cincona derived phase-transfer catalyst. The reaction allowed multi-gram preparation of desired products.

2011 - Catalytic Enantioselective Addition of Sodium Bisulfite to Chalcones [Articolo su rivista]
Moccia, Maria; Fini, Francesco; Scagnetti, Michela; Adamo, Mauro F. A.
abstract

At last! The addition of bisulfite to olefins, discovered over a century ago, remains the most straightforward approach to aliphatic sulfonic acids. A catalytic enantioselective procedure has now been realized that employs a bifunctional aminothiourea catalyst (see picture). Sulfonic acids were obtained from chalcones in high yields and high enantioselectivity and in both configurations.

2010 - Development of a Mild Procedure for the Addition of Bisulfite to Electrophilic Olefins [Articolo su rivista]
Fini, Francesco; Nagabelli, Murali; Adamo, Mauro F. A.
abstract

The sulfonylation of activated alkenes is an important yet unexplored reaction due to the harshness of conditions required. We have identi- fied a procedure which allowed the reaction of al- kenes with equimolar amounts of bisulfite at room temperature.

2009 - Asymmetric Synthesis of alfa-beta-Diaminophosphonic Acid Derivatives with a catalytic Enantioselective Mannich Reaction [Articolo su rivista]
Momo, Robert D.; Fini, Francesco; Bernardi, Luca; Ricci, Alfredo
abstract

Optically active alpha,beta-diaminophosphonic acid derivatives were obtained from the catalytic enantioselective Mannich reaction of phosphoglycine Schiff bases with N-Boc-imines, generated in situ from alpha-amido sulfones.

2009 - Catalytic Asymmetric Mannich Reactions of Sulfonylacetates [Articolo su rivista]
Cassani, Carlo; Bernardi, Luca; Fini, Francesco; Ricci, Alfredo
abstract

Arylsulfonylacetates can be viewed as synthetic equivalents of a variety of alpha-carboxylate anions. Phase-transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from alpha-amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of beta-amino acid derivatives.

2009 - Organocatalytic Asymmetric Formal [3 + 2] Cycloaddition with in Situ-Generated N-Carbamoyl Nitrones [Articolo su rivista]
Gioia, Claudio; Fini, Francesco; Mazzanti, Andrea; Bernardi, Luca; Ricci, Alfredo
abstract

A novel organocatalytic formal [3 + 2] cycloaddition reaction with in situ generation of N-carbamoyl nitrones is presented. For the first time, N-Boc- and N-Cbz-protected isoxazolidines have been directly obtained as single diastereoisomers in generally high yields and enantiomeric excesses using mild reaction conditions and inexpensive, readily available Cinchona alkaloid quaternary ammonium salts as catalysts. Synthetic manipulations of the products provided highly valuable building blocks such as free isoxazolidines, a N-Boc-1,3-aminoalcohol, and a free δ-lactam. This report represents a pioneering work in the use of N-carbamoyl nitrones as electron-poor 1,3-dipoles and glutaconates as new dipolarophiles in asymmetric catalysis.

2008 - An easy entry to optically active a-amino phosphonic acid derivatives using phase-transfer catalysis (PTC). [Articolo su rivista]
Fini, Francesco; Micheletti, Gabriele; Bernardi, Luca; Pettersen, Daniel; Fochi, Mariafrancesca; Ricci, Alfredo
abstract

The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active alpha-amino phosphonic acid derivatives directly from alpha-amido sulfones.

2008 - Organocatalytic Asymmetric Diels-Alder Reactions of 3-Vinylindoles [Articolo su rivista]
Gioia, Claudio; Hauville, Agnès; Bernardi, Luca; Fini, Francesco; Ricci, Alfredo
abstract

Diels or no Diels? A bifunctional organic catalyst based on the thiourea motif is able to coordinate both diene and dienophile in an unprecedented asymmetric Diels–Alder reaction of 3-vinylindole derivatives, giving a rapid access to optically active tetra- and hexahydrocarbazoles with excellent results in terms of yields, diastereoselectivities, and enantioselectivities.

2008 - Organocatalyzed Enantioselective Synthesis of Nitroalkanes Bearing All-Carbon Quaternary Stereogenic Centers through Conjugate Addition of Acetone Cyanohydrin [Articolo su rivista]
Bernardi, Luca; Fini, Francesco; Fochi, Mariafrancesca; Ricci, Alfredo
abstract

The first organocatalyzed phase-transfer enantioselective conjugate addition of cyanide ion derived from acetone cyanohydrin to beta,beta'-disubstituted nitroolefins is reported. The reaction leads to the efficient formation of nitroalkanes bearing an all-carbon quaternary stereogenic center in up to 72% ee.

2007 - Organocatalysis in the Asymmetric Synthesis of Nitrogen-Containing Compounds: How and Why [Articolo su rivista]
Bernardi, Luca; Fini, Francesco; Fochi, Mariafrancesca; Ricci, Alfredo
abstract

Various types of polyfunctionalised stereodefined organic molecules appear to be highly serviceable as organocatalysts in the asymmetric synthesis of nitrogen-containing compounds. Beyond name reactions such as the aza-Henry, the Friedel-Crafts, and the Strecker other representative transformations like the hydrophosphonylation can be easily approached by using the suitable organocatalytic species and are herein reported with a special emphasis placed on the reaction and stereochemical outcomes and on the mechanistic insights.

2007 - Organocatalytic Enantioselective Decarboxylative Addition of Malonic Half Thioesters to Imines [Articolo su rivista]
Ricci, Alfredo; Pettersen, Daniel; Bernardi, Luca; Fini, Francesco; Fochi, Mariafrancesca; Herrera, Raquel P.; Sgarzani, Valentina
abstract

We describe a biomimetic organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to imines. This simple protocol makes use of readily available Cinchona-derived organocatalysts and nucleophiles at the carboxylate oxidation state. The resulting beta-amino thioesters, being attractive precursors for the preparation of optically active beta-amino acids, are formed in good yields and in up to 79% ee. As suggested by several mechanistic insights the desired products are formed via initial formation of a thioester acetate enolate via decarboxylation of the malonic acid half thioester, followed by addition to the imine.

2007 - Organocatalytic Asymmetric Mannich Reactions with N-Boc and N-Cbz Protected alfa-Amido Sulfones (Boc: tert-Butoxycarbonyl, CBz: Benzyloxycarbonyl) [Articolo su rivista]
Marianacci, Olindo; Micheletti, Gabriele; Bernardi, Luca; FINI, Francesco; Fochi, Mariafrancesca; Pettersen, Daniel; Sgarzani, Valentina; Ricci, Alfredo
abstract

Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta3-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate–catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.

2007 - Organocatalytic asymmetric aza-Michael reaction: enantioselective addition of O-benzylhydroxylamine to chalcones. [Articolo su rivista]
Pettersen, Daniel; Piana, Francesca; Bernardi, Luca; Fini, Francesco; Fochi, Mariafrancesca; Sgarzani, Valentina; Ricci, Alfredo
abstract

A novel organocatalytic approach for aza-Michael reaction of chalcones using commercial and non-expensive O-benzyl-hydroxylamine and a readily available organocatalyst is provided. The use of this simple protocol results in beta-keto hydroxylamines in up to 60% ee, thus extending the generality of the catalytic enantioselective aza-Michael reaction.

2006 - A Broadened Scope for the Use of Hydrazones as Neutral Nucleophiles Using H-Bonding Organocatalysts [Articolo su rivista]
Pettersen, Daniel; Herrera, Raquel P.; Bernardi, Luca; Fini, Francesco; Sgarzani, Valentina; Fernandez, Rosario; Lassaletta, José M.; Ricci, Alfredo
abstract

Using thioureas as H-bonding organocatalysts, nitroalkenes can be activated for the conjugate addition of hydrazones as neutral nucleophiles. Formaldehyde derivatives react at the azomethine carbon as expected, whereas hydrazones from enolizable aldehydes behave as ene-hydrazines and react at the alpha-carbon instead. Ionic liquids were found to decrease the reaction times considerably compared to commonly used solvents, whereas alter- native activation by Lewis acids resulted in decomposition of reactants.

2006 - Direct Access to Enantiomerically Enriched alpha-Amino Phosphonic Acid Derivatives by Organocatalytic Asymmetric Hydrophosphonylation of Imines [Articolo su rivista]
Pettersen, Daniel; Marcolini, Mauro; Bernardi, Luca; Fini, Francesco; Herrera, Raquel P.; Sgarzani, Valentina; Ricci, Alfredo
abstract

A simple and efficient organocatalytic enantioselective hydrophosphonylation of imines to enantiomerically enriched alpha-amino phosphonates is reported. By using 10 mol % of quinine as the catalyst in the enantioselective addition of diethyl phosphite to N-Boc protected imines, alpha-amino phosphonates are obtained in moderate to good yields and with up to 94% ee.

2006 - Enantioselective aza-Henry reaction using cinchona organocatalysts [Articolo su rivista]
Bernardi, Luca; Fini, Francesco; Herrera, Raquel P.; Ricci, Alfredo; Sgarzani, Valentina
abstract

The aza-Henry reaction of imines with nitromethane was promoted by cinchona alkaloids and modified cinchona bases to give optically active beta-nitroamines. Various N-protected imines were examined as substrates. N-Boc, N-Cbz, and N-Fmoc protected imines gave the best results in terms of chemical yields and enantioselectivities. After a careful screening of a series of chiral bases, very good enantioselectivities up to 94% ee were obtained using a cinchona-based thiourea organocatalyst under the optimized reaction conditions.

2006 - First 1,3-Dipolar Cycloaddition of Azomethine Ylides With (E)-Ethyl 3-Fluoroacrylate. Regio- and Stereoselective Synthesis of Enantiopure Fluorinated Prolines. [Articolo su rivista]
Bonini, Bianca F.; Boschi, Francesca; Comes Franchini, Mauro; Fochi, Mariafrancesca; Fini, Francesco; Mazzanti, Andrea; Ricci, Alfredo
abstract

Enantiopure fluorinated prolines with four chiral centers were obtained from 1,3-dipolar cycloaddition of azomethine ylides and (E)-ethyl 3-fluoroacrylate.

2006 - Phase Transfer Catalyzed Enantioselective Strecker Reactions of alpha-Amido Sulfones with Cyanoydrins [Articolo su rivista]
Herrera, Raquel P.; Sgarzani, Valentina; Bernardi, Luca; Fini, Francesco; Pettersen, Daniel; Ricci, Alfredo
abstract

A study into the use of a chiral phase-transfer catalyst in conjunction with acetone cyanohydrin to effect the enantioselective formation of alpha-amino nitriles from alpha-amido sulfones is described. This novel catalytic asymmetric Strecker reaction is analyzed with regard to the possible mechanistic basis.

2006 - Phase-Transfer-Catalyzed Enantioselective Mannich Reaction of Malonates with alpha-Amido Sulfones [Articolo su rivista]
Fini, Francesco; Bernardi, Luca; Herrera, Raquel P.; Pettersen, Daniel; Ricci, Alfredo; Sgarzani, Valentina
abstract

The highly enantioselective reaction between in situ generated, Cbz-protected azomethines and malonates in the presence of 150 mol% of potassium carbonate (50% w/w) and 1 mol% of quinine-derived quaternary ammonium bromides as phase-transfer organocatalysts has been developed. This study reports a novel approach for the asymmetric Mannich-type reaction and a wide range of azomethines, including those derived from enolizable aldehydes, is tolerated by the present system. The adducts, obtained in excellent yields with ee up to 98%, are suitable precursors of optically pure beta-amino acids.

2006 - Towards the Synthesis of Highly Functionalized Chiral alpha-Amino Nitriles by Aminative Cyanation and Their Synthetic Applications [Articolo su rivista]
Bernardi, Luca; Bonini, Bianca F.; Capitò, Elena; Comes Franchini, Mauro; Dessole, Gabriella; Fini, Francesco; Fochi, Mariafrancesca; Herrera, Raquel P.; Ricci, Alfredo
abstract

The cyanobis(dibenzylamino)borane-mediated transformation of chiral aldehydes into the corresponding alpha-amino nitriles is described. Starting from these compounds short synthetic routes can be envisaged for obtaining diastereomerically pure functionalized 1,2-diamines and hydroxylated alpha-amino acids that are of interest as core key units of biologically active substances or as potential ligands for asymmetric catalysis. The stereochemical outcome of the aminative cyanation reaction is discussed.

2005 - Chiral oxazoline-1,3-dithianes: new effective nitrogen–sulfur donating ligands in asymmetric catalysis [Articolo su rivista]
Capitò, Elena; Bernardi, Luca; Comes Franchini, Mauro; Fini, Francesco; Fochi, Mariafrancesca; Pollicino, Salvatore; Ricci, Alfredo
abstract

A series of new chiral oxazoline-1,3-dithianes has been easily synthesized and used as ligands for asymmetric catalysis. The conjugate addition of Et2Zn to enones resulted in ees of up to 69%, whereas the Pd-catalyzed allylic alkylation led to the expected products in almost quantitative yields and up to 90% enantioselectivity. The ligand's conformation has been explored using a combination of X-ray and NMR measurements, indicating the presence of a remarkable anomeric effect, which accounts for the preference of the oxazoline ring for the axial location.

2005 - Phase-Transfer-Catalyzed Asymmetric Aza-Henry Reaction Using N-Carbamoyl Imines Generated In Situ from alpha-Amido Sulfones [Articolo su rivista]
Fini, Francesco; Sgarzani, Valentina; Pettersen, Daniel; Herrera, Raquel P.; Bernardi, Luca; Ricci, Alfredo
abstract

A general approach to the catalytic asymmetric aza-Henry reaction has been developed. The combination of a commercially available phase-transfer catalyst (PTC) with a base is able to promote the in situ formation of N-carbamoyl imines from α-amido sulfones and activate nitromethane towards the asymmetric addition reaction, thus furnishing N-carbamoyl-protected β-nitroamines in good yields and with up to 98 % ee (see scheme; PG=protecting group).