New Chiral Bifunctional Iminophosphorane Squaramide Organocatalysts: Synthesis and Application in the Enantioselective Michael Addition Patricia Camarero Gonzales, Francesca Franco, Laura Maria Raimondi, Alessandra Puglisi, Wafda Rabbani, Maurizio Benaglia Synthesis Germany, 2026 The design and the synthesis of new enantiopure squaramide-based bifunctional iminophosphorane catalysts are reported. Starting from readily available starting materials, such as squarate and (S)-tert-leucinol, the synthetic approach involved the construction of a squaramide featuring an azide group, as precatalyst, which is easily stored, not sensible to moisture, and highly manageable. The chiral iminophosphorane organocatalysts (generated in situ by simple addition of a phosphine to the azide) were tested in the enantioselective Michael addition of α-nitro esters to enones and promoted the reaction in up to 90% yield and 60% e.e. The products are valuable precursors of α,α-disubstituted amino acids, important building blocks in the preparation of highly functionalized molecules. The synthesis of an α-methyl-substituted proline derivative was demonstrated.
Long-term efficacy and safety of Control-IQ technology in younger children with type 1 diabetes in Italy (2020–2023): a longitudinal multicentre real-world study Valentino Cherubini, Roberto Franceschi, Andrea Fargalli, Marta Bassi, Riccardo Bonfanti, Giulia Bracciolini, Barbara Felappi, Riccardo Foglino, Dario Iafusco, Anna Lasagni, Bruno Bombaci, Claudio Maffeis, Giulio Maltoni, Chiara Mameli, Enza Mozzillo, Nicola Minuto, Barbara Piccini, Lara Devilli, Giulia Pezzino, Carmelo Pistone, Elena Prandi, Ivana Rabbone, Andrea Scaramuzza, Sara Santarelli, Francesca Silvestri, Riccardo Schiaffini, Valentina Tiberi, Davide Tinti, Marco Marigliano, Rosaria Gesuita, Donatella Lo Presti, Elvira Piccinno, Francesca Franco, Valeria De Donno, Petra Reinstadler, Silvia Sordelli, Vanna Graziani, Rosalia Roppolo, Anna Giulia Lambertini, Barbara Predieri, Emioli Randazzo, Elisabetta Delduca, Benedetta Vestrucci, Marilea Lezzi, Maurizio Delvecchio, Antonio Iannilli Eclinicalmedicine, 2026 Background: Automated insulin delivery (AID) systems have demonstrated significant improvements in glycemic control in children and adults with type 1 diabetes, but long-term real-world data in preschool-aged children remain limited, particularly in Europe, where Control-IQ is not approved for children under 6 years. This study aimed to evaluate the long-term effectiveness and safety of the t:slim X2 insulin pump with Control-IQ technology in children aged 0.5-5 years compared with those aged 6-10 years in a real-world multicenter Italian cohort. Methods: In this longitudinal, observational study conducted from 2020 to 2023, data were collected from 32 Italian centers on children <11 years diagnosed with type 1 diabetes for at least six months and using the t:slim X2 with Control-IQ technology (CIQ). Participants were grouped into 0.5-5 years or 6-10 years at CIQ initiation. Primary endpoints were the percentage of time spent in range (TIR, 70-180 mg/dL) and in tight range (TITR, 70-140 mg/dL) in the two age groups, evaluated according to children's demographic, socioeconomic, and clinical characteristics using mixed-effects models for repeated measures. Findings: We evaluated 253 children with 18-month follow-up, 131 into the 0.5-5-year group and 122 in the 6-10-year group. In the 0.5-5-year group, TIR and TITR increased significantly from baseline to 6 months and were then maintained through 18 months. In the 6-10-year group, similar improvements were observed, with no statistically significant differences between age groups in the TIR or TITR trajectories. In the adjusted mixed-effects models, TIR increased from baseline to 6 months by 5.45% (95% CI 3.78-7.11) and TITR increased by 5.56% (95% CI 3.60-7.51), with stabilization thereafter. Children of parents with a high level of education had a significantly greater mean TIR. A longer interval between T1D diagnosis and CIQ initiation was associated with a lower mean TITR (-1.21%, 95% CI -2.32 to -0.10). During observation, there were no episodes of severe hypoglycemia in younger children and only one episode in a 6-10-year-old. One episode of DKA occurred after the start of CIQ in a younger child. Interpretation: CIQ was associated with sustained improvements in glycemic outcomes, especially within the first six months. Adverse events were rare. These findings support potential supervised off-label use in young children. Funding: No specific funds were received for this study.
α,β-Unsaturated (Bis)Enones as Valuable Precursors in Innovative Methodologies for the Preparation of Cyclic Molecules by Intramolecular Single-Electron Transfer Tommaso Benettin, Francesca Franco, Fabrizio Medici, Sergio Rossi, Alessandra Puglisi Molecules, 2026 The synthesis of monocyclic and bicyclic compounds plays a fundamental role in organic chemistry, and the need for novel synthetic methodologies is still under investigation. In particular, α,β-unsaturated (bis)enones have emerged as valuable precursors for the formation of cyclic (both mono and bicyclic) structures through single-electron transfer (SET) processes. Single-electron transfer (SET) is a redox process where one electron moves from a donor species to an acceptor, generating radical ions or neutral radicals that drive unique reaction pathways. Thanks to the advent of radical chemistry, it was possible to discover an entirely new reactivity of α,β-unsaturated (bis)enones, which, after a SET event, undergo the formation of cyclic molecules, both in intra and inter-molecular reactions, under several possible pathways, including formal [2+2] cycloaddition reaction (22CA) and 5-exo-trig cyclization, for ring closure. Today, the generation of radical species can be broadly classified into three main approaches: photochemical and photocatalytic, metal-driven and electrochemical processes. In this review, we summarize the progress achieved to date in the synthesis of cyclic molecules from α,β-unsaturated (bis)enones via single-electron transfer events under these three main classes of processes. Whenever possible, the reaction pathway and fate of the radical species generated through SET is discussed.
Asymmetric Organocatalytic Addition of Malononitrile to Trifluoromethyl Arylketimines: A Viable Entry to Chiral α-CF3 Quaternary Aminoesters Milena Ivkovic, Francesca Franco, Sergio Rossi, Sara Ferrario, Alessandra Puglisi, Maurizio Benaglia Molecules, 2026 In the present study the stereoselective addition of malononitrile to trifluoromethyl arylketimines promoted by chiral iminophosphoranes was investigated. A panel of structurally diverse enantiopure bifunctional superbases, which include thiourea or squaramide unit and a basic site connected by a chiral scaffold, was tested in the asymmetric organocatalytic reaction, to afford an adduct featuring a quaternary stereocenter, in up to a 87/13 enantiomeric ratio. The product was then converted in a single step transformation into the corresponding enantioenriched α-CF3 substituted quaternary aminoester, without any loss of stereochemical integrity. The absolute configuration of the final product was established by chemical correlation of the chiral compound with a known molecule. Preliminary computational studies were performed in order to elucidate the reaction mechanism and rationalize the stereochemical outcome of the reaction.
Light-Driven Stereoselective Aryl Bisenone Cycloaddition: A Metal-Free Strategy for the Construction of Functionalized Pyrrolidines and Tetrahydrofurans Maurizio Benaglia, Francesca Franco, Tommaso Benettin, Fabrizio Medici, Sergio Rossi, Simonetta Resta, Alessandra Puglisi Synopen, 2026 In this study, we report an exploratory study on the reductive cyclization of nitrogen- and oxygen-containing aryl bisenones, enabling the efficient synthesis of highly functionalized pyrrolidines and tetrahydrofurans under visible light irradiation. The transformation proceeds through a photocatalytic cyclization promoted by catalytic amounts of Eosin Y, with Schreiner’s thiourea and Hantzsch ester acting as mediators under visible green light irradiation. The transformation is stereoselective and affords the five-membered heterocycle as a single, trans isomer. Moreover, the introduction of chiral oxazolidinone auxiliaries onto aryl bisenone precursors allowed the formation of chiral, highly substituted trans pyrrolidines and tetrahydrofurans in good yields, although with modest stereoselectivities.
Metallaphotoredox Deoxygenative Arylation of Alcohols: A Viable Strategy for the Synthesis of Tryptamine Derivatives Davide Gariboldi, Jacopo Brucoli, Alessandra Puglisi, Francesca Franco, Laura Raimondi, Maurizio Benaglia Chemcatchem, 2025 A metallaphotoredox deoxygenative arylation of alcohols strategy has been applied to prepare in a one pot procedure tryptamine derivatives. Starting from 3‐Br indoles and 2‐amino alcohols, in the presence of an Ir photocatalyst and catalytic amounts of NiBr2, 3‐(2‐aminoethyl)‐substituted indoles have been synthesized in up to 76% yield after 2 h under blue LED irradiation. Improved productivity and space time yield were observed when continuous flow technologies were employed (60% yield with 30 min residence time).
Nitrogen-Centered Radicals in Visible-Light-Promoted Reactions Francesca Franco, Monica F. Boselli, Fabrizio Medici Synopen, 2024 Nitrogen-centered radicals (NCRs) have been known in the literature since the beginning of the 1900s, but only with the spread of photoredox catalysis, and in particular visible-light-mediated radical processes, has nitrogen-radical chemistry become more accessible via the in situ generation of such radicals under mild conditions. Historically, unlike their carbon counterparts, nitrogen radicals were not utilized widely in academia or industry due to a lack of efficient strategies for their production. Nowadays, NCRs are more established, and this graphical review highlights key publications from the literature, categorizing them by both the type of NCR and the type of reaction. Such nitrogen radicals can be divided into four different categories according to their electronic configuration, orbital structure and chemical behavior. Additionally, the reactivity of these radicals is mostly exploited via four main types of process: (i) intramolecular cyclization, (ii) intramolecular hydrogen atom abstraction, (iii) Norrish type I fragmentation, and (iv) intermolecular addition to π systems.
Organocatalytic Asymmetric Reduction of δ-Nitro Dienes: a Viable Entry to Functionalized Amines and Highly Substituted Enantioenriched Cyclopentanes Chiara Faverio, Francesca Franco, Giulia Taini, Laura Raimondi, Maurizio Benaglia European Journal of Organic Chemistry, 2024 δ‐nitro dienes were successfully synthesized and converted to δ‐nitro alkenes with complete chemo and regioselectivity. The enantioselective organocatalytic reduction was also accomplished and afforded the product in up to 97 % e.e. The chiral nitro alkene was further elaborated and employed as starting material in a stereoselective cyclization reaction that led to an almost enantiomerically pure highly functionalised cyclopentane featuring 5 contiguous stereocenters.
Catalytic Enantioselective Entry to Triflones Featuring a Quaternary Stereocenter Francesca Franco, Sara Meninno, Jacob Overgaard, Sergio Rossi, Maurizio Benaglia, Alessandra Lattanzi Organic Letters, 2022 A highly enantioselective one-pot synthesis of functionalized triflones, bearing a quaternary stereocenter, has been developed, exploiting the Michael reaction of α-(trifluoromethylsulfonyl) aryl acetic acid esters with N-acryloyl-1H-pyrazole catalyzed by commercially available Takemoto’s catalyst, followed by nucleophilic acyl substitution with alcohols. Preliminary investigations highlighted the attractive potential of the triflinate anion as the leaving group for stereocontrolled postfunctionalizations.
