ORGANIC SYNTHESIS & CATALYSIS
(principal researcher, prof. Giorgio Della Sala)
The chemical-physical properties and the biological activity of chiral molecules are strongly affected by their absolute and relative configuration. It follows that stereoselective catalysis, the area of research that studies and exploits the property of catalysts to control the configuration of reaction products, is of paramount importance in various industrial fields such as pharmaceutical, agrochemical, food, polymer and others. Although the second half of 20th century was dominated by transition-metal based catalysts, the increasing demand for environmetally benign processes encouraged, since the turn of the millenium, the extraordinary development of metal-free techniques such as organocatalysis and phase-transfer catalysis (PTC).
In this context, our efforts are directed to the development of novel organocatalyzed and phase-transfer catalyzed methodologies, with an eye on reduction of environmental impact, costs and energy consumption.
Catalytic macrocyclic peptidomimetics and derivatives
Cyclic peptoids (N-alkyl-glycine cyclic oligomers) are conveniently accessible through versatile solid-phase transfer methods, controlling the ring size and the structure of single monomers. We first demonstrated that cyclic peptoids behave as effective phase-transfer catalysts (Org. Biomol. Chem., 2013, 11, 726), and later we reported the enantioselective PTC alkylation of a-amino acid derivatives (J. Org. Chem., 2016, 81, 2494; Eur. J. Org. Chem. 2014, 7793; Synthesis, 2017, 49, 1319).
Cyclic peptoids are also useful precursors of macrocyclic polyamines. We demonstrated that the latter are valuable catalysts for the ring-opening polymerization (ROP) of lactide (Catal. Sci. Technol., 2025, 15, 71).
Stereoselective synthesis of phthalides
Phthalides are characterized by an aromatic lactone bicyclic motif that is incorporated into the structure of many natural products and analogs exhibiting relevant biological activity. During our studies we developed efficient methodologies, mainly based on PTC, for the stereoselective formation of C‒C bonds at the γ-carbon of the lactone ring (Org. Lett., 2017, 19, 4383; Chem. Eur. J., 2019, 25, 7131; J. Org. Chem., 2020, 85, 7476), which were then applied to the enantioselective synthesis of related secondary metabolites and drugs (Adv. Synth. Catal., 2024, 366, 1636; J. Org. Chem., 2024, 89, 7255).
Stereoselective synthesis of fluorine-containing compounds
The interest in the synthesis of fluorine-containing compound has grown exponentially in recent decades, with industrial applications in the areas of materials, pharmaceuticals, cosmetics and agrochemicals. The development of novel strategies for the regio- and/or stereoselective introduction of fluorinated functional groups is an hot topic in organic synthesis today. Our efforts led to the enantioselective trifluoromethylthiolation of alpha and beta-amino acid derivatives (Org. Lett., 2020, 22, 219; Org. Biomol. Chem., 2020, 18, 2914).
Other organocatalyzed and phase-transfer catalyzed reactions
Other works in asymmetric organocatalysis have involved the desymmetrization of meso-aziridines (Org. Lett., 2009, 11, 3330; Org. Biomol. Chem., 2011, 9, 6205; Tetrahedron, 2013, 69, 50), the conjugated beta-azidation of electron-poor alkenes (Adv. Synth. Catal., 2015, 357, 3365; Adv. Synth. Catal., 2019, 361, 4790), and the phase-transfer catalyzed vinylogous Michael addition of silyloxyfuran (J. Org. Chem., 2017, 82, 6629).
