Serena Perrone

Carbonylation reactions represent a powerful strategy in synthetic chemistry, because they enable the straightforward incorporation of carbonyl functionalities into organic substrates through transition‐metal catalysis in the presence of various nucleophiles. Traditionally, these transformations have been conducted under high pressures of carbon monoxide (CO), a lethal gas, and have relied on volatile organic solvents (VOCs) that are often toxic and derived from petroleum resources, thereby raising significant environmental and safety concerns. In line with the principle of green chemistry, this review summarizes recent advances in carbonylation reactions based on organic and inorganic CO surrogates that safely generate CO on demand within the reaction system, with a specific focus on strategies combining safer CO sources and green solvents classified as more sustainable alternatives to conventional VOCs according to the GSK solvent selection guide.

This study outlines the sustainable synthesis of novel hydroxytyrosol (HT) and tyrosol (T) ester derivatives via a Pd-catalyzed alkoxycarbonylation of aromatic iodides. The high sustainability of the process is attributed to the use of (1) a solid carbon monoxide source, Mo(CO)₆, in place of dangerous gaseous CO; (2) a biomass-derived organic solvent, CPME (cyclopentyl methyl ether); (3) naturally occurring hydroxylated compounds, such as HT and T, which could be derived from agricultural waste rather than produced from petroleum-based sources. The method enables the regioselective preparation of various HT and T esters in a short reaction time (4–8 h), under mild temperatures (80 °C), and with moderate-to-excellent yields (62–93%). Moreover, in vitro biological tests have demonstrated that, in addition to the well-known antioxidant properties typical of natural phenolic compounds such as HT and T, some of the newly synthesized derivatives have a safe profile and are effective inhibitors of the α-glucosidase with potential application in the management of hyperglycemia. This synthetic approach offers a promising strategy for exploring biologically relevant chemical space, bridging the gap between natural products and sustainable drug synthesis.

Polymeric materials are widely used in every human endeavor (bottles, clothes, containers, toys, tools, etc.) due to their unique properties of chemical and mechanical resistance. They are, however, almost non-biodegradable, and their chemical recycling into monomers is difficult and costly, thereby allowing their accumulation into the environment. This review highlights recent advances in the use of deep eutectic solvents (DESs) as catalysts and/or green solvents in plastics degradation, with the aim of designing greener processes for polymers’ chemical recycling, by reusing their monomers. These greener processes, in combination with other catalytic approaches, are aimed at introducing plastics as feedstock into the synthesis of other materials, according to the circular economy principles.

The Pd‐catalyzed amino‐ and alkoxycarbonylation of aryl iodides has been exploited, for the first time, in a bioinspired Deep Eutectic Solvent and under gas‐free conditions, by using Mo(CO)₆ as the CO source. The method allows for the preparation of carboxylic amides and esters in high yields (up to 99 %), short reaction time (2 h) and under mild reaction conditions (80 °C), with a low catalyst loading (2.5 mol %). Noteworthy, in the case of N‐hexylbenzamide, it has been demonstrated that both the catalyst and DES can be used for four consecutive runs, with a moderate decrease of catalytic efficiency. The methodology has been also applied to the preparation of an Active Pharmaceutical Ingredient used for the treatment of human scabies and lice.

A gas-free alkoxycarbonylation of aryl iodides was performed in MePh ₃ PBr/ethylene glycol DES by using Mo(CO) ₆ as a safe source of CO. The reaction occurred under mild reaction conditions (80 °C) and with a low catalyst loading (0.5 mol%).

A new 2-amino imidazole derivative, 5-(4-chlorophenyl)-N,1-di-o-tolyl-1H-imidazole-2-amine (3), has been synthesized using a green approach. The reaction was conducted in a ChCl (cholinium chloride)/urea eutectic mixture, which is a nature-inspired and environmentally friendly reaction medium. The proposed reaction mechanism involves the preliminary regioselective alkylation of the N_sp2 of guanidine (2), followed by an intramolecular condensation between the carbonyl moiety and the secondary N′_sp3. Finally, a tautomerization/aromatization step furnished the final product (3). Notably, 2-amino imidazole (3) could be isolated in high yield (91%), just by filtration from the DES/water mixture and subsequent crystallization; the remaining ChCl/urea could be recycled, after water removal, for four consecutive reactions without any significant drop in the (3) yield. The product has been fully characterized by ¹H, ¹³C, 2D ¹H-¹³C HSQC, and 2D ¹H-¹³C HMBC NMR; FT-IR spectroscopy; and EI-MS spectrometry.

A chemo- and stereoselective Pd-catalysed semi-reduction of alkynes to (Z)-alkenes has been performed in a phosphonium-based DES by using the in situ generation of H₂ from Al/H₂O. The antitumor agent combretastatin A4 has been also synthesized.

The synthesis of heterocycles is a fundamental area of organic chemistry that offers enormous potential for the discovery of new products with important applications in our daily life such as pharmaceuticals, agrochemicals, flavors, dyes, and, more generally, engineered materials with innovative properties. As heterocyclic compounds find application across multiple industries and are prepared in very large quantities, the development of sustainable approaches for their synthesis has become a crucial objective for contemporary green chemistry committed to reducing the environmental impact of chemical processes. In this context, the present review focuses on the recent methodologies aimed at preparing N-, O- and S-heterocyclic compounds in Deep Eutectic Solvents, a new class of ionic solvents that are non-volatile, non-toxic, easy to prepare, easy to recycle, and can be obtained from renewable sources. Emphasis has been placed on those processes that prioritize the recycling of catalyst and solvent, as they offer the dual benefit of promoting synthetic efficiency while demonstrating environmental responsibility.

The synthesis of a novel uracil derivative, 3-cyclohexyl-6-phenyl-1-(p-tolyl)pyrimidine-2,4(1H,3H)-dione (4), is reported via a four-component reaction involving an α-chloroketone (1), an aliphatic isocyanate (2), a primary aromatic amine (3) and carbon monoxide. The proposed reaction mechanism involves a Pd-catalyzed carbonylation of 2-chloro-1-phenylethan-1-one (1), leading to a β-ketoacylpalladium key intermediate, and, at the same time, in situ formation of non-symmetrical urea deriving from cyclohexyl isocyanate (2) and p-toluidine (3). After a chemo-selective acylation of the non-symmetrical urea and the subsequent cyclization of the acylated intermediate, 3-cyclohexyl-6-phenyl-1-(p-tolyl)pyrimidine-2,4(1H,3H)-dione (4) is formed. Uracil derivative 4 was isolated in good yield (73%) and fully characterized by ¹H, ¹³C, 2D ¹H-¹³C HSQC and 2D ¹H-¹³C HMBC NMR, FT-IR spectroscopy and GC-MS spectrometry.