Domenico Albanese

A practical four-step sequence for the synthesis of α,δ-dioxoesters with high enantiomeric excess was developed. It makes use of a regio- and stereoselective Michael addition of a chiral ketimine to ethyl 2-(phenylthio)-2-propenoate as a key transformation. The synthetic elaboration of the Michael adduct provides the new ethyl 3-(1-methyl-2-oxo-cyclohexyl)-2-oxopropanoate, bearing a quaternary stereocenter with 95% ee and high yield.

Polyamidoamines obtained through the polyaddition of natural alpha-aminoacids to N,N′-methylenebisacrylamide were shown to be remarkably active flame retardants for cotton. The presence of a disulfide linkage together with phosphorus atoms was previously chosen as desirable structural requirements and added to the polymer chain for their flame retardants properties. The conjugation of cystamine with diethyl vinyl phosphonate to obtain the desired monomer is accompanied by the formation of a by-product that must be identified and characterized to optimize the reaction. The ability of nuclear magnetic resonance to detect and quantify the components of a mixture in solution has become increasingly important in the analysis of manufacturing processes. Here, we have used NMR spectroscopy to identify and quantify an impurity in the synthesis of the precursor of a flame retardant without removing the main product from solution. 1D and 2D NMR spectra were used to obtain the identification and full characterization of the molecules and the by-product was identified through the analysis of different nuclei, such as ¹H, ¹³C, ¹⁵N and ³¹P. Graphical abstract

Ammonium dihydrogenphosphate is the main ingredient of ABC powders used for widespread portable fire extinguishers. Rules in force today state the powder should be disposed of as a waste at the end of life (a few years depending on local regulations). However, phosphorous is nowadays recognized as one of the critical elements, in particular as regards to social balance and planet development, therefore new procedures to recycle the powder would be desirable to preserve this element. Although some examples of the reuse of ABC powders as fertilizers or flame retardants have been described, additional resources are consumed to remove powder additives. Therefore, it would be more sustainable to recycle the powder directly, once its desired properties have been verified. Herein, we describe some results that suggest the possibility to reuse the powder from a circular economy perspective.

Phase Transfer Catalysis (PTC) is a powerful tool to perform reactions in a practical fashion, both in laboratory and industrial scale. Significant cost savings and major process improvements can be achieved in reactions performed under PTC conditions. In the last few years remarkable results in stereoselective reactions were achieved using chiral, non‐racemic quaternary ammonium salts. Moreover, the use of bulky, chiral phosphate anions paired with achiral cations to generate lipophilic ion pairs allowed to design new avenues for the stereoselective construction of important building blocks. Hydrogen bond interactions were also shown to provide new pathways for asymmetric nucleophilic substitutions using insoluble reagents under PTC conditions. This Review will focus on recent advances in developing practical synthetic routes to construct molecules in a stereoselective fashion under PTC conditions.

A novel polyamidoamine (M-PCASS) bearing a disulfide group and two phosphonate groups per repeat unit was obtained by reacting N,N′-methylenebisacrylamide with a purposely designed bis-sec-amine monomer, namely, tetraethyl(((disulfanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(phosphonate) (PCASS). The aim was to ascertain whether the introduction of phosphonate groups, well-known for inducing cotton charring in the repeat unit of a disulfide-containing PAA, increased its already remarkable flame retardant efficacy for cotton. The performance of M-PCASS was evaluated by different combustion tests, choosing M-CYSS, a polyamidoamine containing a disulfide group but no phosphonate groups, as a benchmark. In horizontal flame spread tests (HFSTs), M-PCASS was a more effective flame retardant than M-CYSS at lower add-ons with no afterglow. In vertical flame spread tests, the only effect was afterglow suppression with no self-extinguishment even at add-ons higher than in HFSTs. In oxygen-consumption cone calorimetry tests, M-PCASS decreased the heat release rate peak of cotton by 16%, the CO₂ emission by 50%, and the smoke release by 83%, leaving a 10% residue to be compared with a negligible residue for untreated cotton. Overall, the set of results obtained envisage that the newly synthesized phosphonate-containing PAA M-PCASS may be suitable for specific applications as flame retardant, where smoke suppression or reduction of total gas released is a key requirement.

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu₄N⁺HSO₄^– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials.

Cascade reactions catalyzed by immobilized multi enzymatic systems are emerging as a tool to address the increasing need for green and sustainable chemistry. In this regard, the carrier-free immobilization strategy of combined cross-linked enzymes aggregates (combi- CLEAs) is of great interest. In a combi-CLEAs two or more enzymes are co-immobilized into a single unit where they are accommodated in close proximity in order to minimize the intermediates diffusion in the reaction medium, at the same time allowing the access of substrates and coenzymes to the active sites. The use of CLEAs provides a simple and low cost methodology that enhances operational and storage enzyme stability and facilitates biocatalyst recovery and recycle. Some significant applications of cascade reactions catalyzed by combi- CLEAs are reported in this mini-review. These examples have been applied on a multigram scale and have furnished practical steps towards the implementation of enzymes on an industrial scale.

Herein we present the first example of synthesis of 3,4-dihydropyran-2-ones from cinnamic thioesters via a stereoselective phase-transfer catalysed domino Michael-cyclisation reaction with acetylacetone. The reaction proceeded under the catalysis of Cinchona-derived quaternary ammonium phenoxide that in combination with inorganic bases provided 3,4-dihydropyran-2-ones in yields of up to 93% and enantioselectivities of up to 88% ee.

The N-heterocyclic carbene(NHCs)-catalyzed aza-benzoin condensation reaction is an efficient, single step strategy which employs easily available substrates, such as aldehydes and imines, to provide α-amino ketones. The multifunctionality and high reactivity of α-amino ketones makes these structures attractive for medicinal chemistry and as precursors of a variety of amine derivatives. The different electrophilic characteristics of aldehydes and imines ensure a high regioselective reaction. Enantiomerically-enriched α-amino ketones have been synthesized through stereoselective couplings promoted by chiral N-heterocyclic carbenes. One-pot domino procedures, including an aza-benzoin step, allow valuable complex molecules to be accessed.