Soufiane Touil

Herein, we report an efficient, fast, and green approach to synthesize γ‐phosphonyloximes ( 2 ) via microwave‐assisted oximation of γ‐phosphonylketones under solvent‐free conditions. This method achieved high yields (up to 95%) in just 5 min. Subsequent O‐acetylation of these oximes yielded novel O ‐acetyloxime derivatives ( 3 ). Structural characterization of all the synthesized compounds was performed using FT‐IR, NMR ( ¹ H, ^{3 1} P, and ^{1 3} C), mass spectrometry, and x‐ray crystallography (for 2a ), confirming their configuration as mixtures of E / Z isomers with predominant E‐forms. The antibacterial activity was evaluated against Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhimurium) strains. The O‐acetylated compounds ( 3 ) exhibited superior activity compared to their oxime precursors ( 2 ), with 3a identified as the most potent agent (MIC = 20–40 µg/mL). Molecular docking studies against E. coli FabH enzyme revealed that 3a binds deeper in the active site (binding energy: −5.5 kcal/mol) near the catalytic Cys ^{1 1 2} residue, while 2a binds peripherally (−4.8 kcal/mol). This computational insight corroborates the enhanced antibacterial efficacy of 3a and suggests FabH inhibition as a potential mechanism.

Herein we report a convenient and green synthesis of a new class of phosphonopyrans—2-amino-3-cyano-6-phosphonoethyl-4H-pyrans—through the K₂CO₃-catalyzed reaction of malononitrile with γ-keto-δ-alkenylphosphine oxides. The reaction proceeds under operationally simple and mild conditions, employs a low-cost and an environmentally benign catalyst and ethanol as a green solvent.

The reaction between phosphinylallenes and nitrones efficiently leads to 4‐phosphinylpyrrolidin‐3‐ones. The mechanism of this transformation is investigated theoretically to elucidate the overall pathway and the stereochemical outcome. The process begins with a (3+2) cycloaddition between the nitrone and the allene, delivering an isoxazolidine ylidene intermediate. This intermediate has never been isolated; it spontaneously rearranges to the final 4‐phosphinylpyrrolidin‐3‐one via homolytic cleavage of the NO bond, followed by rotation and CN recombination of the biradical intermediate. The computational results provide valuable insights for achieving diastereo‐ and enantioselective synthesis of 4‐phosphinylpyrrolidin‐3‐ones through careful selection of substituents on the nitrone and allene.

A simple and efficient approach to novel 4H-1,3,2-oxathiaphosphinine-2-sulfide derivatives bearing a phosphonoethyl group at position 6, was accomplished through the reaction of Lawesson’s reagent with γ-keto-δ-alkenylphosphonates and phosphine oxides. This synthetic strategy, which uses easily prepared γ-keto-δ-alkenylphosphonates/phosphine oxides and commercially available Lawesson’s reagent as starting materials, is endowed with several other advantages such as easy operation, good yields and mild reaction conditions.

A general and effective (3 + 2) cycloaddition reaction between nitrones and allenes to synthesize fluoro‐phosphonopyrrolidin‐3‐ones, as well as spiropyrrolidin‐3‐one phosphonates is reported under microwave heating. The products have been isolated in moderate to good yields and exclusively as 4,5‐trans diastereoisomers in all transformations.

Despite their potential in areas such as medicinal chemistry and organic materials, scaffolds in which quinoline and quinoxaline are fused to phosphacycles such as 1,3‐oxaphosphole, 1,3‐azaphosphole, P‐arylated and P‐alkoxylated 2,3‐dihydro‐1,3‐azaphosphole P‐oxides have, to our knowledge, never been reported. In this study we have developed a synthetic approach to [1,3]azaphospholo[4,5‐f]quinolines and ‐quinoxalines from quinolin‐6‐amine and quinoxalin‐6‐amine. These were converted to 5‐phosphanylquino(xa)lin‐6‐amines by regioselective iodination in position 5, cross‐coupling with diethyl phosphite and reduction. Formation of the azaphosphole ring was then achieved by reaction with N,N‐dimethylformamide dimethyl acetal. Attempts at C−H arylation in position 2 did not lead to the desired derivatives but rather to 1‐arylated 2,3‐dihydro‐[1,3]azaphospholo[4,5‐f]quino(xa)line 1‐oxides. Access to 1‐alkoxylated 2,3‐dihydro‐[1,3]azaphospholo[4,5‐f]quinoline 1‐oxides was also developed using as key steps cross‐coupling with ethyl phosphinate formed in situ and the subsequent Kabachnik‐Fields reaction. The resulting tricyclic compounds were finally tested against a panel of disease‐related protein kinases.

Here, we report the intramolecular Heck cross-coupling of 1,3-dienylphosphonates, affording unique and regioselective access to unprecedented benzofused phostone and phostam derivatives. The reactions proceeded under operationally simple and mild conditions with a wide substrate scope.