Synthesis of isoindolinone phosphonates and their related derivatives by multicomponent reaction

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…By using dialkyl phosphites 483 , Bálint’s research group has developed a catalyst-free MW assisted synthesis of isoindolin-1-one-3-phosphonates 485 . This reaction was studied both under continuous flow MW conditions and using P-stereogenic secondary phosphine oxides 484 at 25 °C in acetonitrile, allowing to obtain the desired compounds with very good yields (Scheme , conditions iv and v). − This reaction proceeds through the formation of the imine resulting from the condensation of the amine and the aldehyde. Subsequently, an attack of the phosphorus nucleophile took place, which is facilitated by the protonation of the imine with the adjacent carboxylic acid, and the final compound is obtained after the intramolecular nucleophilic attack of the amine to the carbonyl carbon.…”