A general synthetic approach to alpha-hydroxy phosphoryl compounds

A general synthetic way for the preparation of a large variety of cc-hydroxy phosphoryl compounds is here reported. In our approach, trialkyl phosphite is added in equimolar amount, at room temperature and under strong acidic conditions (HCl gas), to the corresponding carbonyl compound dissolved in anhydrous dioxane. The reaction is quite exothermic and cooling is often needed; 10-15 min reaction time is sufficient in order to assure almost quantitative yields in the desired product, which can be easily isolated as a white pure solid by concentration of the reaction mixture. The reaction works in an excellent way with all kind of aliphatic, aromatic and heteroaromatic aldehydes. The alpha-hydroxy phosphonates obtained were fully characterized by H-1- and P-31-NMR, by FAB-MS and IR spectroscopy. When o-carboxybenzaldehyde was used as a reagent, cyclic dialkyl phthalide-3-phosphonates were obtained in very good yields (greater than or equal to 90%).