127 / 2023-10-12 16:46:03

Novel Synthesis and P-modification of -Amino-2-Hydroxybenzylphosphonates

Aminophosphonates; Diastereoselective synthesis; Ring opening; Salycilaldimines

Phosphorus in Synthetic Chemistry > 3) Syntheses of Chiral organophosphorus compounds

α-Aminophosphonic acids, as structural analogs of α-amino acids achieved through isosteric substitution of the carboxylic group with a phosphonate moiety, have garnered significant attention in the realms of biology, pharmaceuticals, and materials research. In this study, we present novel synthetic approach for the preparation of diastereomeric α-amino-2-hydroxybenzylphosphonates 1. The method relies on the reaction between salicylaldimines and chlorophosphite as detailed in the accompanying Scheme 1. The precipitation of the major diastereomer facilitates its efficient separation and enables the determination of its structure through X-ray analysis.Our investigations reveal that resulting cyclic aminophosphonates 1 exhibit remarkable reactivity toward X-H nucleophiles. Notably, the presence of even trace amounts of moisture in the solvent induces the opening of the five-membered cycle. This intriguing feature creates a facile avenue for transferring the aminophosphonate residue to a variety of molecules encompassing OH or NH functional groups, as depicted in the Scheme 1. Overall, our finding offers new perspectives for the functionalization of biologically and pharmaceutically important molecules with biorelevant aminophosphonate moiety.