Synthesis of hydroxyphosphonic acid derivatives

Abstract

The synthesis of α-hydroxyphosphonates by the reaction between dialkyl phosphites and aldehydes using various catalysts such as triethylamine, alumina, titanium isoproproxide, and lithium aluminium hydride were studied. The use of lithium aluminium hydride as catalyst resulted in the desired products in moderate to high yields (43-84%). The asymmetric synthesis of α – hydroxyphosphonates by asymmetric hydrophosphonylation reaction of aromatic aldehyde with dialkyl phosphites in the presence of a catalytic amount of complexes of lithium aluminium hydride and chiral ligands was carried out. The ligands of interest are chiral Schiff’s base, peptide Schiff’s base, and N- salicyl –β- aminoalcohol ligands. The reaction of aldehydes and dialkyl phosphites in the presence of Li – Al- N- salicyl –β- aminoalcohol complexes proceeded efficiently to give the corresponding α – hydroxyphosphonates in moderate yields (50 – 75%) and moderate enantioselectivity (32 – 70 % ee). The enantiomeric excess was observed by chiral gas chromatography. The bulkiness of substituents on the salicyl and β- amino alcohol moiety plays a significant role in the induction of enantioselectivities. In addition, the aliphatic aldehydes gave product in higher enantiomeric excess than aromatic aldehydes.