Cyclic chlorophosphites as scaffolds for the one-pot synthesis of α-aminophosphonates under solvent-free conditions

New α-aminophosphonates of the type (OCH2CMe2CH2O)P(O)CH(NHCO2R)(R′) [6a–i, 7a–e, and 8a–c] have been synthesized in high yields by a three-component reaction using (OCH2CMe2CH2O)PCl (3), benzamide (or urethane or benzyl carbamate), and an aldehyde without using any catalyst under solvent-free conditions. This route can be readily adapted for bis-aminophosphonates as well as optically active binaphthoxy α-aminophosphonates; it also tolerates the phenolic –OH group as shown by the synthesis of hydroxy functionalized aminophosphonates. Partial hydrolysis of compounds 7a–d leads to products in which the phosphorinane ring is cleaved first. Compounds (OCH2CMe2CH2O)P(O)CH[NHC(O)Ph](9-anthryl) (6f) and optically pure (R,S)-(−)-(C20H12O2)P(O)CH(NHCO2Et)(Ph) (14a) were characterized by X-ray crystallography.