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.

Graphical abstractNew enantiomerically enriched and racemic α-aminophosphonates are obtained by a solvent-free, one-pot procedure.Download full-size image