Asymmetric synthesis of (R)- and (S)-piperidin-2-yl-phosphonic acid by diastereoselective addition of trialkyl phosphite onto potential iminium salt

Article abstract of DOI:10.1016/S0040-4020(97)00086-0

Two strategies have been developed to synthesize both enantiomers of piperidin-2-yl-phosphonic acid. The first one uses the double condensation of glutaraldehyde with (R)-(-)-phenylglycinol and triethylphosphite to give 2-ethylphosphonate-6-oxazolopiperidine 2 which furnished in few steps (S)-(+)-)piperidin-2yl-phosphonic acid (5) in 58% ee. The second strategy utilizes the 2-cyano-6-oxazolapiperidine synthon 1 which upon treatment with trimethyl phosphite gave 2-cyano-6-oxazaphosphorinane 7 which gave pure (R)-(-)-piperidin-2-yl-phosphonic acid (10) in good overall yield.