An efficient synthesis of cis -4-hydroxyphosphonic and cis -4-hydroxyphosphinic analogs of pipecolic acid from cyclic enaminones

An expedient synthetic entry to cis -4-hydroxyphosphonic and cis -4-hydroxyphosphinic analogs of cis -4-hydroxypipecolic acid is presented in this paper. The main feature of this methodology is the highly regioselective addition of silyl phosphites or phosphonites to cyclic 1-benzyloxycarbonyl enaminones. Interestingly, the hydride reduction of the resulting 2-phospho-4-oxopiperidine proceeds with high diastereofacial preference using NaBH 4 . In the last step, the cleavage of N -Cbz group under hydrogenolysis followed by the hydrolysis of the phosphonate or phosphinate functionalities, led to the target cis -4-hydroxyphosphonic and cis -4-hydroxyphosphinic acids, respectively.