The surprising reaction of (chloro- and methanesulfonyloxy)(phenyl)methylphosphonates and -(phenyl)methylphosphine oxides with potassium diphenylphosphide followed by oxidation.

α-Hydroxyphosphonates and α-hydroxyphosphine oxides are important intermediates for additional biologically active species. While (hydroxy(phenyl)methyl)(diphenyl)phosphine oxide did not even undergo chlorination with thionyl chloride, the reaction of diethyl chloro(phenyl)methylphosphonate with potassium diphenylphosphide followed by oxidation with hydrogen peroxide resulted in the expected bis(>P(O)-functionalized) product only as a minor component. The similar reaction of the analogous (methanesulfonyloxy)(phenyl)methyl derivative afforded a mixture of a diethyl (diethoxyphosphonyl)(phenyl)methyl phosphate, a diethyl (diphenylphosphinyl)(phenyl)methyl phosphate, and a ((diphenylphosphinyl)(phenyl)methyl) diphenylphosphinate. The formation of the unexpected products was explained assuming rearrangements and reversible formation of the hydroxymethylene-bis(>P(O)-functionalized) intermediate. Contrary to the earlier experiences, the reaction of ((methanesulfonyloxy)(phenyl)methyl)(diaryl)phosphine oxides with potassium diphenylphosphide followed by oxidation took place in a clear-cut manner providing, with one exception, the corresponding α-phosphinylated α-hydroxyphosphine oxides that could also be synthesized by direct phosphinylation of the starting α-hydroxyphosphine oxide. Cell viability assays performed on U266 myeloma cells revealed concentration-dependent antiproliferative effects of the synthesized compounds on U266 myeloma cells, highlighting the key role of the phosphinoyloxy moiety in the cytotoxic activity, which may be enhanced further by 4-methyl groups in the P-phenyl rings.