Stephen L. Glaser

5-membered cyclic acyl phosphates : A new class of extremely reactive phosphorylating agents

Abstract The reaction of phosgene with the oxyphosphorane made from biacetyl and trimethyl phosphite gives an α-(dimethylphosphato)-β-ketoacid chloride, which undergoes an intramolecular loss of methyl chloride under catalysis; by CuSO4, and yields the first reported 5-membered cyclic acyl phosphate. The acyl phosphate is attacked exclusively at phosphorus by water, alcohols and phenols, at an extraordinarily rapid rate. In contrast, tertiary amines attack only the Me carbon of the exocyclic OMe group of the acyl phosphate to give quaternary ammonium salts of 5-membered cyclic acyl phosphates. These cyclic mixed anhydrides of phosphoric acid are the most powerful phosphorylating agents for oxygen-containing nucleophiles known at present. The end-products of the phosphorylations are phosphotriesters, phosphodiesters, and phosphomonoesters, containing the easily removable acetoinyl group, [(CH3CO)(CH3)CHO]P(O)(OR)(OR′).