Exocyclic Cleavage in the Alkaline Hydrolysis of Methyl Ethylene Phosphate: Pseudorotation of a Pentavalent Intermediate or Reaction via a Hexavalent Intermediate?

The observation of increasing exocyclic cleavage of methyl ethylene phosphate in alkaline solution was the first evidence for hydrolysis of a phosphate ester by reaction with 2 equiv of hydroxide. Kinetically equivalent mechanisms provide a role for a second hydroxide after the first hydroxide adds to form a pentavalent intermediate. These are (1) proton abstraction, pseudorotation, and exocyclic cleavage and (2) addition to form a hexavalent phosphorus intermediate followed by exocyclic cleavage. The mechanisms can be distinguished by patterns of isotope incorporation from solvent into the product of exocyclic cleavage. The hydrolysis of methyl ethylene phosphate was carried out in D₂0 containing D₂¹⁸0, and the pattern of isotopically shifted phosphorus NMR peaks of ethylene phosphate (and its hydrolysis product hydroxyethyl phosphate) rules out the involvement of hexavalent phosphorus intermediates. The formation of ethylene phosphate via anionic pentavalent intermediates contradicts predictions of a stereoelectronic theory that places great energetic advantage in cleaving the endocyclic ester bond.