Endocyclic cleavage in the alkaline hydrolysis of the cyclic phosphonate methyl propylphostonate: Dianionic intermediates and barriers to pseudorotation

Article abstract of DOI:10.1021/ja00015a027

The hydrolysis of methyl propylphostonate in basic solutions leads exclusively to products resulting from cleavage of the internal ester linkage. On the basis of the mechanism of reaction deduced from the study of cyclic phosphate triesters, it is expected that the addition of hydroxide generates a five-coordinate phosphorus intermediate that reacts with a second hydroxide to give a dianion. Stereoelectronic properties of this dianionic intermediate prevent pseudorotation and lead to the exclusive formation of the endocyclic cleavage product, methyl (γ-hydroxypropyl)phosphonate. These results are consistent with a semiempirical formulation developed by Holmes. Ab initio calculations on related gas-phase systems, aimed at explaining the complex catalytic pathway of ribonuclease, do not suggest the consistent patterns observed in the present study and related experimental observations. Thus, the effects of solvation on reactivity patterns of cyclic phosphate esters are very significant.