Stereoelectronic Effects in the Hydrolysis of Ethyl and Methyl Ethylene Phosphates

Article abstract of DOI:10.1021/jo00197a041

Ethyl and methyl ethylene phosphates 1 are shown to hydrolyze with complete endocyclic cleavage between pH 8 and 15 to yield ethyl and methyl 2-hydroxyethyl phosphates 3, respectively.A much slower reaction involving recyclization of the methyl hydroxyethyl phosphate 3 to form ethylene phosphate 4, which undergoes rapid further hydrolysis to 2-hydroxyethyl phosphate 5, is conveniently monitored by 31P NMR.The strained cyclic five-membered ring phosphate triester 1 reacts 10⁸- to 10¹²-fold faster than its strain-free initial diester product 3 via a common phosphorane intermediate/transition state 2.When 1 is hydrolyzed in H2¹⁸O, only mono 18O-labeled ester 3 is formed but no doubly 18O-labeled 3 is detected.All reactions proceed with complete P-O cleavage as monitored by 18O isotope shifts on the 31P signals of the products.These results are consistent with the stereoelectronic effect, and a mechanism involving a hexacoordinate phosphorus intermediate can be ruled out.