Phosphodiester Alkylation with a Quinone Methide.

Despite the wide array of studies involving DNA alkylation and cleavage with quinone methide generating compounds, there have been no reports on the alkylation of phosphodiesters with quinone methides. We have investigated the reaction of dialkyl phosphates with a p-quinone methide in order to determine the potential for alkylation to produce trialkyphosphates. These studies have revealed that a phosphodiester can be alkylated with a p-quinone methide when promoted by a Brønsted acid. The role of the Brønsted acid is to sufficiently activate the p-quinone methide to allow phosphodiester addition to occur. The alkyl substituents of the phosphodiester have been found to effect the reactivity of the dialkyl phosphate under the reaction conditions examined. Equilibrium conversions up to 83% trialkyl phosphate formation have been achieved.