Phosphodiester alkylation with a quinone methide

Despite the wide array of studies involving DNA alkylation and cleavage wit h quinone methide generating compounds, there have been no reports on the a lkylation of phosphodiesters with quinone methides. We have investigated th e reaction of dialkyl phosphates with a p-quinone methide in order to deter mine the potential for alkylation to produce trialkyphosphates. These studi es have revealed that a phosphodiester can be alkylated with a p-quinone me thide when promoted by a Bronsted acid. The role of the Bronsted acid is to sufficiently activate the p-quinone methide to allow phosphodiester additi on to occur. The alkyl substituents of the phosphodiester have been found t o effect the reactivity of the dialkyl phosphate under the reaction conditi ons examined. Equilibrium conversions up to 83% trialkyl phosphate formatio n have been achieved.