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.