Synthesis of selectively 18O-labeled phthalides using water-assisted cyclization

Two selectively 18O-labeled phthalides containing 18O either in the carbonyl (i.e., C18O) or in the alkoxy group (i.e., OC–18O) of the lactone ring were prepared in good yields (ca. 70%) from the corresponding methyl 2-(bromomethyl)benzoate and its selectively C18O labeled derivative, respectively, using water-assisted cyclization. The reaction mechanism involving formation of a cyclic carboxonium bromide and its water-assisted decomposition to the lactone is proposed.