The oxidative cleavage of the dihydropyran ring of 1-aryl-isochroman derivatives was carried out for the first time under green chemistry conditions in the presence of the Trametes villosa laccase/1-hydroxybenzotriazole system in buffered water/1,4-dioxane and buffered water/dimethyl carbonate as reaction media. The corresponding oxidation products [2-(2-hydroxyethyl)benzophenone derivatives] were obtained in different yields depending on the substituents on phenyl and isochroman rings. These compounds are useful intermediates for the synthesis of anticancer agents and neuroprotective drugs.