A method for the generation/in situ hetero-Diels–Alder cycloaddition of a trisubstituted ortho-quinone methide (o-QM) is described. Heating of ortho-hydroxybenzylamines was found to be a more effective strategy for the formation of o-QMs than use of the corresponding N-substituted quaternary salts hitherto employed. This method was used to synthesise the spiroketal core of the rubromycins.